Topical Treatments For Chronic Plaque Psoriasis (Review)

Topical treatments for chronic plaque psoriasis (Review)
Mason AR, Mason J, Cork M, Dooley G, Edwards G
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2009, Issue 2 http://www.thecochranelibrary.com
Topical treatments for chronic plaque psoriasis (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Vitamin D analogues vs. placebo, Outcome 1 IAGI. . . . . . . . . . . . . . Analysis 1.2. Comparison 1 Vitamin D analogues vs. placebo, Outcome 2 TSS. . . . . . . . . . . . . . Analysis 1.3. Comparison 1 Vitamin D analogues vs. placebo, Outcome 3 PASI. . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Vitamin D analogues vs. placebo, Outcome 4 PAGI. . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Vitamin D analogues vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). Analysis 1.6. Comparison 1 Vitamin D analogues vs. placebo, Outcome 6 Total withdrawals. . . . . . . . . Analysis 1.7. Comparison 1 Vitamin D analogues vs. placebo, Outcome 7 Withdrawals due to adverse events. . . . Analysis 1.8. Comparison 1 Vitamin D analogues vs. placebo, Outcome 8 Withdrawals due to treatment failure. . . Analysis 1.9. Comparison 1 Vitamin D analogues vs. placebo, Outcome 9 Adverse events (local). . . . . . . . Analysis 1.10. Comparison 1 Vitamin D analogues vs. placebo, Outcome 10 Adverse events (systemic). . . . . . Analysis 2.1. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 1 IAGI. . . . . . . . . . . . . Analysis 2.2. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 2 TSS. . . . . . . . . . . . . Analysis 2.3. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 3 PASI. . . . . . . . . . . . . Analysis 2.5. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.6. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 6 Total withdrawals. . . . . . . . . Analysis 2.7. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 7 Withdrawals due to adverse events. . . Analysis 2.8. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 8 Withdrawals due to treatment failure. . Analysis 2.9. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 9 Adverse events (local). . . . . . . Analysis 2.10. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 10 Adverse events (systemic). . . . . Analysis 3.1. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 1 IAGI. . . . . . . . . . . Analysis 3.2. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 2 TSS. . . . . . . . . . . . Analysis 3.4. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 4 PAGI. . . . . . . . . . . Analysis 3.5. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.6. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 6 Total withdrawals. . . . . . . Analysis 3.7. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 7 Withdrawals due to adverse events. Analysis 3.8. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 8 Withdrawals due to treatment failure. Analysis 3.9. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 9 Adverse events (local). . . . . . Analysis 3.10. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 10 Adverse events (systemic). . . . Analysis 4.1. Comparison 4 Dithranol vs. placebo, Outcome 1 IAGI. . . . . . . . . . . . . . . . . . Analysis 4.2. Comparison 4 Dithranol vs. placebo, Outcome 2 TSS. . . . . . . . . . . . . . . . . . Analysis 4.5. Comparison 4 Dithranol vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . Analysis 4.6. Comparison 4 Dithranol vs. placebo, Outcome 6 Total withdrawals. . . . . . . . . . . . .
1 1 2 2 3 5 7 7 12 13 15 45 47 48 49 69 268 302 304 306 307 309 311 313 315 317 319 321 323 325 327 329 331 333 335 337 339 340 341 342 343 344 345 347 348 349 349 350 350
i
Analysis 4.7. Comparison 4 Dithranol vs. placebo, Outcome 7 Withdrawals due to adverse events. . . . . . . . Analysis 4.8. Comparison 4 Dithranol vs. placebo, Outcome 8 Withdrawals due to treatment failure. . . . . . . Analysis 4.9. Comparison 4 Dithranol vs. placebo, Outcome 9 Adverse events (local). . . . . . . . . . . . Analysis 4.10. Comparison 4 Dithranol vs. placebo, Outcome 10 Adverse events (systemic). . . . . . . . . . Analysis 5.2. Comparison 5 Tazarotene vs. placebo, Outcome 2 TSS. . . . . . . . . . . . . . . . . . Analysis 5.5. Comparison 5 Tazarotene vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . Analysis 5.6. Comparison 5 Tazarotene vs. placebo, Outcome 6 Total withdrawals. . . . . . . . . . . . . Analysis 5.7. Comparison 5 Tazarotene vs. placebo, Outcome 7 Withdrawals due to adverse events. . . . . . . Analysis 5.8. Comparison 5 Tazarotene vs. placebo, Outcome 8 Withdrawals due to treatment failure. . . . . . Analysis 5.9. Comparison 5 Tazarotene vs. placebo, Outcome 9 Adverse events (local). . . . . . . . . . . . Analysis 5.10. Comparison 5 Tazarotene vs. placebo, Outcome 10 Adverse events (systemic). . . . . . . . . . Analysis 6.1. Comparison 6 Other treatment vs. placebo, Outcome 1 IAGI. . . . . . . . . . . . . . . Analysis 6.2. Comparison 6 Other treatment vs. placebo, Outcome 2 TSS. . . . . . . . . . . . . . . . Analysis 6.3. Comparison 6 Other treatment vs. placebo, Outcome 3 PASI. . . . . . . . . . . . . . . Analysis 6.4. Comparison 6 Other treatment vs. placebo, Outcome 4 PAGI. . . . . . . . . . . . . . . Analysis 6.5. Comparison 6 Other treatment vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). Analysis 6.6. Comparison 6 Other treatment vs. placebo, Outcome 6 Total withdrawals. . . . . . . . . . . Analysis 6.7. Comparison 6 Other treatment vs. placebo, Outcome 7 Withdrawals due to adverse events. . . . . Analysis 6.8. Comparison 6 Other treatment vs. placebo, Outcome 8 Withdrawals due to treatment failure. . . . Analysis 6.9. Comparison 6 Other treatment vs. placebo, Outcome 9 Adverse events (local). . . . . . . . . . Analysis 6.10. Comparison 6 Other treatment vs. placebo, Outcome 10 Adverse events (systemic). . . . . . . . Analysis 7.1. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 1 IAGI. . . . . . . . . Analysis 7.2. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 2 TSS. . . . . . . . . Analysis 7.3. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 3 PASI. . . . . . . . . Analysis 7.4. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 4 PAGI. . . . . . . . Analysis 7.5. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.6. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 6 Total withdrawals. . . . Analysis 7.7. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.8. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 7.9. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 9 Adverse events (local). . . Analysis 7.10. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 10 Adverse events (systemic). Analysis 8.2. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 2 TSS. . . . . . . Analysis 8.3. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 3 PASI. . . . . . . Analysis 8.5. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.6. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 6 Total withdrawals. . . Analysis 8.7. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.8. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 8.9. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 9 Adverse events (local). Analysis 8.10. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 10 Adverse events (systemic). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.1. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 1 IAGI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.2. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 2 TSS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.3. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 3 PASI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
351 351 352 352 353 353 354 354 355 355 356 357 360 363 366 369 372 376 380 384 388 391 393 395 396 398 400 402 404 406 408 410 410 411 411 412 412 413 413 414 414 415
ii
Analysis 9.5. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . Analysis 9.6. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 6 Total withdrawals. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.7. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.9. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 9 Adverse events (local). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 9.10. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 10 Adverse events (systemic). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 10.1. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 1 IAGI. . . . . . . . . . . . Analysis 10.2. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 2 TSS. . . . . . . . . . . . . Analysis 10.3. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 3 PASI. . . . . . . . . . . . Analysis 10.4. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 4 PAGI. . . . . . . . . . . . Analysis 10.5. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 10.6. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 6 Total withdrawals. . . . . . . . Analysis 10.7. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 7 Withdrawals due to adverse events. . Analysis 10.8. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 8 Withdrawals due to treatment failure. Analysis 10.9. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 9 Adverse events (local). . . . . . . Analysis 10.10. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 10 Adverse events (systemic). . . . Analysis 11.1. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 1 IAGI. . . . . . . . . . . . . Analysis 11.3. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 3 PASI. . . . . . . . . . . . . Analysis 11.4. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 4 PAGI. . . . . . . . . . . . . Analysis 11.5. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 11.6. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 6 Total withdrawals. . . . . . . . . Analysis 11.7. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 7 Withdrawals due to adverse events. . . Analysis 11.8. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 8 Withdrawals due to treatment failure. . Analysis 11.10. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 10 Adverse events (systemic). . . . . Analysis 12.1. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 1 IAGI. . . . . . . . . Analysis 12.2. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 2 TSS. . . . . . . . . Analysis 12.3. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 3 PASI. . . . . . . . . Analysis 12.5. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.6. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 6 Total withdrawals. . . . . Analysis 12.7. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.8. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 12.9. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 9 Adverse events (local). . . Analysis 12.10. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 10 Adverse events (systemic). Analysis 13.1. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 1 IAGI. . . . . . Analysis 13.2. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 2 TSS. . . . . . Analysis 13.3. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 3 PASI. . . . . . Analysis 13.5. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.6. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 6 Total withdrawals. Analysis 13.7. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.8. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 13.9. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 9 Adverse events (local).
416 416 417 418 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 448 450 452 454 455 456 457
iii
Analysis 13.10. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 10 Adverse events (systemic). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.1. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 1 IAGI. . . . . . . . Analysis 14.3. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 3 PASI. . . . . . . . Analysis 14.4. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 4 PAGI. . . . . . . . Analysis 14.5. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.6. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 6 Total withdrawals. . . . Analysis 14.7. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 7 Withdrawals due to adverse events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.8. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 14.9. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 9 Adverse events (local). . Analysis 14.10. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 10 Adverse events (systemic). Analysis 15.1. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 1 IAGI. . . . . . . . . . . . Analysis 15.2. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 2 TSS. . . . . . . . . . . . Analysis 15.3. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 3 PASI. . . . . . . . . . . . Analysis 15.4. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 4 PAGI. . . . . . . . . . . . Analysis 15.5. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 15.6. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 6 Total withdrawals. . . . . . . . Analysis 15.7. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 7 Withdrawals due to adverse events. . Analysis 15.8. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 8 Withdrawals due to treatment failure. Analysis 15.9. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 9 Adverse events (local). . . . . . Analysis 15.10. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 10 Adverse events (systemic). . . . Analysis 16.1. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 1 IAGI. . . . . . . . . . . . Analysis 16.3. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 3 PASI. . . . . . . . . . . . Analysis 16.5. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 16.6. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 6 Total withdrawals. . . . . . . . Analysis 16.7. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 7 Withdrawals due to adverse events. . Analysis 16.8. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 8 Withdrawals due to treatment failure. Analysis 16.9. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 9 Adverse events (local). . . . . . . Analysis 16.10. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 10 Adverse events (systemic). . . . Analysis 17.2. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 2 TSS. . . . . . . . . . . . Analysis 17.5. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 17.10. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 10 Adverse events (systemic). . . Analysis 18.1. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 1 IAGI. . . . . . . . . . Analysis 18.2. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 2 TSS. . . . . . . . . . Analysis 18.3. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 3 PASI. . . . . . . . . . Analysis 18.4. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 4 PAGI. . . . . . . . . . Analysis 18.5. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 18.6. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 6 Total withdrawals. . . . . . Analysis 18.7. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 7 Withdrawals due to adverse events. Analysis 18.8. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 8 Withdrawals due to treatment failure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 18.9. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 9 Adverse events (local). . . . Analysis 18.10. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 10 Adverse events (systemic). . ADDITIONAL TABLES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . APPENDICES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
458 459 459 460 460 461 461 462 462 463 464 465 466 467 468 469 470 470 471 472 473 474 475 476 476 477 477 478 478 479 479 480 481 482 483 484 485 486 488 489 491 492 544 561
iv
CONTRIBUTIONS OF AUTHORS . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW INDEX TERMS . . . . . . . . . . . . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
. . . . .
562 562 563 563 564
[Intervention Review]
Topical treatments for chronic plaque psoriasis

Anne R Mason1 , James Mason2 , Michael Cork3 , Gordon Dooley4 , Gladys Edwards5
1 Centre for Health Economics, University of York, York, UK. 2 School of Medicine and Health, Durham University, Queens Campus, Stockton-on-Tees, UK. 3 Academic Unit of Biomedical Genetics-Dematology, School of Medicine & Biomedical Sciences, The University of Shefeld, Shefeld, UK. 4 Update Software Ltd, Oxford, UK. 5 Psoriasis Association, Northampton, UK
Contact address: Anne R Mason, Centre for Health Economics, University of York, Alcuin A Block, Heslington, York, YO10 5DD, UK. arm10@york.ac.uk. Editorial group: Cochrane Skin Group. Publication status and date: New, published in Issue 2, 2009. Review content assessed as up-to-date: 14 December 2008. Citation: Mason AR, Mason J, Cork M, Dooley G, Edwards G. Topical treatments for chronic plaque psoriasis. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD005028. DOI: 10.1002/14651858.CD005028.pub2. Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT Background Chronic plaque psoriasis is the most common type of psoriasis and is characterised by redness, thickness and scaling. First line management of chronic plaque psoriasis is with topical treatments, including vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids. Objectives To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis with placebo; to compare vitamin D analogues with other topical treatments. Search methods The Cochrane Skin Groups Trials Register was searched (2004/12). To update an unpublished 2002 review we also searched CENTRAL in The Cochrane Library (Issue 1,2005); MEDLINE (to 2005/02); EMBASE (to 2005/08); Science Citation Index (to 2005); Biosis (to 2005); Dissertation Abstracts (all publication years); Inside Conferences (all publication years); SIGLE (to 2005); National Research Register (all projects with a start date of 2001 to 2005); metaRegister of Current Controlled Trials. Selection criteria Randomised trials comparing treatments against placebo or against vitamin D analogues in people with chronic plaque psoriasis. Data collection and analysis One author extracted study data and assessed study quality. A second author checked these data. We routinely contacted triallists and companies for missing data. We extracted data on withdrawals and adverse events. Main results The review included 131 RCTs with 21,448 participants. Vitamin D was signicantly more effective than placebo, although there was a wide variation in effect size with the standardised mean difference (SMD) ranging from -0.82 (95% CI -1.34 to -0.29) to -1.90 (95% CI -2.09 to -1.71). With one exception, all corticosteroids performed better than placebo, with potent corticosteroids (SMD: -0.95 (95% CI: -1.11 to -0.80; I: 61.1%; 17 studies; 2386 participants)) having smaller benets than very potent corticosteroids (SMD: -1.29 (95% CI: -1.45 to -1.13; I: 53.2%; 11 studies; 1571 participants)). Dithranol and tazarotene performed better than placebo. HeadTopical treatments for chronic plaque psoriasis (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 1
to-head comparisons of vitamin D against potent or very potent corticosteroids found no signicant differences. However, combined treatment with vitamin D /corticosteroid performed signicantly better than either vitamin D alone or corticosteroid alone. Vitamin D performed better than coal tar, but ndings relative to dithranol were mixed. Potent corticosteroids were less likely than vitamin D to cause local adverse events. No comparison of topical agents found a signicant difference in systemic adverse effects. Authors conclusions Corticosteroids perform as well as vitamin D analogues and are associated with a lower incidence of local adverse events. Further research is required to inform long-term maintenance treatment.
PLAIN LANGUAGE SUMMARY Skin treatments for chronic plaque psoriasis Chronic plaque psoriasis is the most common type of psoriasis. Although any part of the body may be affected, the most commonly affected sites are the elbows, knees and scalp. Topical treatments (i.e. treatments applied to the skin) are usually tried rst. These include vitamin D products, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and vitamin A products. As chronic plaque psoriasis is a long-term condition, it is important to nd out which treatments work best and what adverse-effects they have. The evidence was based on 131 studies that included 21,448 people. Studies were typically about 6 weeks long, but this ranged from 1 to 24 weeks. Vitamin D products were found to work better than placebo (the base cream or ointment). Potent (strong, e.g. betamethasone dipropionate) and very potent (very strong, e.g. clobetasol propionate) topical corticosteroids were also effective. Dithranol and tazarotene also worked better than placebo. Their effects were similar to vitamin D products. Some studies compared vitamin D products directly with potent or very potent corticosteroids. These products had similar effects when applied to the body, but corticosteroids appeared to work better for scalp psoriasis. However, treatment that combined vitamin D with a potent corticosteroid was more effective than either vitamin D alone or topical potent corticosteroid alone. Vitamin D products performed better than coal tar, but studies found different results when comparing vitamin D with dithranol. Vitamin D products were more effective when covered (occlusion), or when applied twice-daily rather than once-daily. Potent corticosteroids were less likely than vitamin D to cause local adverse events, such as skin irritation, and people were therefore more likely to stop using vitamin D products. Tazarotene was more likely to cause local adverse events than placebo, and people with psoriasis were therefore more likely to stop using it. When studies examined whether topical treatments had effects within the body (systemic adverse events), we found no difference between placebo and any other treatment. However, this may be because many trials did not properly assess systemic adverse events rather than because there really was no difference.
There are very few long-term studies that can help doctors and people with psoriasis decide on the best way to treat this chronic condition.
BACKGROUND
Psoriasis comprises multiple phenotypes, and may be localised (e.g. to the skin fold areas (inverse psoriasis), or to the palms or soles) or widespread. Types of widespread psoriasis include guttate, generalised pustular and erythrodermic (Grifths 2007). Chronic plaque psoriasis may be localised or widespread and accounts for 90% of psoriasis cases (Grifths 2007); it is characterised by red patches of thickened skin (plaques) covered in silver scales (Figure
2
Description of the condition

Psoriasis is a chronic inammatory skin disease with a prevalence ranging from between 1 and 2% in the UK and northern European populations (Hellgren 1967; Krueger 1984) to 0.1 to 0.3% in the Far East (Simons 1949) and China (Yui Yip 1984).
1). Any area of the body may be affected, but the main areas are the knees, elbows, lower back and scalp. There is a wide spectrum of disease severity from a single plaque to involvement of more than 90% of the skin surface. Psoriasis may be classied as mild, moderate or severe, although these categories are difcult to dene precisely (Krueger 2000). The cutaneous (skin) manifestations of psoriasis are accompanied by psoriatic arthritis in 5 to 30% of cases (Barisic-Drusko 1994; Krueger 1984; Salvarani 1995; Zanolli 1992). The wide variation in reported prevalence of psoriatic arthritis may be reduced by recent improvements in the classication criteria (Taylor 2006). Psoriasis occurs in 5% of people with Crohns disease (Lee 1990). Figure 1. Chronic Plaque Psoriasis Source: Dermis Dermatology Atlas Online (used with permission)
Causes Disease progression is complex and appears to be inuenced by many factors including local trauma, infections, certain drugs (such as beta-blockers, lithium, chloroquine and NSAIDs), the duration of antipsoriatic treatments, endocrine factors, sunlight,
alcohol, smoking and stress (Tagami 1997). The skin lesions of psoriasis are shown in Figure 2 and are characterised by cells multiplying too quickly (epidermal hyperproliferation), cells not maturing normally (abnormal keratinocyte differentiation) and the presence of cells which cause inammation (a lymphocyte inamma3
tory inltrate) (Barker 1991; Grifths 2003; Stern 1997). Psoriasis is now recognised as an immune-mediated disorder, with tumour necrosis factor alpha (TNF ), dendritic cells and T-cells all contributing to its pathogenesis (Grifths 2007a). Several genes interact with environmental factors to induce the development of psoriasis and different combinations of changes in several genes and environmental factors can produce the same clinical picture of psoriasis (Bhalerao 1998; Brandrup 1978; Farber 1974; Lomholt 1963; Willan 1808). At least nine chromosomal psoriasis susceptibility loci have been identied (Grifths 2007a). The strongest association and linkage is to a locus within the major histocompatibil-
ity complex, the area affecting immune response (Henseler 1992; Russell 1972; Svejgaard 1974; Tazi-Ahnini 1999a; Tazi-Ahnini 1999b; Trembath 1997). Other linkage studies have reported linkage to 4q and 17q (Matthews 1996; Tomfohrde 1994) and to 16q and 20q (Nair 1997; Trembath 1997). Proinammatory CD4positive T helper cells produce interferon-gamma (Th1) or interleukin (IL)-17 (Th17). These cells interact with dendritic cells, macrophages, mast cells, and neutrophils, causing inammation (Ghoreschi 2007). However, the genes, or combination of genes, within these regions that contribute to the development of psoriasis have not yet been established.
Figure 2. The Epidermis in the skin of people with and without psoriasis
Impact Until identied as a single disease by von Hebra in 1841, psoriasis was thought to be a variant of leprosy and regarded as contagious (de Jong 1997). The misconception may persist: in a survey of people with psoriasis in 1997, almost three-quarters of respondents reported that others thought their condition was contagious and a similar proportion feared swimming and taking part in sporting activities (Watts 1998). Psoriasis can lead to social isolation (van de Kerkhof 1997a), stigmatisation (Gupta 1998; van de Kerkhof 1997a) and fear of other peoples reactions, adversely affecting the quality of daily life (Finlay 1994; Finlay 1995a; Finlay 1995b; Finlay 2001; McKenna 2003; Ortonne 2000; Richards 2003; Stern 1995). Psychological distress induced by psoriasis may also impair the response to treatment (Fortune 2003).
2008). Transactivation appears to be involved in the mediation of some adverse reactions, such as skin atrophy. Immunomodulation seems to be the result of GC mediated transrepression, that is, silencing of pro-inammatory genes such as for TNF . Nonsteroidal GC receptor ligands (selective GC receptor agonists) have recently been identied and may reduce the side-effects of GC without loss of immunosuppressive effects (Bos 2008). There is evidence that the naturally occurring active metabolite of vitamin D, calcitriol (1a25-dihydroxyvitamin D3) (Langner 1996), and two synthetic vitamin D analogues, calcipotriol (Kragballe 1988; Kragballe 1989; Staberg 1989a) and tacalcitol (1a24-dihydroxyvitamin D3) (Baadsgaard 1995; van de Kerkhof 1996a), are effective when applied topically in psoriasis (Mason 2002a). These agents bind to vitamin D receptors (VDR), which in turn bind to vitamin D responsive elements (VDRE) in multiple genes. Switching on (transactivation of ) these genes inhibits the multiplication of cells and stimulates their differentiation (Figure 2). VDRs also suppress the inammatory component of psoriasis by inhibiting the production of pro-inammatory cytokines (small proteins that affect cell-cell interaction) such as interleukin1 (IL-1). Vitamin D analogues all have the potential to induce abnormally high levels of calcium in the blood serum (hypercalcaemia) and urine (hypercalciuria). Although calcipotriol ointment causes no elevation of total serum calcium when used at the recommended dose of 100 g per week (Mortensen 1993), there are signicant elevations in both serum and urinary calcium when the dose is increased to 300 g per week (Bourke 1993a; Bourke 1994). Topical vitamin D analogues are cosmetically acceptable, are not known to cause skin atrophy and are not usually associated with rebound when therapy is discontinued. However, at least 25% of people have little or no response to topical vitamin D analogues (Holick 1996; Mee 1998). Urea or salicylic acid may be used to reduce thickness and scaling of the skin; combination with other products can improve their absorption. However, these can also irritate the skin. Topical immunosuppressants, such as methotrexate, and topical macrolactams, such as tacrolimus, are relatively new treatments and their effectiveness, tolerability and longer-term effects are less clear than with the more established products. This review will also consider combination products involving any of the above treatments. There are three published Cochrane reviews of interventions for psoriasis. The review by Owen 2000 assessed the impact of antistreptococcal interventions for guttate and chronic plaque psoriasis. The review found that although both antibiotics and tonsillectomy have frequently been advocated for patients with recurrent guttate psoriasis or chronic plaque psoriasis, there is to date no good evidence that either intervention is benecial. Chalmers 2000 reviewed all treatments, excluding antistreptococcal inter-
Description of the intervention

Treatment of psoriasis must always be appropriate to its severity and importance to that individual: it should never be more unpleasant, intolerable or dangerous than the disease itself (Camp 1992). Topical treatments include vitamin D analogues, topical corticosteroids, tar-based preparations, dithranol, salicylic acid and topical retinoids (Baadsgaard 1995; Corbett 1976; Fredriksson 1980; Goeckerman 1931; Ingram 1953; Kragballe 1988; Kragballe 1989; Langner 1996; Staberg 1989a; Unna 1916; van de Kerkhof 1996a), but there is no evidence-based treatment ladder by which to sequence treatments (Van de Kerkhof 2008). Emollients are generally used in a supportive role as an addition to topical treatments, to normalise hyperproliferation, differentiation, and to exert anti-inammatory effects (Fluhr 2008). The two classes of topical treatment for psoriasis most commonly prescribed in developed countries are vitamin D analogues and topical corticosteroids because they are considered more cosmetically acceptable than tar and dithranol preparations (Baadsgaard 1995; Kragballe 1988; van de Kerkhof 1996a). Topical corticosteroids are available in four potencies, mild, moderate, potent and very potent, assessed using the vasoconstrictor assay (BMA 2007). The benet of topical steroids is that in cream formulations they are easy to apply, cosmetically acceptable, do not stain the skin and rarely cause irritation. There are several adverse effects of corticosteroids including cutaneous atrophy, rebound after discontinuation of treatment and decreasing response to the drug (tachyphylaxis) (du Vivier 1975; Lee 1998; Kao 2003). Glucocorticoids (GC) exert their effects either via interaction with cell membranes (non genomic effects) or via interaction with intracellular uid in GC receptors and downstream with the genome (genomic effects). The genomic effects can be divided into transrepression (inhibition of synthesis of regulatory proteins) and transactivation (induction of the synthesis of regulatory proteins) (Bos
ventions, for guttate psoriasis. The review identied only one relevant trial and no evidence of the effectiveness of any topical interventions. The review by Chalmers 2006 assessed interventions, including topical treatments, for chronic palmoplantar pustulosis (a disease that is closely related to psoriasis and used to be considered a variant of psoriasis). Topical steroids under hydrocolloid occlusion were found to be effective in inducing remission (Chalmers 2006). In addition, six protocols of Cochrane reviews have been published, covering methotrexate (Harries 2005), traditional Chinese herbs (Wu 2005), fumaric acid esters (Harries 2005a), oral retinoids (Janjua 2006), biologics (Angus 2006) and interventions for nail psoriasis (Velema 2009).
Authors conclusions Under Primary outcome measures, we report ndings for each of the 18 analyses (including sensitivity analyses). We also do this under Secondary outcome measures for subsections (a) and (b).
OBJECTIVES
To compare the effectiveness, tolerability and safety of topical treatments for chronic plaque psoriasis, relative to placebo and to similarly compare vitamin D analogues with other topical treatments.
Why it is important to do this review

Chronic plaque psoriasis is a condition for which there is no known cure and currently available treatments may only temporarily clear the skin (Bonifati 1998); Grifths 2004). Clinical practice varies between and within different countries. By focusing on topical treatments for psoriasis, either as monotherapy or in combination, this review will assesses the relative effectiveness, tolerability and safety of these treatments and so helps to determine how best to induce remission and delay recurrence in people receiving topical treatment. Table 1 provides a list of acronyms used in the review.
METHODS
Criteria for considering studies for this review
Structure of the Review The structure of the review is provided to facilitate navigation: Objectives Methods Results Description of the studies Risk of bias in the included studies Effects of the interventions (1) Primary outcome measures (a) Investigator assessment of overall global improvement (IAGI) (b) Total severity scores (TSS) (c) Psoriasis area and severity index (PASI) (d) Patient assessment of overall global improvement (PAGI) (e) Combined endpoint (IAGI / TSS / PASI / PAGI) (2) Secondary outcome measures (a) Withdrawal rates (total rate; withdrawal due to adverse events; withdrawal due to treatment failure) (b) Adverse events (local and systemic) (i) Findings from the main review (ii) Findings from the separate search for additional studies of adverse events (c) Quality of life measures (d) Economic outcomes (e) Concordance or compliance with treatment Discussion
Types of studies We included randomised controlled trials in the review. Trials could be either placebo-controlled or head-to-head with a vitamin D preparation (head-to-head trials compare two active treatments with each other). The types of study design eligible for inclusion were: parallel group (between-patient), cross-over and within-patient designs. For within-patient studies, where study participants serve as their own control, we included only those studies that clearly adopted a left-right design and we excluded studies where multiple plaques are treated with more than two products. If no useful effectiveness, withdrawal or adverse events data were available, either from the published paper or from sponsors or triallists, we excluded the study. The search for longer-term adverse events included studies of any design that included humans (i.e. not only animals; either humans only or humans and animals). However, studies with fewer than ten participants (including case reports) were not eligible for inclusion. We did not restrict the search for compliance studies by study design.
Types of participants People of any age with chronic plaque psoriasis affecting the body, limbs and/or scalp. We did not limit participant type by area of involvement, disease severity or skin area treated.
7
Types of interventions Topical treatments, including: 1. vitamin D preparations, e.g. calcipotriol; 2. corticosteroids, e.g. betamethasone valerate; 3. coal tar; 4. dithranol, also known as anthralin; 5. salicylic acid, urea; 6. topical retinoids; 7. topical immunosuppressants e.g. methotrexate; 8. topical macrolactams e.g. ascomycin derivatives such as tacrolimus; 9. combination products e.g. corticosteroids with coal tar or corticosteroids with vitamin D. We compared topical treatments with vehicle (placebo). We also compared vitamin D analogues with other topical treatments. Vitamin D analogues were selected for this comparison because they are rst-line treatments in many developed countries (van de Kerkhof 1998). The potency of topical corticosteroids was based on classications from a previous review (Mason 2002b). The review included any topical treatment for psoriasis, except for products for which (a) no licence was obtained and (b) research into the product was discontinued. The reason for this exclusion criterion is that these products are unlikely to be of interest to people making decisions about health care, such as policy makers, people with psoriasis or clinicians. Although they may be of interest to researchers, lessons from the research into failed molecules are likely to have been reected in the development of subsequent products. Trials of systemic or UV treatments with adjunctive topical treatment were not eligible for inclusion in the review.
Search methods for identication of studies
Electronic searches Search strategies run in 1999 for a previous review (Mason 2002a) were re-run in 2002 (Mason (unpublished)). Therefore, the information specialists undertook searches to identify studies published since 2002 (see Acknowledgements). The information specialists updated the search strategies to reect changes in the interfaces, MESH headings and to incorporate terms for newly licensed products. Relevant trials were identied from the Cochrane Skin Groups Trials Register (searched 4th December 2004), which contains the results of a comprehensive programme of ongoing hand searching of dermatological journals and conference proceedings (see Appendix 1). In February 2005, the following databases were searched for effectiveness RCTs of psoriasis treatments: EMBASE (Ovid web interface) (see Appendix 2) MEDLINE (Ovid web interface) (see Appendix 3) Science Citation Index (ISI web of Knowledge interface) (see Appendix 4) Biosis (EDINA interface): publication years 2001 to 2005 (see Appendix 5) Dissertation Abstracts (Dialog Classic interface) (see Appendix 6) Inside Conferences (Dialog Classic interface) (see Appendix 6) SIGLE (WebSPIRS interface): publication years 2001 to 2005 (see Appendix 7) CENTRAL (Cochrane Library CD-ROM 2005 issue 1) (see Appendix 8) National Research Register (NRR) (CD-ROM interface, issue 2004/4) (see Appendix 8)
Types of outcome measures Table 2 provides an overview of the effectiveness outcome measures included in the review.
Search update: 2008
Primary outcomes
(a) Investigator assessment of overall global improvement (IAGI) (b) Total severity scores (TSS) (c) Psoriasis area and severity index (PASI) (d) Patient assessment of overall global improvement (PAGI)
Secondary outcomes
(a) Withdrawal rates (total rate; withdrawal due to adverse events; withdrawal due to treatment failure). (b) Adverse events (local and systemic). (c) Quality of life measures. (d) Economic outcomes. (e) Concordance or compliance with treatment.
Findings presented in this review relate to studies identied from the searches run in 2005. In November 2008, the search strategies were updated to identify recently published studies to be listed in the Studies awaiting classication section. The Cochrane Skin Groups Trials Register was searched on 17th November 2008 (see Appendix 1). SIGLE has not been updated since 2005, so this database was not searched in 2008. The NRR is no longer in existence and has been replaced by the UK Clinical Research Network Study Portfolio. Information specialists updated the remaining search strategies as appropriate and strategies were run on the following databases for trials of psoriasis treatments that had been added since 2005: EMBASE (OvidSP Online) (see Appendix 2) MEDLINE (OvidSP Online) (see Appendix 3) Science Citation Index (SCI; ISI web of Knowledge interface) (see Appendix 4) Biosis (Dialog Classic Online) (see Appendix 5) Dissertation Abstracts (Dialog Classic Online) (see Appendix 6)
8
Inside Conferences (Dialog Classic interface) (see Appendix 6) CENTRAL (Cochrane Library Online) (see Appendix 8) UK Clinical Research Network Study Portfolio (http://public.ukcrn.org.uk/search/) (see Appendix 8).
Using the phrase psor% AND vitamin D retrieved 25 hits Using the phrase psor% AND topical AND corticost% retrieved 55 hits Using the phrase psor% AND tar retrieved 10 hits In total, 22 potentially relevant trials were identied. Details are provided in Characteristics of ongoing studies.
Results from the effectiveness RCT searches (2005)
For each database, the numbers of records identied are shown. The total number of new records assessed after deduplication against each other and previously identied records was 1839. EMBASE: 843 MEDLINE:1048 Science Citation Index : 300 Biosis: 158 Dissertation Abstracts: 6 Inside Conferences: 10 SIGLE: 5 CENTRAL: 371 NRR: 152
Adverse effects
In February 2005, the following databases were searched over the following time periods, for studies of adverse events of specic psoriasis treatments: EMBASE (Ovid web interface) (see Appendix 9) MEDLINE (Ovid web interface) (see Appendix 10) Searches were limited to publications in the years 1990 to 2005, and published in English. In MEDLINE, the search was designed to omit records with the following Publication Types: Note, Comment and Editorial. The search strategy for MEDLINE is listed below. EMBASE was searched using a similar strategy, adapted according to the interface and syntax requirements. Relevant adverse effects studies identied during the screening for effectiveness trials were also considered.
Results from the effectiveness RCT update searches (2008)
For each database, the numbers of records identied are shown. The total number of new records assessed after deduplication against each other and previously identied records was 2714. EMBASE: 1653 MEDLINE: 1487 SCI: 2762 Biosis: 72 Dissertation Abstracts: 3 Inside Conferences: 0 CENTRAL: 127 UK Clinical research network: 20 Potentially relevant studies identied from the 2008 update searches are listed in the Studies awaiting classication section.
Results from the adverse events searches (2005) For each database, the numbers of records identied are shown. The total number of new records assessed after deduplication against each other and previously identied records was 2013. EMBASE: 1645 MEDLINE: 1022
Adverse events search update: 2008 In December 2008, the searches for studies of adverse events of specic psoriasis treatments were updated. The search strategies were based on those used in 2005 but were revised and updated to incorporate recent research into searching for adverse events. For this reason searches were extended back to 1990. EMBASE (Ovid web interface) (see Appendix 9) MEDLINE (Ovid web interface) (see Appendix 10)
Searching other resources
References from published studies and reviews
These were checked for further trials. Results from the adverse events search update (2008)
Unpublished literature
We routinely contacted triallists and companies for newly published studies and missing data. The metaRegister of Current Controlled Trials was searched for ongoing trials on http:// www.controlled-trials.com/mrct/. The register was searched in July 2008. Using the phrase psor% AND topical retrieved 106 hits Using the phrase psor% AND calcipot% retrieved 12 hits
For each database, the numbers of records identied are shown. The total number of new records assessed after deduplication against each other and previously identied records was 905. EMBASE: 1302 MEDLINE: 1482 Potentially relevant studies identied from the 2008 update searches were added to the Classication pending references section.
9
Concordance / compliance
Data extraction and management We summarised the major attributes of trials, including treatment forms, doses and duration, inclusion and exclusion criteria, level of blinding, within-patient or between-patient (parallel group) design, method of generation of the randomisation sequence, concealment of allocation, numbers of participants randomised, baseline comparability, loss to follow up, primary and secondary outcomes, withdrawals and adverse events. We extracted data from trials on the three commonly reported clinical outcomes: Investigator Assessment of Global Improvement (IAGI); Total Severity Score (TSS); Psoriasis Area Severity Index (PASI). Where available, we also extracted data on: Patient Assessment of Global Improvement (PAGI); quality of life measures; economic outcomes. If compliance with treatment was reported, we also extracted these data. In addition, we extracted data on withdrawal due to any cause, to adverse events and to treatment failure, as well as adverse events due to local and systemic effects. For each outcome measure under a comparison, we included the same treatment options regardless of data availability (see Data and analyses). We did this for three reasons. Firstly, an inclusive approach makes clear that there is an absence of data, not that data have been omitted. Secondly, if data subsequently become available when the review is updated in future, the correct structure is available for data entry. Thirdly, this approach ensures treatments are always ordered identically regardless of outcome (e.g. in all outcomes for vitamin D vs. placebo, maxacalcitol is always the sixth treatment reported).
In December 2007, the following databases were searched over the following time periods, for studies of compliance with psoriasis treatments: EMBASE (Ovid web interface): EMBASE 1980 to 2007 Week 50 (see Appendix 11) MEDLINE (Ovid web interface): database updates 1950 to December Week 2 2007 (see Appendix 12). Searches were not restricted by study design or by language of publication. Results from the compliance searches For each database, the numbers of records identied are shown. The total number of new records assessed after deduplication against each other and previously identied records was 246. EMBASE: 162 MEDLINE: 171
Language restrictions
There were no language restrictions when searching for effectiveness RCTs or compliance studies. Searches for studies of adverse events were restricted to those published in English.
Data collection and analysis
Selection of studies Titles and (where available) abstracts identied from the searches were screened by two authors (AM, JM) and another author (MC) acted as an arbiter when necessary. In our protocol, we stated our intention that studies meeting only some of the inclusion criteria stated above would be listed as excluded studies. However, it became clear that this was not feasible, as large numbers (over one thousand) of studies would need to be cited. Therefore, only those studies that were deemed potentially eligible for inclusion and for which full papers were retrieved, but which were subsequently found to fail to meet the inclusion criteria, were listed as excluded studies. For the separate search for studies exploring adverse events, studies were eligible if they addressed safety or tolerability issues, focused on drugs included in the main review, and were longer-term in follow-up (> 12 weeks). Short-term studies (with follow-up < 12 weeks) were eligible for inclusion only if they were designed specifically to consider adverse effects, tolerability or safety. Studies that included fewer than ten participants (including case reports) were not eligible for inclusion. For the separate search for studies of compliance with treatment, studies were eligible if they addressed compliance with topical treatment in people with any type of psoriasis.
Assessment of risk of bias in included studies
Assessment of methodological quality
The quality assessment included an evaluation of each included study, based on the following components that are considered to be associated with biased estimates of treatment effect (Juni 2001): (a) the method of generation of the randomisation sequence; (b) the method of allocation concealment - it was considered adequate if the assignment could not be foreseen; (c) who was blinded / not blinded (participants, clinicians, outcome assessors); (d) how many participants were lost to follow up. In addition the quality assessment included: (e) baseline assessment of the participants for age, sex, duration and severity of psoriasis; (f ) baseline comparability of intervention and control groups.
10
We recorded the information in the section Characteristics of included studies. Measures of treatment effect
Summarising primary outcomes with standardised mean differences
We extracted data on four primary outcome measures: the IAGI (Investigator assessment of overall global improvement); the TSS (total severity score); the PASI (Psoriasis Area and Severity Index); the PAGI (Patient assessment of overall global improvement).
We pooled results from trials using any of these outcome measures using a standardised mean difference (SMD) metric. Table 2 summarises the characteristics of the outcome measures. Trials often reported more than one measure. Figure 3 and Figure 4 show how using a combined endpoint allows more data to contribute to an overall analysis and so facilitate treatment comparisons. We constructed the combined endpoint by taking IAGI data when available, and failing this, TSS, PASI or PAGI data in that order of availability. For PASI and TSS, some included trials reported change scores and others reported endpoint scores. In view of the mix of endpoint/ change scores and of the variation in scale, we analysed ndings using a standardised mean difference statistic in a random-effects model.
11
Figure 3. Placebo comparisons: data reported by outcome
12
Figure 4. Head-to-head comparisons: data reported by outcome
SMDs were also expressed in physical units adjusting by the appropriate pooled standard deviation estimate (Table 3).
Secondary outcomes
metric. This is more appropriate than a xed effect model since denitions of withdrawal and adverse events vary between trials.
We summarised data on adverse events, quality of life measures, economic outcomes and concordance as narratives. Withdrawal data were summarised using a random effects risk difference (RD)
Unit of analysis issues Within-patient studies are statistically analogous to cross-over studies and results should be adjusted by the correlation coef13
cient (Cochrane Handbook, section 16.4.6)(Higgins 2008). No study included in the review reported this statistic and we did not have access to patient-level data, so could not estimate it directly. Although the statistic can be imputed, this is not recommended for SMD estimates (which are used in this review) (s. 16.4.6.2). On the subject of cross-over studies, the Cochrane Handbook states (s. 16.4.5)(Higgins 2008): A common situation is that means and standard deviations (or standard errors) are available only for measurements on E [experimental group] and C [control group] separately. A simple approach to incorporating cross-over trials in a meta-analysis is thus to take all measurements from intervention E periods and all measurements from intervention C periods and analyse these as if the trial were a parallel group trial of E versus C. This approach gives rise to a unit-of-analysis error (see Chapter 9, Section 9.3) and should be avoided unless it can be demonstrated that the results approximate those from a paired analysis, as described in Section 16.4.4. The reason for this is that condence intervals are likely to be too wide, and the trial will receive too little weight, with the possible consequence of disguising clinically important heterogeneity. Nevertheless, this incorrect analysis is conservative, in that studies are under-weighted rather than over-weighted. While some argue against the inclusion of cross-over trials in this way, the unit-of-analysis error might be regarded as less serious than some other types of unit-of-analysis error. Consequently we have included within-patient studies as though they were parallel-group studies, accepting that they are underweighted. To explore whether it was appropriate to combine these trials, we used sensitivity analysis to see how effect size varied for within and between-patient studies. If magnitude of effect varied consistently between the two study designs, this would strongly suggest a nonzero correlation coefcient and it would be appropriate to separate the trials. The analysis found no evidence that the magnitude of effect varied consistently: within-patient trials did not consistently demonstrate smaller or larger effects than between-patient trials. In the interests of statistical purity, these trials could (a) be reported separately or (b) be removed altogether. The drawback of option (a) is that it makes an already complex review even more complex and less accessible; the disadvantage of (b) is that it removes data that might be of interest to clinicians and people with psoriasis. On balance, we prefer to report relevant randomised data wherever possible to help inform pragmatic decision making.
of treatment cohorts fully reported in trials and adjusted for scale size. We made separate imputations for each outcome measure (see Table 3): for within-patient and between-patient (parallel group) designs; for endpoint and change scores; for scalp trials. Within-patient designs are statistically analogous to crossover studies and the precision of their ndings within a meta-analysis needs adjustment for within-patient correlation. We attempted to explore this by sensitivity analysis.
Subgroup analysis and investigation of heterogeneity We examined ndings by agent class (as our primary analysis) and individual topical agent (within class analysis). When comparing trials both within and across therapeutic classes, the summary estimates may demonstrate substantial heterogeneity. It would be appropriate to try to nd reasons for individual differences, but there are too many possible explanations and too few trials to do this: reasons might include differences in trial design, length of follow-up, participant selection, adequacy of concealment of allocation, adequacy of blinding, and source of funding. The Cochrane Handbook explicitly endorses the combination of apples and oranges if they are used to contribute to a wider question about fruit. (s. 9.5.1)(Higgins 2008). Our purpose is to identify whether classes of topical treatments work and are safe. To this end, there is a fundamental difference between heterogeneity that makes it uncertain whether individual people with psoriasis will derive any benet from a treatment and heterogeneity that makes the size of positive benet imprecise. Clinicians and those with psoriasis will still value information about a treatment that is benecial even though its magnitude is poorly understood. However we clearly state the presence of heterogeneity where it occurs.
Sensitivity analysis We used a meta-analysis with a random effects estimation both for measures of effect and for pooling of risk differences for adverse events. We tested for heterogeneity using the I statistic. If we identied outliers, we undertook a sensitivity analysis to investigate the implications of their exclusion. In addition, we undertook sensitivity analyses to investigate the impact of within-patient vs. between-patient trials and to explore the effects of treatments for scalp psoriasis. In some comparisons, there were no, or relatively few, studies that included both within-patient and between-patient designs and/or few participants contributing data. We used the following criteria to decide whether an analysis should be included in the sensitivity analysis: Numbers of participants contributing data
14
Dealing with missing data We routinely contacted triallists and companies for newly published studies and missing data. Where studies did not report estimates of variance, we derived them from condence intervals (CIs) or from P values where possible. Where we could not obtain estimates of variance, we imputed them deterministically by pooling the standard deviations
Numbers of studies included in the comparison Frequently-used products in clinical practice Includes both within-patient and between-patient designs (for within/between-patient sensitivity analysis) Includes scalp trials (for scalp trial sensitivity analysis) Based on these criteria, we selected ve comparisons (analyses 1; 2; 3 ; 7; and 13) for sensitivity analysis. To ensure sufcient data were available, we analysed the combined endpoints. These analyses cover vitamin D analogues and corticosteroids, which are amongst the most frequently-used products in clinical practice. Of the 18 scalp trials included in the review, 16 contributed effectiveness data (Table 4). Analysis 13 did not include any trial of scalp psoriasis. In total, nine scalp trials contributed to the sensitivity analysis, with the number of trials within each comparison ranging from one to ve.
In 96 trials, some or all outcome data were missing. We contacted triallists or sponsors to request missing data, and received data for 33 of these trials. We excluded trials that reported no useable outcome data. We did not contact triallists or sponsors for missing adverse events or withdrawal data.
Included studies The review included 131 studies (see Characteristics of included studies): 82 of these were placebo-controlled, 57 compared treatments head-to-head with 8 trials reporting both placebo-controlled and head-to-head comparisons. The eight trials reporting both head-to-head and placebo comparisons contributed only once to the analysis of study characteristics, unless the trial involved entirely distinct participants in its placebo-controlled and activecontrolled analyses. For example, the trial by Guenther 2002 compared treatments against each other (Guenther 2002 (H)) and against placebo (Guenther 2002 (P)). This study contributed only once to the analysis of study characteristics (number of participants; proportion of males etc). However, two trials reported placebo and head-to-head analyses involving entirely separate participants (Barker 1999 (P) and Barker 1999 (H); Grattan 1997 (P) and Grattan 1997 (H)). Therefore the total number of studies contributing data to the analysis of study characteristics and quality assessment was 133 (= 82+57-8+2). There were 3 trials of nail psoriasis (Cannavo 2003; Scher 2001; Tosti 1998), 18 trials of scalp psoriasis (Duweb 2000; Elie 1983; Ellis 1988; Franz 1999; Franz 2000;Green 1994; Jarratt 2004; Kanzler 1993; Kiss 1996; Klaber 1994; Klaber 2000b; Kse 1997; Lepaw 1978; Olsen 1991; Pauporte 2004; Reygagne 2002b; Shuttleworth 1998; van de Kerkhof 2002a), and 3 trials of inverse psoriasis (Gribetz 2004; Lebwohl 2004; Ortonne 2003). One trial evaluated psoriasis in children (Oranje 1997). Most trials were conducted in ambulatory care settings, but four trials were of hospitalised participants (Grattan 1997 (H); Grattan 1997 (P); Kragballe 1991a; Monastirli 2000; van der Vleuten 1995). Eighty-ve trials adopted a between-patient (parallel-group) design and 47 were within-patient trials and 1 trial used both designs (Henneicke-v. Z. 1993). The 133 studies included 21,448 participants. Of these studies, 99 provided data on the age of participants. The mean age of all participants for which studies provided data was 46.4 years (range: 2 to 97 years) (N = 18,263). Data on the gender of participants (N = 18,279) were available from 105 studies. Overall, participants were more likely to be male: the mean proportion of males was 58.8% (range: 30% to 100%). Fifteen studies did not report the overall baseline severity of study participants (e.g. participants with mild to moderate disease) and in 56 studies baseline severity was unclear. Fifty-two studies re15
Other
A consumer was involved throughout the review process to help ensure the readability of the nal review.
RESULTS Description of studies

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classication; Characteristics of ongoing studies.
Results of the search We previously conducted a systematic review of this topic area in 2002 and identied 4359 records and 118 studies studies: 67 trials reported only placebo-controlled comparisons, 43 trials reported only head-to-head comparisons and 8 trials reported both placebocontrolled and head-to-head comparisons (Mason (unpublished)). For the Cochrane review, we excluded two of these placebo studies because no relevant effectiveness or withdrawal data were available (Jansen 1986; Lebwohl 2001) and excluded a further placebo-controlled study because the randomisation process was considered to be unsound (Kragballe 1989). The effectiveness RCT search strategies undertaken in 2005 identied 1839 new records. Of these, we retrieved 88 papers and screened these for eligibility (some papers were multiple reports of the same trial). We included 16 new studies in the review: 10 placebo-controlled trials and 6 head-to-head trials. Of the ten placebo-controlled trials, eight provided effectiveness data and ten provided data on withdrawals (therefore, eight trials provided both types of data). All six head-to-head trials provided both effectiveness and withdrawal data.
ported baseline severity. In a further ten studies, studies reported sufcient information on global severity scores, such as the mean and variation in baseline PASI or the percentage of body surface area (BSA) affected, to allow us to infer global severity using guidance on the interpretation of severity scores (Finlay 2005; Krueger 2000). In the 62 trials where severity was assessable, participant severity was classied as mild (3 studies, 5%), mild to moderate (20 studies, 32%), mild to severe (5 studies, 8%), moderate (10 studies, 16%), moderate to severe (14 studies, 23%) and severe (10 studies, 16%). However, 71 studies (53%) either provided insufcient information to allow an assessment of clinical severity to be made or indicated that a wide range of severity was included. Therefore, we could not make assessments of the clinical characteristics of participants in studies reporting only the mean PASI (with no information about variation) or reporting only localised (e.g. TSS) scores. One example of a study that included subjects with a wide range of severity scores is the trial by Cunliffe 1992 where the mean baseline PASI was 9.0 (suggesting moderately severe disease, according to Finlay 2005), but where individual participant scores ranged from 0.6 to 41.2. Another example is the study by Olsen 1996 (1), where participant BSA involvement averaged 12%, but ranged from 1 to 80%. It is unclear how participant severity was distributed within these ranges (i.e. whether these extremes were outliers or whether a sizeable proportion of participants was clustered at the extreme ends of the distribution). Even where triallists classied participant severity, it was not always clear that this was consistent with published guidance, which itself does not always provide consistent messages. For example, Finlay 2005 states that a PASI score > 10, or a BSA involvement > 10%, or Dermatology Life Quality Index (DLQI) > 10, constitutes severe disease. However, Krueger 2000 argues that BSA is unreliable as an indicator of severity, which is better proxied by quality of life assessments. Quality of life was, however, rarely assessed in the included studies. Given this lack of clarity and the absence of adequate severity data in over half (53%) of the included studies, we could not explore baseline participant severity in sensitivity analyses, nor reliably use it to investigate inter-study heterogeneity. All 133 studies provided data on treatment duration (mean: 6 weeks, range: 1 to 24) and follow-up duration (mean: 9 weeks, range: 2 to 52), where follow-up duration is dened as including the treatment period. Commonly-used outcomes assessed by the studies included; individual signs (erythema, scaling, induration) (82 of the 133 studies); Total Severity Score or Total Sign Score (52 studies); PASI (46 studies); IAGI (71 studies); PAGI (28 studies). Outcome measures employed by small numbers (< 5) of trials included; Local Psoriasis Severity Index (scale not reported);
Patient Self-Assessment (4-point scale assessing control of psoriasis over previous week); Jacoby assessment score (0 to 7 score transformed to % clinical improvement); investigator assessment of skin staining. Trials seldom assessed quality of life (four trials). Participant-reported outcomes included: overall patient assessment (relative efcacy, speed of response, irritation, staining, ease of application); patient global assessment of acceptability of treatment; patient assessment of likely compliance; patient assessment of cosmetic acceptability. The 18 scalp trials and 3 trials of inverse psoriasis used standard measures, but the 3 trials of nail psoriasis reported specialised outcome measures such as assessments of onycholysis, hyperkeratosis, pitting, crumbling, oil drop (each scored on a 4 point scale) and nail thickness. Trials of placebo-controlled trials were grouped by type of treatment (e.g. vitamin D products), and head-to-head trials were grouped in a similar way (e.g. vitamin D vs. potent corticosteroid). Eighteen comparisons were included in the review. Since many trials did not specify the severity of participants psoriasis, it was not possible to use severity to inform pooling decisions. The primary analysis explored the results of pooling within these 18 comparison groups using a random effects model. In addition, sensitivity analysis was undertaken for a limited number of comparisons using the combined endpoint. These analyses used pooled data to explore within- and between-patient trial variation and to explore variation in scalp vs. body psoriasis. In 116 of the 133 studies included in the review, all participants applied their own treatments. Nurses applied treatments in 1 trial (Geilen 2000), participants parents delivered some care in the trial of childhood psoriasis (Oranje 1997) and the delivery method was unclear in 16 studies.
Excluded studies We excluded 22 studies from the updated review (see Characteristics of excluded studies). The most common reason for exclusion was that the study did not provide adequate data and requests for missing data from triallists or sponsors were unsuccessful (N = 9). Seven studies were excluded because the comparator was not strictly placebo. In two studies, the randomisation method was clearly inadequate, two studies used concomitant UV light, one study was untranslatable and one evaluated an unlicensed product that was not subsequently marketed.
Risk of bias in included studies

16
We extracted and tabulated data on six quality indicators. Summary ndings are presented narratively, with characteristics for all studies presented in the Characteristics of included studies tables. All included trials were randomised, but only 32 /133 clearly reported the method used to randomise participants. Concealment of treatment allocation was explicitly adequate in 12 trials, but 105 trials blinded participants to treatment allocation. One-hundred and twenty-one studies reported loss to follow up data and 84 trials demonstrated that groups were comparable at baseline. Allocation Of the 133 studies assessed for quality, adequate concealment of treatment allocation was explicitly achieved in 12 (9.0%). Concealment was unclear in the majority of studies (119 studies; 89.5%) and inadequate in two studies (1.5%). Blinding Most (105/133) studies were double-blind, with 8 studies adopting a single-blind (investigator only) approach. Twelve studies were open (no blinding) and in the remaining 8 studies the blinding approach adopted was unclear. Nineteen trials explicitly stated that the outcome assessor was blinded to treatment allocation. However, the outcome assessor will also have been blinded in doubleblind trials where the investigator also acted as the outcome assessor. Incomplete outcome data Loss to follow up was dened as the number of enrolled participants who failed to contribute data for the analysis. Of the 133 studies assessed for quality, 12 (9%) provided no data on loss to follow up. For the remaining 121 studies, the mean percentage loss to follow up was 6.5% (range: 0 to 31.5%). Thirtyve studies reported that there was no loss to follow up. Two studies lost more than 25% of their participants to follow up (Henneicke-v. Z. 1993; Weinstein 2003). Where studies did not report estimates of variance, we derived them from condence intervals (CIs) or from P values where possible. Where we could not obtain estimates of variance, we imputed them (see Table 3). In total, we imputed estimates of variance in 38 studies (7 of which were scalp trials); the Characteristics of included studies table details these studies. Other potential sources of bias
randomisation design and 19 studies used computerised methods (5 studies used both). Four reported that sequential allocation had been used (three of these studies were published in the 1970s), one study stated that the investigator had undertaken the randomisation process and another study used a sealed envelope method. It could be argued that trials with sequential allocation should be excluded from the review, but this would discriminate against studies with better reporting methods in favour of those not stating the randomisation method.
Baseline assessment of the participants for age, gender and clinical characteristics
We coded studies as: y (baseline assessments for age, gender and clinical characteristics); p (at least one type of assessment); and NR (not reported or unclear). Most studies (82/133; 61.7%) provided baseline assessments of age, gender and clinical characteristics. Forty-two studies (31.6%) provided data on 1 or 2 types of assessment and 9 studies (6.8%) reported no relevant data.
Baseline comparability of intervention and control groups
We coded studies as: y (comparability demonstrated); p (comparability partially demonstrated); and NR (comparability not demonstrated or unclear). Studies could demonstrate comparability by reporting data for each group and/or by reporting the outcome of statistical tests (e.g. p values). Eighty-three studies (62.4%) demonstrated that the groups were comparable at baseline, 23 studies (17.3%) demonstrated partial comparability and 27 studies (20.3%) did not clearly demonstrate comparability between the groups.
Effects of interventions
Primary outcome measures The review analyses 18 comparisons. Of the 18 analyses, 6 are topical treatment versus placebo analyses and 12 are head-to-head analyses of a topical treatment against a vitamin D analogue (i.e. one commonly used class of treatments). Some analyses are a catch all category; for example, analysis 6 includes Other treatment vs. placebo which covers 22 treatments for which there is less research evidence (both in terms of numbers of studies and numbers of participants contributing data); similarly, analysis 18 incorporates 7 head-to-head comparisons of vitamin D analogues that are not easily classied under the other head-to-head comparisons. An overview of these analyses is given in Table 5. Figure 3 and Figure 4 provide denitions of the analyses and give an overview of the evidence base for different outcomes. Table 2 gives details of the outcome measures considered. The number of participants and number of studies are adjusted manually for within-patient
17
Method of generation of the randomisation sequence
Only randomised controlled trials were eligible for inclusion in the review. However, 101 studies (76%) did not clearly report the randomisation method used. Thirteen studies adopted a block
studies; for studies contributing more than once to a single analysis; and for studies contributing to multiple analyses. Therefore, numbers of participants and studies may differ from the gures estimated by RevMan. For each of the 18 analyses, data on 5 effectiveness outcome measures are analysed where available (1 of these 5 measures is a combined endpoint). Figure 3 demonstrates the availability of data for the six placebo analyses, with dark-coloured cells indicating that no data were available for the treatment subgroup and outcome measure. Figure 4 shows the same information for head-to head analyses. Four primary outcome measures were considered: 1. IAGI (Investigator assessment of overall global improvement); 2. TSS (total severity score) 3. PASI (Psoriasis Area and Severity Index); 4. PAGI (Patient assessment of overall global improvement). Trials often reported more than one measure. We constructed the combined endpoint by taking IAGI data when available, and failing this, TSS, PASI or PAGI data in that order of availability. For PASI and TSS, some included trials reported change scores and others reported endpoint scores. Table 2 details the characteristics of the outcome measures. In view of the mix of endpoint/ change scores and of the variation in scale, we analysed ndings using a standardised mean difference statistic in a random-effects model. There are three main sources of complexity in summarising study ndings: 1. study design (within- vs. between-patient); 2. absence of a simple one-to-one correspondence between papers, trials and comparisons (e.g. trials reporting multiple comparisons / single papers reporting multiple trials); 3. body area targeted by treatment (e.g. treatments for chronic plaque psoriasis conned to the scalp, or to nails, or exural areas (inverse psoriasis)). These three factors are discussed below. Other sources of heterogeneity include variation in trial duration, disease severity, participant demographics, treatment application method, dosing frequency, drug potency and vehicle. 1. Trials were either between-patient or within-patient designs. The former randomise participants into separate (parallel) groups; the latter randomise treatments to the left or right side of the same participant. Within- and between-patient trials have different variance structures. Furthermore, in within-patient studies the two responses (left and right) may be correlated; if there is perfect correlation, then the trial is uninformative. If there is zero correlation, then the sides of the participant are independent as in a between-patient study. We do not know the intra-group correlation and have assumed this to be zero. In a select number of comparisons, sensitivity analysis was undertaken to investigate whether effect varied by this aspect of trial design (the sensitivity analysis provided good empirical evidence for the assumption that the correlation is approximately zero).
2. There were instances of single papers reporting either multiple trials or multiple analyses within a single trial. Therefore, simple counts of numbers of participants and numbers of studies contributing data to the analysis are misleading and adjustments were made accordingly (Table 5). These numbers may not correspond exactly with the numbers estimated in RevMan, which does not account for these factors. 3. Whereas the majority of trials considered chronic plaque psoriasis on the body, some trials focused on scalp psoriasis; some reported ndings for both scalp and body psoriasis; one study reported effectiveness data on nail psoriasis; and three were of inverse (exural) psoriasis. One trial of body and scalp psoriasis reported overall outcomes (IAGI/PAGI); a scalp-only outcome (TSS); and a body-only outcome (modied PASI) (van de Kerkhof 2002a). In a select number of comparisons, sensitivity analysis was used to investigate whether effect varied in the scalp trials.
(a) Investigator assessment of overall global improvement (IAGI)
Analysis 1: vitamin D analogues vs. placebo This comparison included seven vitamin D analogues (see Analysis 1.1 and Table 6). Fifteen trials with 2556 participants reported IAGI data. Eight trials were between-patient design and seven were within-patient studies. One trial of scalp psoriasis was included (Green 1994), but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from 4 weeks to 12 weeks. The SMD across all 7 treatments for IAGI was -1.30 (95% condence intervals (CI): -1.57 to -1.03; I: 90.4%), but there was considerable variation between treatments with the effect size ranging from -1.04 (calcipotriol once-daily or twice-daily (OD/BD)) to -1.90 (Dovobet BD). There was considerable between-study variation in the IAGI SMD for calcitriol. The pooled effect was -1.25 (95% CI: -2.63 to 0.12; I: 96.1%) but this ranged from -0.26 (95% CI: -0.99 to 0.47) for Langner 2001 (P) to -3.11 (95% CI: -3.57 to -2.66) for Perez 1996. The magnitude of the IAGI SMD for the Perez study is the highest across all comparisons, outcomes and treatments. For the combined endpoint of this analysis, the impact of removing this trial from the pooled ndings was explored using sensitivity analysis. The presence of substantial heterogeneity means that the estimated average benet should be treated with caution. Analysis 2: Corticosteroid (potent) vs. placebo This comparison included 11 potent corticosteroids (see Analysis 2.1 and Table 7). Eleven studies with 1232 participants reported IAGI data on 6 of these 11 treatments. Ten trials were betweenpatient design and one was a within-patient study. Two trials of scalp psoriasis were included but no trial of nail or inverse psoriasis
18
was identied. Treatment duration ranged from 3 to 12 weeks. The SMD across all six treatments for IAGI was -1.09 (95% CI: 1.26 to -0.92; I: 34.9%). All six treatments performed statistically signicantly better than placebo. Analysis 3: Corticosteroid (very potent) vs. placebo This comparison included four very potent corticosteroids (see Analysis 3.1 and Table 8). Five studies with 684 participants reported IAGI data. There were four between-patient trials and one within-patient study. Three trials of scalp psoriasis were included but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from two to three weeks. The IAGI SMD across all four treatments was -1.42 (95% CI: -1.72 to -1.11; I: 59.6%). All four treatments performed statistically signicantly better than placebo. Analysis 4: Dithranol vs. placebo This comparison considered dithranol against placebo (see Analysis 4.1 and Table 9). One within-patient trial reported IAGI data for eight participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was three weeks. The SMD for the IAGI was -1.14 (95% CI: -2.22 to -0.06; I: NA). Analysis 5: Tazarotene vs. placebo Our review did not identify any study comparing tazarotene against placebo and that reported IAGI data. Analysis 6: Other treatment vs. placebo This comparison comprised all other treatments not included in the rst ve analyses; therefore, pooling was removed. None of the studies assessed the same treatment. In total, 22 treatments are included in this analysis (see Analysis 6.1 and Table 10). Nine studies with 401 participants reported IAGI data on 10 of these 22 treatments. Five trials were between-patient design and four were within-patient studies. Two trials of scalp psoriasis and one trial of inverse psoriasis were included, but no trial of nail psoriasis was identied. Treatment duration ranged from 3 to 12 weeks. Six treatments performed statistically signicantly better than placebo: anti IL-8 monoclonal antibody cream; betamethasone17,21-dipropionate plus salicylic acid; betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid; methotrexate gel; pimecrolimus cream; and salicylic acid. The effect size for the IAGI ranged from -0.56 (Sutton 2001; methotrexate gel) to -1.68 (Elie 1983; betamethasone-17,21-dipropionate plus salicylic acid). In four treatments, the difference relative to placebo was not statistically signicant: hexauoro-1,25-dihydroxyvitamin D3; oleum horwathiensis; platelet aggregation activating factor (PAF); and coal tar. We did not nd any treatment that was statistically signicantly less effective than placebo.
Analysis 7: vitamin D analogues vs. corticosteroid (potent) This comparison included eight vitamin D analogue-potent corticosteroid contrasts (see Table 11). Eight studies with 2057 participants reported IAGI data for 6 of the 8 intervention-comparator contrasts (see Analysis 7.1). Seven trials were between-patient design and one was a within-patient study . Two trials of scalp psoriasis were included but we identied no trial of nail or inverse psoriasis. Treatment duration ranged from 3 to 8 weeks. The SMD across all 6 treatments for IAGI was 0.07 (95% CI: -0.11 to 0.26; I: 73.9%). One of the six vitamin D analogues performed statistically signicantly better than the potent corticosteroid. This nding came from a single between-patient study in which 99 participants contributed data (Bruce 1994). The SMD for calcipotriol against uocinonide 0.05% ointment was -0.58 (95% CI: -0.99 to -0.18; I: NA). Calcipotriol was statistically signicantly less effective than diorasone diacetate 0.05% ointment in a within-patient trial of 128 participants, SMD: 0.27 (95% CI: 0.02 to 0.52; I: NA)(Medansky 1996). We found no statistically signicant difference for any of the remaining four interventioncomparator contrasts.
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) Our review did not identify any study comparing vitamin D analogues against very potent corticosteroids and that reported IAGI data.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid This comparison considered vitamin D analogues-potent steroid combination against potent corticosteroid (see Analysis 9.1 and Table 12). One between-patient trial reported IAGI data for 732 participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was four weeks. The trial compared Dovobet BD with betamethasone dipropionate (BMD) 0.5mg/g in the same vehicle used for the vitamin D-steroid preparation. The SMD for the IAGI was -0.46 (95% CI: -0.60 to -0.31; I: NA).
Analysis 10: vitamin D analogues vs. dithranol This comparison considered vitamin D analogues against dithranol (Analysis 10.1 and Table 13). Three intervention-comparator contrasts were identied: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. Four between-patient trials reported IAGI data for 1022 participants on two of these three intervention-comparator contrasts. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration ranged from 8 weeks to 12 weeks. There was some variation in the dithranol regimens employed by trials and in the baseline severity of trial participants.
19
These factors may explain the high level of heterogeneity found in some of the pooled results. The SMD for the IAGI was -0.40 (95% CI: -0.87 to 0.07; I: 92.1%). The presence of substantial heterogeneity means that the estimated average benet should be treated with caution. Data from three trials contributed to the SMD for the calcipotriol vs. dithranol: -0.69 (95% CI: -0.86 to -0.51; I: 36.6%), indicating that calcipotriol was statistically signicantly more effective than dithranol. Data from one trial contributed to the SMD for the calcitriol vs. dithranol: 0.51 (95% CI: 0.13 to 0.88; I: NA), indicating that dithranol was statistically signicantly more effective than calcitriol.
of these 11 intervention-comparator contrasts. Six trials were between-patient and one was within-patient in design. Treatment duration ranged from four to eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, vitamin D plus corticosteroid appeared to be more effective than vitamin D alone: the SMD for the IAGI was 0.46 (95% CI: 0.27 to 0.66; I: 86.3%). This nding applied to all but one of interventioncomparator contrasts: when calcipotriol was compared with a regimen of calcipotriol (morning) plus clobetasone butyrate (nighttime), we found no statistically signicant difference (SMD: 0.00; 95% CI: -0.21 to 0.21)(Kragballe 1998b).
Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid Analysis 11: vitamin D analogues vs. coal tar We found evidence for one vitamin D analogue (calcipotriol) for this comparison (see Analysis 11.1 and Table 14). Calcipotriol was compared with coal tar alone and with coal tar plus white soft parafn. Two trials, one between-patient and one within-patient, with 57 participants reported IAGI data. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Treatment duration was 6 weeks. The SMD for the IAGI was -1.13 (95% CI: -1.60 to -0.67; I: 0%), with similar effect sizes for the comparison against coal tar alone (SMD: -1.01; 95% CI: -1.77 to -0.24) and against coal tar plus white soft parafn (SMD: -1.21; 95% CI: 1.79 to -0.62). This comparison involved calcipotriol against betamethasone dipropionate with salicylic acid (see Analysis 14.1 and Table 17). One between-patient trial with 200 participants contributed IAGI data. Treatment duration was six weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. We found no statistically signicant difference between the 2 regimens: the SMD for the IAGI was -0.06 (95% CI: -0.33 to 0.22; I: NA).
Analysis 15: Calcipotriol vs. coal tar polytherapy This comparison involved calcipotriol against coal tar polytherapy (see Analysis 15.1 and Table 18). Three intervention-comparator contrasts were included: calcipotriol vs. coal tar, coconut oil and salicylic acid (for psoriasis of the scalp); calcipotriol vs. coal tar, allantoin and hydrocortisone cream; and calcipotriol vs. dithranol and tar. Three between-patient trials with 626 participants contributed IAGI data for all three intervention-comparator contrasts. Treatment duration ranged from four to eight weeks. Two trials of scalp psoriasis were included, one of which also treated and assessed the body using high dose calcipotriol ointment, 50 mcg/ g (80-100 g/wk) and calcipotriol scalp solution, 50 mg/ml (3050 ml/wk (van de Kerkhof 2002a). However, no nail psoriasis or inverse psoriasis was identied. Overall, we found calcipotriol to be statistically signicantly more effective than coal tar polytherapy: the SMD for the IAGI was -0.52 (95% CI: -0.68 to -0.36; I: 0%). Calcipotriol was statistically signicantly more effective than its comparator in each of the three intervention-comparator contrasts.
Analysis 12: vitamin D analogue vs. vitamin D analogue Our review identied three intervention-comparator contrasts in this comparison: calcipotriol vs. calcitriol; calcipotriol vs. tacalcitol; and calcipotriol vs. maxacalcitol (see Analysis 12.1 and Table 15). Two trials involving 252 participants contributed IAGI data for 2 of these intervention-comparator contrasts. One trial was between-patient and one within-patient in design. Treatment duration was eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied and no IAGI data on calcipotriol vs. calcitriol were available. The SMD for the IAGI was -0.06 (95% CI: -0.93 to 0.82; I: 87.9%). The presence of substantial heterogeneity reects differences in the ndings from the two intervention-comparator contrasts underlying this statistic. A statistically signicant difference in favour of calcipotriol was in the analysis against tacalcitol (SMD: -0.47; 95% CI: -0.73 to -0.21) but the difference relative to maxacalcitol was not signicant (SMD: 0.43; 95% CI: -0.12 to 0.98).
Analysis 16: Head-to-head calcipotriol: Dosing This comparison explored different dosing regimens for calcipotriol (see Analysis 16.1 and Table 19). Two intervention-comparator contrasts were included: calcipotriol BD vs. calcipotriol OD, and calcipotriol BD vs. calcipotriol in the morning (OM) and placebo at night (ON). One between-patient trial with 344 participants contributed IAGI data for the comparison involving calcipotriol OM, placebo ON. Treatment duration was eight
20
Analysis 13: Vitamin D vs. vitamin D and corticosteroid Our review identied 11 intervention-comparator contrasts, involving two vitamin D analogues, one combination product and six different corticosteroids (see Analysis 13.1 and Table 16). Seven trials involving 2831 participants contributed IAGI data for 7
weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. We found that calcipotriol BD was statistically signicant more effective than calcipotriol OD (plus placebo): the SMD for the IAGI was -0.27 (95% CI: -0.48 to -0.06; I: NA).
Analysis 2: Corticosteroid (potent) vs. placebo Our review included 11 potent corticosteroids in this comparison (see Analysis 2.2 and Table 7). Eleven studies reported TSS data contributed by 1536 participants on nine of these 11 treatments. Ten trials were between-patient studies and there was one withinpatient design. Three trials of scalp psoriasis were included but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from 2 to 12 weeks. The average effect size across all 9 treatments for TSS was -0.84 (95% CI: -1.01 to -0.67; I: 42.7%). All treatments were found to be statistically signicantly superior to placebo except for diorasone diacetate: SMD: -0.34 (95% CI: -0.75 to 0.07).
Analysis 17: Head-to-head: Occlusion This comparison explored the effect of adding occlusion to vitamin D analogues (see Table 20 ). Our review did not identify any relevant study that reported IAGI data.
Analysis 18: vitamin D analogues vs. other treatment This comparison incorporated all other vitamin D head-to-head comparisons that had not already been included (see Analysis 18.1 and Table 21). Seven intervention-comparator contrasts were included in analysis 18, with IAGI data available for one of these contrasts (calcipotriol vs. vitamin B12 cream). One within-patient trial with 13 participants contributed IAGI data (Stuecker 2001). Treatment duration was 12 weeks. We identied no trial of scalp psoriasis, nail psoriasis or inverse psoriasis. We found no statistically signicant difference between calcipotriol BD and vitamin B12 cream BD: the SMD for the IAGI was -0.55 (95% CI: -1.33 to 0.24; I: NA). Analysis 3: Corticosteroid (very potent) vs. placebo Of the four very potent corticosteroids included in this comparison, two were assessed using the TSS (see Analysis 3.2 and Table 8). Six studies, all of which were between-patient trials reported TSS data for 1188 participants. Four trials of scalp psoriasis were included but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from two to four weeks. The SMD across both treatments for TSS was -1.24 (95% CI: -1.38 to 1.11; I: 9.7%). Both treatments performed statistically signicantly better than placebo.
(b) Total severity scores (TSS)
Analysis 4: Dithranol vs. placebo This comparison considered dithranol against placebo (see Analysis 4.2 and Table 9). Three within-patient trials reported TSS data for 47 participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration ranged from three to eight weeks. The SMD for the TSS was -1.06 (95% CI: -1.66 to -0.46; I: 37.4%).
Analysis 1: vitamin D analogues vs. placebo Our review included seven vitamin D analogues in this comparison (see Analysis 1.2 and Table 6). Sixteen studies reported TSS data with 2413 participants contributing data for 6 of these 7 treatments. Seven trials were between-patient design and nine were within-patient studies. One trial of scalp psoriasis was included (Green 1994), but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from 4 weeks to 12 weeks. The average effect size across all 6 treatments for TSS was -1.28 (95% CI: -1.60 to -0.95; I: 92.3%). The high level of heterogeneity means that the estimated average benet should be treated with caution: there was considerable variation between treatments with the TSS ranging from -0.66 (Tacalcitol OD) to -2.15 (Paricalcitol OD). Two studies contributed data for the SMD for the TSS of calcitriol (-2.06; 95% CI: -5.94 to 1.82), but there was a high level of heterogeneity (I2 : 98.3%). One of the studies (van de Kerkhof 1989) found no statistically signicant difference between calcitriol and placebo (SMD: -0.07; 95% CI: -0.94 to 0.81), whereas the study by Perez 1996 found a large and statistically signicant difference (-4.03; 95% CI: -4.56 to -3.50). This nding is considered in more detail in the combined endpoint section below.
Analysis 5: Tazarotene vs. placebo This comparison considered tazarotene against placebo (see Analysis 5.2 and Table 22). One between-patient trial reported TSS data for 318 participants (Weinstein 1996). No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was 12 weeks. The SMD for the TSS was -0.91 (95% CI: -1.16 to -0.67; I: NA), indicating a statistically signicant difference in favour of tazarotene.
Analysis 6: Other treatment vs. placebo This comparison comprised all other treatments that were not included in the rst ve comparisons. In total, 22 treatments are included in this analysis (see Analysis 6.2 and Table 10). Sixteen studies with 503 participants reported TSS data on 17 of these 22 treatments. Seven trials were between-patient design and nine were within-patient studies. Three trials of scalp psoriasis, one trial
21
of nail psoriasis and one trial of inverse psoriasis were included. Treatment duration ranged from 3 to 12 weeks. Ten treatments performed statistically signicantly better than placebo: anti IL-8 monoclonal antibody cream; betamethasone17,21-dipropionate plus salicylic acid; ciclosporin solution in oil (for psoriasis of the nails); sh oil plus occlusion; hexauoro-1,25dihydroxyvitamin D3; methotrexate gel; mycophenolic acid ointment; oleum horwathiensis; pimecrolimus cream; and PTH (134) in Novasome cream. The effect size for the TSS ranged from 0.48 (Sutton 2001; methotrexate gel) to -2.31 (Holick 2003; PTH (1-34) in Novasome cream). In seven treatments, the difference relative placebo was not statistically signicant: ciclopirox olamine shampoo; NG-monomethylL-arginine (L-NMMA) cream; polymyxin B cream; salicylic acid; topical sirolimus; topical tacrolimus; and tar.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid This comparison considered vitamin D analogues-potent steroid combination against potent corticosteroid (see Analysis 9.2 and Table 12). One between-patient trial reported TSS data for 966 participants. We identied no trial of scalp, nail or inverse psoriasis. Treatment duration was four weeks. The SMD for the TSS was 0.43 (95% CI: -0.56 to -0.31; I: NA).
Analysis 10: vitamin D analogues vs. dithranol This comparison considered vitamin D analogues against dithranol (see Analysis 10.2 and Table 13). Three intervention-comparator contrasts were identied: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. Three between-patient trials and 1 within-patient trial reported TSS data for 386 participants. We identied no trial of scalp, nail or inverse psoriasis. Treatment duration ranged from four weeks to eight weeks. There was some variation in the dithranol regimens employed by trials and in the baseline severity of trial participants. These factors may explain the high level of heterogeneity found in the pooled results. The SMD for the TSS was -0.27 (95% CI: -0.73 to 0.19; I: 80.1%). Data from two trials contributed to the SMD for the calcipotriol vs. dithranol: -0.54 (95% CI: -1.14 to 0.07; I: 70.3%)(Christensen 1999; Grattan 1997 (H)). Data from one trial contributed to the SMD for the tacalcitol vs. dithranol: -0.18 (95% CI: -0.60 to 0.25; I: NA)(Farkas 1999). Data from one trial contributed to the SMD for the calcitriol vs. dithranol: 0.13 (95% CI: -0.24 to 0.50; I: NA)(Hutchinson 2000). Therefore, neither the summary statistic for the TSS nor the pooled data for individual intervention-comparator contrasts provided evidence of a statistically signicant advantage of a vitamin D analogue over dithranol or vice versa.
Analysis 7: vitamin D analogues vs. corticosteroid (potent) There were eight vitamin D analogue-potent corticosteroid comparisons in Analysis 7 (see Analysis 7.2 and Table 11). Nine studies with 2334 participants reported TSS data for 6 of the 8 intervention-comparator contrasts. Five trials were between-patient design and four were within-patient studies. Two trials of scalp psoriasis were included but we identied no trial of nail or inverse psoriasis. Treatment duration ranged from three to six weeks. The SMD across all 6 treatments for TSS indicated that there was no signicant difference between the vitamin D derivates and potent corticosteroid: SMD: 0.14 (95% CI: -0.08 to 0.37; I: 85.7%). One of the six vitamin D analogues performed statistically signicantly better than the potent corticosteroid: the SMD for calcipotriol against uocinonide 0.05% ointment was -0.49 (95% CI: -0.91 to -0.06; I: NA)(Bruce 1994). In four comparisons, the vitamin D analogue was statistically signicantly less effective than the potent corticosteroid: calcipotriol vs. betamethasone dipropionate; calcipotriol vs. diorasone diacetate; calcitriol vs. betamethasone dipropionate; and tacalcitol vs. betamethasone valerate. We found no statistically signicant difference between calcipotriol and betamethasone valerate, a nding based on three studies (Duweb 2000; Klaber 1994; Kragballe 1991a).
Analysis 11: vitamin D analogues vs. coal tar Our review identied no trial comparing a vitamin D analogue against coal tar and reporting TSS data (Table 14). Analysis 12: vitamin D analogue vs. vitamin D analogue Our review identied three intervention-comparator contrasts in this comparison: calcipotriol vs. calcitriol; calcipotriol vs. tacalcitol; and calcipotriol vs. maxacalcitol (see Analysis 12.2 and Table 15). Three trials involving 388 participants contributed TSS data for all 3 of these intervention-comparator contrasts. One trial was between-patient and two were within-patient in design. Treatment duration ranged from six to eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. The SMD for the TSS indicated that there was no statistically signicant difference between the treatments: SMD: 0.09 (95% CI: -0.65 to 0.82; I: 92.6%). However, the substantial heterogeneity reected differences in the ndings from the individual intervention-comparator contrasts underlying this statistic. Calcipotriol was statistically
22
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) This comparison considered vitamin D analogues against very potent corticosteroids (see Analysis 8.2 and Table 23). We found data on one intervention-comparator contrast: calcipotriol vs. clobetasol propionate. One between-patient trial reported TSS data for 151 participants. This trial of scalp psoriasis had treatment duration of four weeks. The SMD for the TSS indicated that the very potent corticosteroid was more effective than the vitamin D analogue: 0.37 (95% CI: 0.05 to 0.69; I: NA).
signicantly less effective than calcitriol (SMD: 0.61; 95% CI: 0.28 to 0.93; the trial was of inverse psoriasis (Ortonne 2003)); more effective than tacalcitol (SMD: -0.45; 95% CI: -0.68 to 0.22) and similar in efcacy relative to maxacalcitol (SMD: 0.13; 95% CI: -0.41 to 0.68).
Analysis 17: Head-to-head: Occlusion This comparison explored the effect of adding occlusion to vitamin D analogues (see Analysis 17.2 and Table 20). One small trial of calcipotriol was identied. This was a within-patient trial with 19 participants and treatment duration of 8 weeks (Bourke 1993b). No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Calcipotriol BD plus occlusion was statistically signicant more effective than calcipotriol BD alone: the SMD for the TSS was 0.79 (95% CI: 0.13 to 1.45; I: NA). Analysis 18: vitamin D analogues vs. other treatment This comparison incorporated all other vitamin D head-to-head comparisons that had not already been included (see Analysis 18.2 and Table 21). Seven intervention-comparator contrasts were included in analysis 18, with TSS data available for 2 of these contrasts (calcipotriol vs. tacrolimus; calcipotriol vs. tazarotene). Two between-patient trials with 246 participants contributed TSS data. Treatment duration ranged from 6 to 12 weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. The comparison of calcipotriol BD against tacrolimus found a statistically signicant difference in favour of calcipotriol: SMD: -0.95 (95% CI: -1.55 to -0.34; I: NA) (Zonneveld 1998 (H)). However, the comparison of calcipotriol BD against tazarotene found no statistically signicant difference: SMD -0.05 (95% CI: -0.33 to 0.23; I: NA) (Han 2001). .
(c) Psoriasis area and severity index (PASI)
Analysis 13: Vitamin D vs. vitamin D and corticosteroid Our review identied 11 intervention-comparator contrasts, involving two vitamin D analogues, one combination product and six different corticosteroids (see Analysis 13.2 and Table 16). Two trials involving 1018 participants contributed TSS data for 2 of these 11 intervention-comparator contrasts. One trial was between-patient and one was within-patient in design. Treatment duration ranged from four to six weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, vitamin D plus corticosteroid appeared to be more effective than vitamin D alone: the SMD for the TSS was 0.80 (95% CI: 0.68 to 0.93; I: 0%). This nding applied to both intervention-comparator contrasts for which TSS data were available: calcipotriol vs. clobetasol propionate then calcipotriol (SMD: 0.63; 95% CI: 0.21 to 1.05); and calcipotriol vs. Dovobet OD (SMD: 0.82; 95% CI: 0.69 to 0.95).
Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid Our review did not identify any study providing TSS data for this comparison (Table 17).
Analysis 15: Calcipotriol vs. coal tar polytherapy This comparison involved calcipotriol against coal tar polytherapy (see Analysis 15.2 and Table 18). Three intervention-comparator contrasts were included: calcipotriol vs. coal tar, coconut oil and salicylic acid (for psoriasis of the scalp); calcipotriol vs. coal tar, allantoin and hydrocortisone cream; and calcipotriol vs. dithranol and tar. Three between-patient trials with 639 participants contributed TSS data for all three intervention-comparator contrasts. Treatment duration ranged from four to eight weeks. Two trials of scalp psoriasis were included (in both trials, TSS ndings relate only to the scalp), but no nail psoriasis or inverse psoriasis was identied. Overall, calcipotriol was statistically signicant more effective than coal tar polytherapy: the SMD for the TSS was 0.54 (95% CI: -0.90 to -0.18; I: 73.8%). Calcipotriol was statistically signicantly more effective than its comparator in each of the three intervention-comparator contrasts.
Analysis 1: vitamin D analogues vs. placebo Our review included seven vitamin D analogues in this comparison (see Analysis 1.3 and Table 6). Seven studies reported PASI data with 3203 participants contributing data on 3 of these 7 treatments. Six trials were between-patient design and one was a within-patient study. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration ranged from three weeks to eight weeks. The average effect size across all three treatments for PASI was -0.91 (95% CI: -1.18 to -0.64; I: 92.1%), but there was considerable variation between treatments with the PASI ranging from -0.66 (calcipotriol) to -1.41 (Dovobet BD). Analysis 2: Corticosteroid (potent) vs. placebo Our review included 11 potent corticosteroids in this comparison (see Analysis 2.3 and Table 7). Two studies reported PASI data from 1054 participants on once-daily and twice-daily doses of betamethasone dipropionate. Both trials had a duration of four weeks, were of between-patient design and neither study considered scalp, nail or inverse psoriasis. The average PASI effect size across both application frequencies was 1.14 (95% CI: -1.29 to 0.99; I: 0%).
23
Analysis 16: Head-to-head calcipotriol: Dosing Our review did not identify any study providing TSS data for the analysis of calcipotriol at different dosing regimens (Table 19).
Analysis 3: Corticosteroid (very potent) vs. placebo Our review did not identify any study comparing very potent corticosteroids against placebo and that reported PASI data. This may be because whole-body application of very potent corticosteroids is not recommended, so a whole-body assessment measure like the PASI is inappropriate. Analysis 4: Dithranol vs. placebo Our review did not identify any study comparing dithranol against placebo and that reported PASI data. Analysis 5: Tazarotene vs. placebo Our review did not identify any study comparing tazarotene against placebo and that reported PASI data. Analysis 6: Other treatment vs. placebo This comparison comprised all other treatments that were not included in the rst ve comparisons; therefore, pooling was removed. In total, 22 treatments are included in this analysis (see Analysis 6.3 and Table 10). Four studies with 220 participants reported PASI data on 4 of these 22 treatments. All four trials were between-patient studies. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis reported PASI data. Treatment duration ranged from 3 to 12 weeks. Three treatments performed statistically signicantly better than placebo: aloe vera SMD: -1.62(95% CI: -2.21 to -1.03)(Syed 1996); betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid: SMD: -0.54 (95% CI: -0.99 to -0.10)(Santoianni 2001); and methotrexate gel: SMD: -1.62 (95% CI: -2.21 to 1.03) (Syed 2001b). The study of Dead Sea salts emollient lotion found no statistically signicant difference relative to placebo ( Cheesbrough 1992). Analysis 7: vitamin D analogues vs. corticosteroid (potent) Our review identied eight vitamin D analogue-potent corticosteroid comparisons (see Analysis 7.3 and Table 11). Eight studies with 3033 participants reported PASI data for 4 of the 8 intervention-comparator contrasts. Six trials were between-patient design and two were within-patient studies. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis reporting PASI data for Analysis 7 was identied. Treatment duration ranged from four to eight weeks. The PASI SMD across all four intervention-comparator contrasts indicated that there was no statistically signicant difference between the vitamin D derivates and potent corticosteroid: SMD: 0.12 (95% CI: -0.09 to 0.34; I: 88.0%). One of the six vitamin D analogues performed statistically signicantly better than the potent corticosteroid: four studies contributed data to analysis of calcipotriol vs. betamethasone valerate, SMD: -0.12 (95% CI: -0.22 to -0.02; I: 0%).
In two intervention-comparator contrasts, the vitamin D analogue was statistically signicantly less effective than the potent corticosteroid: betamethasone dipropionate was more effective than both calcipotriol and calcitriol. We found no statistically signicant difference between calcipotriol and desoxymetasone. Analysis 8: vitamin D analogues vs. corticosteroid (very potent) This comparison considered vitamin D analogues against very potent corticosteroids (see Analysis 8.3 and Table 12). We found data on one intervention-comparator contrast: calcipotriol vs. clobetasol propionate. One between-patient trial reported PASI data for 40 participants. This trial had treatment duration of six weeks. The SMD for the PASI indicated that there was no statistically signicant difference between the very potent corticosteroid and the vitamin D analogue: SMD: -0.32 (95% CI: -0.95 to 0.30; I: NA). Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid This comparison considered vitamin D analogues-potent steroid combination against potent corticosteroid (Table 12). Two between-patient trials reported PASI data for 1651 participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was four weeks. The trial compared Dovobet BD with betamethasone dipropionate 0.5mg/g in the same vehicle used for the vitamin D-steroid preparation. The SMD for the PASI was 0.48 (95% CI: -0.58 to -0.38; I: 0%). Analysis 10: vitamin D analogues vs. dithranol This comparison considered vitamin D analogues against dithranol (see Analysis 10.3 and Table 13). Three intervention-comparator contrasts were identied: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. Four between-patient trials reported PASI data for 690 participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration ranged from eight to ten weeks. There was some variation in the dithranol regimens employed by trials and in the baseline severity of trial participants. These factors may explain the high level of heterogeneity found in the pooled results. The SMD for the PASI was 0.41 (95% CI: -0.47 to 1.29; I: 95.7%). Data from two trials contributed to the SMD for the calcipotriol vs. dithranol: 1.02 (95% CI: -1.71 to 3.76; I: 98.6%)(Berth Jones 1992b; Monastirli 2000). Data from one trial contributed to the SMD for the tacalcitol vs. dithranol: -0.07 (95% CI: -0.50 to 0.36; I: NA)(Farkas 1999). Data from one trial contributed to the SMD for the calcitriol vs. dithranol: -0.19 (95% CI: -0.56 to 0.18; I: NA)(Hutchinson 2000). Therefore, neither the summary statistic for the PASI nor the pooled data for
24
individual intervention-comparator contrasts provided evidence of a statistically signicant advantage of a vitamin D analogue over dithranol or vice versa.
Analysis 11: vitamin D analogues vs. coal tar Our review identied evidence for one vitamin D analogue (calcipotriol) for this comparison (see Analysis 11.3 and Table 14). Calcipotriol was compared with coal tar and white soft parafn. One within-patient trial with 27 participants reported PASI data. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Treatment duration was six weeks. The SMD for the PASI was -0.84 (95% CI: -1.39 to -0.28; I: NA).
Analysis 12: vitamin D analogue vs. vitamin D analogue Our review identied three intervention-comparator contrasts in this comparison: calcipotriol vs. calcitriol; calcipotriol vs. tacalcitol; and calcipotriol vs. maxacalcitol (see Analysis 12.3 and Table 15). One between-patient trial involving 15 participants contributed PASI data for the comparison of calcipotriol and calcitriol (Bourke 1997). Treatment duration was eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. The SMD for the PASI indicated that there was no statistically signicant difference between the treatments: SMD: -1.11 (95% CI: -2.22 to 0.01; I: NA). Results from the analysis of PASI data contrast with those from TSS data: a single study involving 75 participants found that calcitriol was statistically signicantly more effective than calcipotriol when assessed using the TSS (Ortonne 2003). In both studies, treatments were applied twice-daily, but the study by Ortonne 2003 was of inverse psoriasis.
clobetasone butyrate (Kragballe 1998b); diucortolone valerate (Salmhofer 2000); or uocinonide acetonide (Wozel 2001). In contrast, regimens involving night-time applications of betamethasone dipropionate (Ortonne 1994) or Dovobet (Guenther 2002 (H)) were statistically signicantly more effective than twicedaily calcipotriol alone. Findings for nightly betamethasone valerate (BMV) were mixed (Kragballe 1998b; Ruzicka 1998). In the study by Ruzicka 1998, BMV was applied nightly and calcipotriol in the mornings for four weeks following a two-week period with calcipotriol twicedaily, this was also found to be statistically signicantly more effective than calcipotriol applied twice-daily over six weeks (SMD: 0.70; 95% CI: 0.39 to 1.01). The eight-week study by Kragballe 1998b compared calcipotriol twice-daily with BMV at night and calcipotriol in the morning. This study found a non-signicant trend to greater effectiveness for nightly betamethasone valerate relative to twice-daily calcipotriol (SMD: 0.19; 95% CI: -0.02 to 0.40). Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid This comparison involved calcipotriol against betamethasone dipropionate with salicylic acid (see Analysis 14.3 and Table 17). One between-patient trial with 160 participants contributed PASI data. Treatment duration was six weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. We found no statistically signicant difference between the two regimens: the SMD for the PASI was -0.05 (95% CI: -0.36 to 0.26; I: NA). Analysis 15: Calcipotriol vs. coal tar polytherapy This comparison involved calcipotriol against coal tar polytherapy (see Analysis 15.3 and Table 18). Three intervention-comparator contrasts were included: calcipotriol vs. coal tar, coconut oil and salicylic acid (for psoriasis of the scalp); calcipotriol vs. coal tar, allantoin and hydrocortisone cream; and calcipotriol vs. dithranol and tar. One between-patient trial, involving 87 participants contributed PASI data for the comparison of calcipotriol and dithranol/tar (van de Kerkhof 2002a). In this study, participants applied treatments to the body and scalp, but ndings from the PASI relate only to the body. Treatment duration was four weeks. Overall, calcipotriol was statistically signicant more effective than coal tar polytherapy: the SMD for the PASI was -0.64 (95% CI: -1.07 to -0.21; I: NA). Analysis 16: Head-to-head calcipotriol: Dosing This comparison explored different dosing regimens for calcipotriol (see Analysis 16.3 and Table 19). Two intervention-comparator contrasts were included: calcipotriol BD vs. calcipotriol OD and calcipotriol BD vs. calcipotriol OM and placebo ON. One between-patient trial and one within-patient trial contributed PASI data from 475 participants. Treatment duration was eight
25
Analysis 13: Vitamin D vs. vitamin D and corticosteroid Our review identied 11 intervention-comparator contrasts, involving two vitamin D analogues, one combination product and six different corticosteroids (see Analysis 13.3 and Table 16). Eleven trials involving 4942 participants contributed PASI data for 10 of these 11 intervention-comparator contrasts. Ten trials were between-patient and one was within-patient in design. Treatment duration ranged from two to eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied, and no PASI data for the comparison of calcipotriol against clobetasol propionate then calcipotriol were identied. Overall, vitamin D plus corticosteroid appeared to be more effective than vitamin D alone: the SMD for the PASI was 0.52 (95% CI: 0.38 to 0.66; I: 83.3%). However, we found no statistically signicant difference for four intervention-comparator contrasts, all of which comprised twicedaily calcipotriol compared with a regimen with calcipotriol applied in the morning and the night-time application of a single corticosteroid: betamethasone valerate (Kragballe 1998b);
weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, we found no statistically signicant difference between once-daily and twice-daily dosing of calcipotriol, although there was a non-signicant trend in favour of twice-daily dosing: the SMD for the PASI was -0.12 (95% CI: -0.28 to 0.03; I: NA).
from four to eight weeks. The pooled effect across the three studies reporting PAGI data was -0.72 (95% CI: -1.01 to -0.42; I: 35.7%).
Analysis 2: Corticosteroid (potent) vs. placebo Our review did not identify any study comparing potent corticosteroids against placebo and that reported PAGI data.
Analysis 17: Head-to-head: Occlusion This comparison explored the effect of adding occlusion to vitamin D analogues (Table 20). Our review did not identify any relevant study that reported PASI data.
Analysis 3: Corticosteroid (very potent) vs. placebo Four very potent corticosteroids were included in this comparison for this outcome (see Analysis 3.4 and Table 8). Four studies reported PAGI data for 415 participants on three of these four treatments. There were two between-patient trials and two withinpatient studies. One trial of scalp psoriasis was included but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from two to three weeks. The SMD across all three treatments for PAGI was -1.16 (95% CI: -1.34 to -0.99; I: 0%). All three treatments performed statistically signicantly better than placebo.
Analysis 18: vitamin D analogues vs. other treatment This comparison incorporated all other vitamin D head-to-head comparisons that had not already been included (see Analysis 18.3 and Table 21). Seven intervention-comparator contrasts were included in analysis 18, with PASI data available for 4 of these contrasts: calcipotriol vs. propylthiouracil cream; calcipotriol vs. vitamin B12 cream; calcipotriol vs. Dovobet (4 wks) then vitamin D (calcipotriol) weekdays and Dovobet at the weekends (for a further 4 wks); and tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks)). Three between-patient trials and 1 within-patient trial with 1103 participants contributed PASI data. Treatment duration ranged from 8 to 12 weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. The comparison of calcipotriol BD with propylthiouracil cream found a statistically signicant difference in favour of vitamin D: SMD: -2.24 (95% CI: -3.23 to -1.25; I: NA) (Sanchez 2001). The comparison of calcipotriol BD against vitamin B12 found no statistically signicant difference: SMD -0.01 (95% CI: -0.78 to 0.75; I: NA) (Stuecker 2001). Our review found a statistically signicant difference in favour of the Dovobet/calcipotriol maintenance regimen: SMD 0.23 (95% CI: 0.07 to 0.38; I: NA) (Kragballe 2004). Similarly, the comparison of tacalcitol and calcipotriol / Dovobet found a statistically signicant difference in favour of combination maintenance therapy when assessed using the PASI: SMD: 0.78 (95% CI: 0.58 to 0.98; I: NA) (Ortonne 2004).
Analysis 4: Dithranol vs. placebo Our review did not identify any study comparing dithranol against placebo and that reported PAGI data.
Analysis 5: Tazarotene vs. placebo Our review did not identify any study comparing tazarotene against placebo and that reported PAGI data.
Analysis 6: Other treatment vs. placebo This comparison comprised all other treatments that were not included in the rst ve comparisons; therefore, pooling was removed. In total, 22 treatments are included in this analysis (see Analysis 6.4 and Table 10). Four studies with 181 participants reported PAGI data on 4 of these 22 treatments. All four trials were between-patient studies. One trial of scalp psoriasis, one of nail psoriasis and one of inverse psoriasis reported PAGI data. Treatment duration ranged from 3 to 12 weeks. Three treatments performed statistically signicantly better than placebo: betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid; ciclosporin solution in oil; and pimecrolimus cream. The SMD ranged from: -0.65 (Gribetz 2004; pimecrolimus cream) to -3.94 (ciclosporin solution in oil for nail psoriasis; Cannavo 2003). The study of ciclopirox olamine shampoo found no statistically significant difference relative to placebo when assessed using the PAGI (Shuttleworth 1998).
26
(d) Patient assessment of overall global improvement (PAGI)
Analysis 1: vitamin D analogues vs. placebo Our review included seven vitamin D analogues were included in this comparison, but PAGI data were available for one (calcipotriol) (see Analysis 1.4 and Table 6). Three studies reported PAGI data all of which were between-patient design and 488 participants contributed data. No nail or inverse psoriasis was identied and one scalp trial was included. Treatment duration ranged
Analysis 7: vitamin D analogues vs. corticosteroid (potent) Our review identied eight vitamin D analogue-potent corticosteroid comparisons (see Analysis 7.4 and Table 11). Three studies with 1206 participants reported PAGI data for 1 of these 8 intervention-comparator contrasts. Two trials were between-patient design and one was a within-patient study. One trial of scalp psoriasis, but no nail psoriasis or inverse psoriasis contributed PAGI data. Treatment duration ranged from four to six weeks. The PAGI SMD indicated that there was no statistically signicant difference between the vitamin D analogue calcipotriol and potent corticosteroid betamethasone valerate, but there was substantial heterogeneity: SMD: -0.04 (95% CI: -0.46 to 0.39; I: 94.3%).
Analysis 12: vitamin D analogue vs. vitamin D analogue Our review did not identify any study comparing vitamin D analogues head-to-head that reporting PAGI data. Analysis 13: Vitamin D vs. vitamin D and corticosteroid Our review did not identify any study comparing vitamin D compared with vitamin D plus corticosteroid that reported PAGI data. Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid This comparison involved calcipotriol against betamethasone dipropionate with salicylic acid (see Analysis 14.4 and Table 17). One between-patient trial with 186 participants contributed PAGI data. Treatment duration was six weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Calcipotriol was statistically signicantly more effective than the steroid-salicylic acid treatment: the SMD for the PAGI was -0.49 (95% CI: -0.79 to -0.20; I: NA). Analysis 15: Calcipotriol vs. coal tar polytherapy
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) Our review did not identify any study comparing vitamin D analogues against very potent corticosteroids and that reported PAGI data.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid Our review did not identify any study comparing vitamin D analogues-potent steroid combination against potent corticosteroids placebo and that reported PAGI data.
Analysis 10: vitamin D analogues vs. dithranol This comparison considered vitamin D analogues against dithranol (see Analysis 10.4 and Table 13). Three intervention-comparator contrasts were identied: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. PAGI data were available only for the intervention-comparator contrast of calcipotriol vs. dithranol. One between-patient trial reported PAGI data for 458 participants (Berth Jones 1992b). No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was eight weeks. The SMD for the PAGI was -0.47 (95% CI: -0.65 to -0.28; I: NA), indicating statistically signicant advantage for calcipotriol relative to dithranol.
This comparison involved calcipotriol against coal tar polytherapy (see Analysis 15.4 and Table 18). Three intervention-comparator contrasts were included: calcipotriol vs. coal tar, coconut oil and salicylic acid (for psoriasis of the scalp); calcipotriol vs. coal tar, allantoin and hydrocortisone cream; and calcipotriol vs. dithranol and tar. One between-patient trial, involving 87 participants contributed PAGI data for the comparison of calcipotriol and dithranol/tar (van de Kerkhof 2002a). In this study, subjects applied treatments to the body and scalp and ndings for the PAGI relate to the body and scalp. Treatment duration was four weeks. Overall, calcipotriol was statistically signicant more effective than coal tar polytherapy: the SMD for the PASI was -0.56 (95% CI: -0.99 to -0.13; I: NA). Analysis 16: Head-to-head calcipotriol: Dosing Our review did not identify any study evaluating vitamin D analogues at different doses that reported PAGI data. Analysis 17: Head-to-head: Occlusion This comparison explored the effect of adding occlusion to vitamin D analogues (Table 20). Our review did not identify any relevant study that reported PAGI data. Analysis 18: vitamin D analogues vs. other treatment This comparison incorporated all other vitamin D head-to-head comparisons that had not already been included (see Analysis 18.4 and Table 21). Seven intervention-comparator contrasts were included in analysis 18, with PAGI data available for one of these
27
Analysis 11: vitamin D analogues vs. coal tar Our review identied one vitamin D analogue (calcipotriol) for this comparison (see Analysis 11.4 and Table 14). Calcipotriol was compared with coal tar and white soft parafn. One withinpatient trial with 27 participants reported PAGI data. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Treatment duration was six weeks. The SMD for the PAGI was 1.51 (95% CI: -2.12 to -0.90; I: NA).
contrasts: calcipotriol vs. vitamin B12 cream. One within-patient trial with 13 participants contributed PAGI data. Treatment duration was 12 weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. We found no statistically significant difference between calcipotriol BD and vitamin B12 when assessed using the PAGI: SMD: -0.55 (95% CI: -1.33 to 0.24; I: NA) (Stuecker 2001). This result is identical to the IAGI ndings from the same trial.
(e) Combined endpoint (IAGI / TSS / PASI / PAGI)
Analysis 1: vitamin D analogues vs. placebo Our review included seven vitamin D analogues in this comparison (see Analysis 1.5 and Table 6). Twenty-four studies, involving 4509 participants, contributed data. Thirteen trials were between-patient design and 11 were within-patient studies. No nail or inverse psoriasis was identied and one scalp trial was included. Treatment duration ranged from 3 to 12 weeks. Treatment allocation was adequately concealed in four studies (quality rating: A). The pooled effect across all studies was -1.17 (95% CI: -1.38 to 0.96; I: 90.6%), which equates to 1.26 on a 6-point IAGI scale. However, the summary statistic conceals considerable variation between treatments with the SMD for the combined endpoint ranging from -0.82 (Tacalcitol OD; 0.88 on a 6-point point IAGI scale) to -1.90 (Dovobet BD; 2.05 on a 6-point point IAGI scale). The SMD of the combined endpoint for calcipotriol (-1.02) and calcitriol (-1.03; 1.10 and 1.11 respectively on a 6-point point IAGI scale) were similar to that of tacalcitol, whereas maxacalcitol (-1.43; 1.55 on a 6-point point IAGI scale), Dovobet OD (also 1.43) and Paricalcitol (-1.66; 1.80 on a 6-point point IAGI scale) appeared more potent than tacalcitol but less potent than Dovobet BD. However, rankings within other outcomes were not consistent: for example, the PASI results for Dovobet OD (-1.38) and Dovobet BD (-1.41) were similar. However, it may not be meaningful to look at this class as a single group given the potentially varying potency of single vitamin D and combined vitamin D/ steroid combinations and the high level of heterogeneity found in the meta analysis. It may be more informative to look at individual products within the class.
Sensitivity analyses We explored differences in within-patient and between-patient designs using one-way sensitivity analysis (Table 6). The SMD for the 11 within-patient studies (512 participants) was: -1.19 (95% CI: -1.70 to -0.69; I: 91.40%). This translates into a change of 1.29 on a 6-point IAGI scale, slightly larger than the effect size for all studies. The SMD for the 13 between-patient studies (3997 participants) was: -1.16 (95% CI: -1.39 to -0.92; I: 90.6%). This
translates into a change of 1.25 on a 6-point IAGI scale, slightly smaller than the effect size for all studies. We explored differences between trials of scalp and body psoriasis using one-way sensitivity analysis (Table 6). The SMD for the single scalp trial (Green 1994; 49 participants) was: -1.09 (95% CI: -1.69 to -0.48). This translates into a change of 1.17 on a 6point IAGI scale, slightly smaller than the pooled value with all trials. The SMD for the remaining 23 studies (4485 participants) was: -1.17 (95% CI: -1.39 to -0.95; I: 91.0%). This translates into a change of 1.26 on a 6-point IAGI scale, identical to the pooled value for all studies. The scalp trial evaluates calcipotriol against placebo. For the pooled analysis of this subgroup without the scalp trial (i.e. the remaining 14 calcipotriol studies), the SMD differed very slightly from the pooled value with the scalp trial: 1.02 (95% CI: -1.22 to -0.82; I: 77.9%), compared with -1.02 (95% CI: -1.21 to -0.83; I: 76.3%). The study by Perez 1996 comparing calcitriol and placebo reported large and statistically signicant differences for both TSS and IAGI outcomes. In both outcomes, the magnitude of the effect was the largest across all comparisons, outcomes and treatments. Perez 1996 is a 10-week within-patient study involving 84 participants. The study included persons with severe disease (mean TSS at baseline: 7.6 on a 10-point scale, with at least 10% of body surface area affected) who had previously had an unsatisfactory response to at least 1 previous treatment including topical steroids, UVB, PUVA and methotrexate. The dramatic improvement observed in the intervention group is difcult to interpret in the context of ndings from other trials and we explored the impact of removing this study in sensitivity analysis. When we removed Perez 1996 from the pooled analysis for calcitriol, the effect size was smaller but statistically signicantly different from placebo: SMD with Perez 1996 (5 studies): -1.03 (95% CI: -2.25 to 0.19; I: 95.4%); SMD without Perez 1996 (4 studies): -0.56 (95% CI: -0.96 to -0.16; I: 0%). On a 6-point point IAGI scale, these effect sizes equate to 1.11 and 0.60 respectively (Table 6). The trials of calcipotriol varied by dose, treatment duration and dosing frequency; where trials reported more than one dose (Kragballe 1988b) or vehicle (Harrington 1996a), the weighted mean and standard deviation across the trial was estimated. The effect size for twice-daily regimens (12 trials) was -1.06 (95% CI: -1.26 to -0.86; I: 63.7%); this equates to 1.14 on a 6-point IAGI scale. For once-daily calcipotriol studies (3 trials), the corresponding gures were -0.89 (95% CI: -1.37 to -0.40; I: 88.9%); 0.96 on a 6-point IAGI scale. Therefore, both dosing frequencies were more effective than placebo but once-daily applications had a slightly smaller effect (Table 6).
Analysis 2: Corticosteroid (potent) vs. placebo Our review identied 11 potent corticosteroids in this comparison (see Analysis 2.5 and Table 7). The treatments included three betamethasone dipropionate regimens, but we identied
28
no effectiveness evidence for budesonide and no study reporting PAGI data. Therefore, 17 studies involving 2386 participants contributed data on 10 of the 11 treatments. Fifteen trials were between-patient design and two were within-patient studies. Four studies received a quality rating of A. No nail or inverse psoriasis was identied but three scalp trials were included. Treatment duration ranged from 2 to 12 weeks. Participant numbers for individual studies ranged from 9 (Wortzel 1975 (2)) to 633 (Kaufmann 2002 (P)) and the number of studies contributing data for an individual treatment ranged from 1 (6 treatments) to 5 (betamethasone dipropionate BD). The pooled effect across all studies was 0.95 (95% CI: -1.11 to -0.80; I: 61.1%). This equates to 1.03 on a 6-point IAGI scale. Effect sizes for individual treatments ranged from -0.34 (diorasone diacetate OD) to -1.34 (betamethasone dipropionate BD), or 0.36 to 1.44 on a 6-point IAGI scale. With the exception of diorasone diacetate (Lane 1983), all potent corticosteroids were found to be statistically signicantly more effective than placebo at the 5% level.
The SMD across all three treatments was -1.29 (95% CI: -1.45 to -1.13; I: 53.2%). This equates to 1.39 on a 6-point IAGI scale. All four treatments performed statistically signicantly better than placebo.
Sensitivity analyses We explored differences in within-patient and between-patient designs using one-way sensitivity analysis (Table 8). The SMD for the 3 within-patient studies (231 participants) was: -1.23 (95% CI: -1.43 to -1.04; I: 0%). This translates into a change of 1.33 on a 6-point IAGI scale, which is slightly smaller than the effect for all studies. The SMD for the 8 between-patient studies (1340 participants) was: -1.31 (95% CI: -1.53 to -1.10; I: 65.0%). This translates into a change of 1.42 on a 6-point IAGI scale, which is slightly larger than the effect for all studies. We also explored differences between trials of scalp and body psoriasis using one-way sensitivity analysis (Table 8). Five trials of scalp psoriasis were included in this analysis (Ellis 1988; Franz 2000; Jarratt 2004; Olsen 1991; Lepaw 1978). The SMD for the pooled scalp trials (866 participants) was: -1.33 (95% CI: -1.59 to -1.08; I: 61.0%). This translates into a change of 1.44 on a 6point IAGI scale, which is slightly higher than the pooled value with all trials. The analysis of 6 non-scalp trials (705 participants) was: -1.24 (95% CI: -1.43 to -1.04; I: 38.2%). This translates into a change of 1.34 points on a 6-point IAGI scale, which is very similar to the pooled value for all studies. Analysis 4: Dithranol vs. placebo This comparison considered dithranol against placebo (see Analysis 4.5 and Table 9). Three within-patient trials reported data for 47 participants, 1 of which reported IAGI data and all reported TSS data. The types of treatment comprised: dithranol 0.1% in a carbamide (17% urea) base BD (Buckley 1978); dithranol in aqueous gel, (dose titration 0.1-2.0%), BD (Grattan 1997 (P)); and dithranol 2% ointment one minute therapy, OD (Jekler 1992). Treatment duration ranged from three to eight weeks. In all three studies, the adequacy of the concealment of treatment allocation was unclear. No trial of scalp, nail or inverse psoriasis was identied. The SMD for the combined endpoint was -1.05 (95% CI: 1.65 to -0.46; I: 36.8%). This equates to 1.14 on a 6-point IAGI scale. All trials individually found a statistically signicant effect in favour of dithranol. Analysis 5: Tazarotene vs. placebo This comparison considered tazarotene against placebo (see Analysis 5.5 and Table 22). One between-patient trial was identied, which assessed tazarotene OD at 0.1% and 0.05% strengths (we estimated the average outcome across these doses). Weinstein
29
Sensitivity analyses We explored differences in within-patient and between-patient designs using one-way sensitivity analysis (Table 7). The SMD for the two within-patient studies was: -1.34 (95% CI: -1.78 to 0.89; I: 0%). This translates into a change of 1.44 on a 6-point IAGI scale, which is larger than the effect for all studies. However, as just 48 participants contributed data to this analysis, robust inferences cannot be drawn. The SMD for the 15 between-patient studies (2338 participants) was: -0.92 (95% CI: -1.09 to -0.76; I: 62.8%). This translates into a change of 1.00 on a 6-point IAGI scale, slightly smaller than the effect for all studies. We also explored differences between trials of scalp and body psoriasis using one-way sensitivity analysis (Table 7). Three trials of scalp psoriasis were included in this analysis (Elie 1983; Franz 1999; Pauporte 2004). The SMD for the pooled scalp trials (276 participants) was: -1.16 (95% CI: -1.43 to -0.90; I: 0%). This translates into a change of 1.26 on a 6-point IAGI scale, which is higher than the pooled value with all trials. The analysis of 14 non-scalp trials (2158 participants) was: -0.92 (95% CI: -1.10 to -0.74; I: 65.5%). This translates into a change of 0.99 points on a 6-point IAGI scale, which is very similar to the pooled value for all studies. Analysis 3: Corticosteroid (very potent) vs. placebo Our review identied four very potent corticosteroids in this comparison (see Analysis 3.5 and Table 8). Eleven studies reported data for 1571 participants. There were eight between-patient trials and three within-patient studies. Five trials of scalp psoriasis were included but no trial of nail or inverse psoriasis was identied. Treatment duration ranged from two to four weeks. In no study was treatment allocation adequately concealed (quality rating: A).
1996 reported TSS data for 318 participants, but IAGI, PASI and PAGI scores were not assessed. The study did not assess psoriasis of the scalp, nail or exural areas. Treatment duration was 12 weeks and the adequacy of concealment of treatment allocation was unclear. As only one trial reporting one outcome measure contributed data to the analysis, the SMD for the combined endpoint was identical to that of the TSS (i.e. -0.91 (95% CI: -1.16 to -0.67; I: NA). This equates to 0.98 on a 6-point IAGI scale. Three additional studies comparing tazarotene and placebo were identied, but none reported useable effectiveness data and so contributed only to the analysis of withdrawals and adverse events (Krueger 1998; Scher 2001 (nail psoriasis); Weinstein 2003).
ing the TSS (-0.77; 95% CI: -1.40 to -0.14) whereas the difference assessed by the IAGI was not (-0.02; 95% CI: -0.63 to 0.58). Lastly, salicylic acid was not statistically signicantly different to placebo when assessed by the TSS (-0.59; 95% CI: -1.49 to 0.31), whereas the difference assessed by the IAGI was of borderline statistical signicance (-0.96; 95% CI: -1.89 to -0.02).
Analysis 7: vitamin D analogues vs. corticosteroid (potent) Our review identied eight vitamin D analogue-potent corticosteroid comparisons for this comparison (see Analysis 7.5 and Table 11). Fifteen studies with 3900 participants reported data for these 8 intervention-comparator contrasts. Ten trials were between-patient design and ve were within-patient studies. Two trials of scalp psoriasis, but no nail psoriasis or inverse psoriasis contributed effectiveness data. Treatment duration ranged from three to eight weeks. In one study, treatment allocation was adequately concealed (Papp 2003 (H)). The combined endpoint SMD indicated that, overall, there was no statistically signicant difference between the vitamin D derivate calcipotriol and potent corticosteroids: SMD: 0.08 (95% CI: 0.07 to 0.24; I: 80.6%). There was, however, substantial heterogeneity and variation in effect underlying this summary statistic. The difference between the vitamin D analogue and the potent corticosteroid was not statistically signicant for ve intervention-comparator contrasts (calcipotriol vs. betamethasone dipropionate; calcipotriol vs. betamethasone valerate; calcipotriol vs. desoxymetasone; calcitriol vs. betamethasone dipropionate; calcitriol vs. betamethasone valerate). In one intervention-comparator contrast (calcipotriol vs. uocinonide), the vitamin D analogue was signicantly more effective: SMD: -0.58 (05%CI: 0.99 to -0.18; I: NA), equivalent to 0.64 on a 6-point IAGI scale. In two intervention-comparator contrasts, the potent corticosteroid was signicantly more effective than the vitamin D analogue (calcipotriol vs. diorasone diacetate; tacalcitol vs. betamethasone valerate). The SMD effect sizes for these were 0.27 and 0.41 respectively, equivalent to an improvement of 0.29 and 0.45 on a 6-point IAGI scale.
Analysis 6: Other treatment vs. placebo This comparison comprised all other treatments that were not included in the rst ve comparisons; therefore, pooling was removed. In total, 22 treatments are included in this analysis (see Analysis 6.5 and Table 10). Twenty-one studies, with 741 participants, reported data on 21 of these 22 treatments. The study of omega-3-polyunsaturated fatty acids ointment (Henneicke-v. Z. 1993) did not provide useable effectiveness data, but contributed data to the analysis of withdrawals. Eleven trials were betweenpatient design and ten were within-patient studies. Three trials of scalp psoriasis, one trial of nail psoriasis and one trial of inverse psoriasis were included in this analysis. Treatment duration ranged from 3 to 12 weeks. In two studies, treatment allocation was adequately concealed (Gribetz 2004; Stutz 1996). As assessed by the combined endpoint, eleven treatments performed statistically signicantly better than placebo: aloe vera cream; anti IL-8 monoclonal antibody cream; betamethasone17,21-dipropionate plus salicylic acid; ciclosporin solution in oil (for psoriasis of the nails); sh oil plus occlusion; methotrexate gel; mycophenolic acid ointment; pimecrolimus cream; PTH (134) in Novasome cream; and salicylic acid. The effect size for the combined endpoint ranged from -0.59 (Jin 2001; anti IL-8 monoclonal antibody cream) to -2.31 (Holick 2003; PTH (1-34) in Novasome cream), or 0.64 to 2.49 respectively on a 6-point IAGI scale. In ten treatments, the difference relative to placebo using the combined endpoint was not statistically signicant. These included ciclopirox olamine shampoo; Dead Sea salts emollient lotion; hexauoro-1,25-dihydroxyvitamin D3; NG-monomethyl-L-arginine (L-NMMA) cream; oleum horwathiensis; platelet aggregation activating factor (PAF); polymyxin B cream; topical sirolimus; topical tacrolimus; and tar. In three treatments, ndings by different outcomes were inconsistent. When assessed by the TSS, hexauoro-1,25-dihydroxyvitamin D3 was signicantly more effective than placebo (-1.13; 95% CI: -1.91 to -0.35) whereas the difference assessed by the IAGI was non-signicant (-0.62; 95% CI: -1.35 to 0.12). Similarly, the difference for oleum horwathiensis was statistically signicant us-
Sensitivity analyses We explored differences in within-patient and between-patient designs using one-way sensitivity analysis (Table 11). The SMD for the 5 within-patient studies (554 participants) was 0.17 (95% CI: -0.20 to 0.53; I: 81.7%). The SMD for the 10 betweenpatient studies (3346 participants) was -0.06 (95% CI: -0.11 to 0.23; I: 79.0%). Although these statistics were slightly different from the analysis of all trials, the difference of vitamin D relative to potent corticosteroid was consistently non-signicant. We also explored differences between trials of scalp and body psoriasis using one-way sensitivity analysis (Table 11). Two trials of
30
scalp psoriasis were included in this analysis, both of which compared calcipotriol against betamethasone valerate (Klaber 1994; Duweb 2000). The pooled SMD for the 2 scalp trials (510 participants) was 0.37 (95% CI: 0.20 to 0.55; I: 0%), which is a statistically signicant difference in favour of the potent corticosteroid. This translates into a change of 0.40 on a 6-point IAGI scale, which is higher than the pooled value with all trials evaluating calcipotriol against betamethasone valerate (SMD: 0.02 (95% CI: -0.22 to 0.25; I: 83.1%, or 0.02 points on a 6-point IAGI scale). The analysis of 13 non-scalp trials (3390 participants) found no evidence of a statistically signicant difference: SMD: 0.04 (95% CI: -0.12 to 0.21; I: 80.5%).
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) This comparison considered vitamin D analogues against very potent corticosteroids (see Analysis 8.5 and Table 23). We found data on one intervention-comparator contrast: calcipotriol vs. clobetasol propionate. Two between-patient trials reported data for 191 participants. There was one trial of scalp psoriasis, but no trial of nail or inverse psoriasis was identied for this analysis. Treatment duration ranged between four and six weeks. In one study, treatment allocation was adequately concealed (Landi 1993). The SMD for the combined endpoint indicated that there was no statistically signicant difference between the very potent corticosteroid and the vitamin D analogue: 0.08 (95% CI: -0.60 to 0.75; I: 73.5%).
vs. dithranol; and calcitriol vs. dithranol. Six between-patient trials and 1 within-patient trial reported data for 1198 participants. No trial of scalp, nail or inverse psoriasis was identied and in no trial was concealment of treatment allocation considered to be adequate. Treatment duration ranged from 4 weeks to 12 weeks. In addition, there was some variation in the dithranol regimens employed by trials and in the baseline severity of trial participants. These factors may explain the high level of heterogeneity found in the pooled results. The SMD for the combined endpoint was 0.04 (95% CI: -0.53 to 0.61; I: 95.2%), indicating that there was no evidence of a statistically signicant difference in effect between vitamin D analogues and dithranol. However, the high level of heterogeneity means that this estimate should be treated with caution. The study of 114 participants comparing calcitriol against dithranol (Hutchinson 2000) found a statistically signicant difference in favour of dithranol: SMD: 0.51 (95% CI: 0.14 to 0.88; I: NA). This equates to a 0.56 point improvement on a 6-point IAGI scale.
Analysis 11: vitamin D analogues vs. coal tar We found evidence for one vitamin D analogue (calcipotriol) for this comparison (see Analysis 11.5 and Table 14). Calcipotriol was compared with coal tar and with coal tar and white soft parafn. Two trials, 1 between-patient and 1 within-patient, with 57 participants reported data. Treatment duration was six weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. In no study was the concealment of treatment allocation demonstrably adequate. In all comparisons and all outcome assessments, calcipotriol was statistically signicantly more effective than coal tar. The SMD for the combined endpoint was -1.13 (95% CI: -1.60 to -0.67; I: 0%), which equates to 1.24 points on a 6-point IAGI scale. The effect sizes for the comparison against coal tar alone (SMD: 1.01; 95% CI: -1.77 to -0.24) and against coal tar and white soft parafn (SMD: -1.21; 95% CI: -1.79 to -0.62) were similar. These effect sizes translate into 1.10 and 1.32 points respectively on a 6point IAGI scale.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid This comparison considered vitamin D analogues-potent steroid combination against potent corticosteroid (see Analysis 9.5 and Table 12). Two between-patient trials reported data for 1698 participants. No trial of scalp, nail or inverse psoriasis was identied. Treatment duration was four weeks. In neither study was treatment allocation adequately concealed. The trial compared Dovobet BD with betamethasone dipropionate 0.5 mg/g in the same vehicle used for the vitamin D-steroid preparation. The SMD for the combined endpoint was -0.44 (95% CI: -0.54 to -0.35; I: 0%), indicating that calcipotriol combined with betamethasone dipropionate was statistically signicantly more effective than betamethasone dipropionate alone when both treatments were used twice-daily. This difference equates to 0.48 on a 6-point IAGI scale.
Analysis 12: vitamin D analogue vs. vitamin D analogue Our review identied three intervention-comparator contrasts in this comparison: calcipotriol vs. calcitriol; calcipotriol vs. tacalcitol; and calcipotriol vs. maxacalcitol (see Analysis 12.5 and Table 15). Four trials involving 342 participants contributed data. Two trials were within-patient and two between-patient in design and in none was the concealment of treatment allocation demonstrated to be adequate. Treatment duration ranged from six to eight weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. The SMD for the combined endpoint indicated that there was no statistically signicant difference between the treatments: SMD: 31
Analysis 10: vitamin D analogues vs. dithranol This comparison considered vitamin D analogues against dithranol (see Analysis 10.5 and Table 13). Three intervention-comparator contrasts were identied: calcipotriol vs. dithranol; tacalcitol
0.05 (95% CI: -0.76 to 0.67; I: 90.4%). When individual intervention-comparator contrasts are considered using the combined endpoint, calcipotriol was more effective than tacalcitol (SMD: 0.47; 95% CI -0.73 to -0.21), which equates to an improvement of 0.51 on a 6-point IAGI scale. However, there was no statistically signicant difference between calcipotriol and calcitriol (SMD: 0.16; 95% CI -1.83 to 1.51; I: 88.0%), or between calcipotriol and maxacalcitol (SMD: 0.43; 95% CI -0.12 to 0.98; I: NA). Treatments were applied twice-daily in all trials, with the exception of tacalcitol which was applied once-daily (Veien 1997).
We explored differences in within-patient and between-patient designs using one-way sensitivity analysis (Table 16). The SMD for the two within-patient studies was: 0.33 (95% CI: -0.18 to 0.84; I: 70.5%), suggesting the difference between vitamin D and the combined vitamin D-corticosteroid products was not statistically signicant. However, as only 2 trials with 104 participants contributed data to this nding, its interpretation is unclear. The SMD for the 10 between-patient studies (4538 participants) was: 0.52 (95% CI: 0.36 to 0.68; I: 86.7%), which equates to 0.57 on a 6-point IAGI scale. Unsurprisingly, this nding was consistent with the analysis that included both within- and between-patient trials.
Analysis 13: Vitamin D vs. vitamin D and corticosteroid Our review identied 11 intervention-comparator contrasts, involving two vitamin D analogues, one combination product and six different corticosteroids (see Analysis 13.5 and Table 16). Twelve trials involving 5041 participants contributed data. Ten trials were between-patient and two were within-patient in design. Treatment duration ranged from two to eight weeks. In three trials, treatment allocation was adequately concealed (quality rating: A). No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, vitamin D plus corticosteroid appeared to be more effective than vitamin D alone: the SMD for the combined endpoint was 0.50 (95% CI: 0.35 to 0.65; I: 85.5%), which translates into 0.55 on a 6-point IAGI scale. However, we found no statistically signicant difference for three intervention-comparator contrasts, all of which involved twicedaily calcipotriol compared with a regimen with calcipotriol applied in the morning and night-time application of a single corticosteroid: clobetasone butyrate (Kragballe 1998b); diucortolone valerate (Salmhofer 2000); or uocinonide acetonide (Wozel 2001). In contrast, regimens involving night-time applications of betamethasone valerate (Ruzicka 1998; Kragballe 1998b); betamethasone dipropionate (Ortonne 1994); or Dovobet (Guenther 2002 (H)) were statistically signicantly more effective than twice-daily calcipotriol alone. A regimen of clobetasol propionate ointment, 0.05% twice-daily for 2 weeks followed by calcipotriol twice-daily for 4 weeks was statistically signicantly more effective than calcipotriol twice-daily over 6 weeks (Austad 1998). Twice-daily calcipotriol was signicantly less effective than Dovobet when applied twice-daily (Douglas 2002; Guenther 2002 (H); Papp 2003 (H)) or once-daily (Kragballe 2004). Unsurprisingly, once-daily Dovobet was also signicantly more effective than once-daily calcipotriol (Kaufmann 2002 (H)). Once-daily tacalcitol for eight weeks found to be statistically signicantly less effective than a four-week treatment with nightly Dovobet, followed by four-week treatment with nightly calcipotriol (Ortonne 2004).
Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid This comparison involved calcipotriol against betamethasone dipropionate with salicylic acid (see Analysis 14.5 and Table 17). Two between-patient trials with 360 participants contributed data. Treatment duration was six weeks and in no trial was the concealment of treatment allocation demonstrated to be adequate. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, we found no statistically signicant difference between the two regimens: the SMD for the combined endpoint was -0.05 (95% CI: -0.26 to 0.15; I: 0%). The study by Scarpa 1994 found a statistically signicant difference in favour of calcipotriol when assessed using the PAGI (SMD: -0.49; 95% CI: -0.79 to-0.20); however, the investigator assessment in the same study found the difference to be non-signicant (IAGI SMD: 0.06; 95% CI: -0.33 to 0.22).
Analysis 15: Calcipotriol vs. coal tar polytherapy This comparison involved calcipotriol against coal tar polytherapy (see Analysis 15.5 and Table 18). Three intervention-comparator contrasts were included: calcipotriol vs. coal tar, coconut oil and salicylic acid (for psoriasis of the scalp); calcipotriol vs. coal tar, allantoin and hydrocortisone cream; and calcipotriol vs. dithranol and tar. Three between-patient trials with 626 participants contributed data for all 3 intervention-comparator contrasts. Treatment duration ranged from four to eight weeks and all three trials were open (participants and investigators were not masked to treatment allocation). Two trials of scalp psoriasis were included (one of which also treated and assessed the body; van de Kerkhof 2002a), but no nail psoriasis or inverse psoriasis was identied. Overall, calcipotriol was statistically signicant more effective than coal tar polytherapy: the SMD for the combined endpoint was 0.52 (95% CI: -0.68 to -0.36; I 0%), which equates to 0.57 on a 6-point IAGI scale. Calcipotriol was statistically signicantly more effective than its comparator in each of the three interventioncomparator contrasts.
32
Sensitivity analyses
Analysis 16: Head-to-head calcipotriol: Dosing This comparison explored different dosing regimens for calcipotriol (see Analysis 16.5 and Table 19). Two intervention-comparator contrasts were included: calcipotriol BD vs. calcipotriol OD; and calcipotriol BD vs. calcipotriol OM and placebo ON. One between-patient trial and one within-patient trial contributed data from 474 participants. Treatment duration was eight weeks in both trials and in neither trial was concealment of treatment allocation demonstrated to be adequate. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Overall, twicedaily calcipotriol was statistically signicant more effective than once-daily calcipotriol: the SMD for the combined endpoint was -0.19 (95% CI: -0.37 to -0.02; I: 12.0%), which equates to 0.21 on a 6-point IAGI scale. However, ndings from individual intervention-comparator contrasts underlying this statistic were mixed. In the study comparing calcipotriol BD and OD, we found no statistically signicant difference (SMD: -0.10; 95% CI: -0.34 to 0.15)(Baiocchi 1997). In the study comparing calcipotriol BD with calcipotriol OM and placebo ON, the difference was statistically signicant in favour of twice-daily dosing (SMD: -0.27; 95% CI: -0.48 to -0.06)(Kragballe 1998b).
treatment allocation was demonstrated to be adequate (Kragballe 2004). Treatment duration ranged from 6 to 12 weeks. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Statistically signicant differences in favour of the vitamin D analogue were found in the comparison of twice-daily calcipotriol ointment with propylthiouracil cream and tacrolimus ointment: SMD: -2.24 (95% CI: -3.23 to -1.25; I: NA), a difference equating to 2.45 points on a 6-point IAGI scale. Statistically signicant differences in favour of the comparator treatment were found in the comparison of calcipotriol against a Dovobet/calcipotriol maintenance regimen (effect size: 0.23, equivalent to 0.25 points on a 6-point IAGI) and in the comparison of tacalcitol against a different calcipotriol/Dovobet maintenance regimen (effect size: 0.78, equivalent to 0.85 points on a 6-point IAGI). We found no statistically signicant difference in the comparison of calcipotriol against tazarotene or against vitamin B12 . (2) Secondary outcome measures
(a) Withdrawal rates (total rate; withdrawal due to adverse events; withdrawal due to treatment failure)
Analysis 17: Head-to-head: Occlusion This comparison explored the effect of adding occlusion to vitamin D analogues (see Analysis 17.5 and Table 20). One small trial of calcipotriol was identied. This was a within-patient trial with 19 participants and treatment duration of 8 weeks (Bourke 1993b). Concealment of treatment allocation was not demonstrated to be adequate. No trial of scalp psoriasis, nail psoriasis or inverse psoriasis was identied. Only TSS data were available for this analysis. Calcipotriol BD plus occlusion was statistically signicantly more effective than calcipotriol BD alone: the SMD for the combined endpoint was 0.79 (95% CI: 0.13 to 1.45; I: NA) which equates to 0.86 on a 6-point IAGI scale. Analysis 1: vitamin D analogues vs. placebo We pooled withdrawal data from seven vitamin D analogues using a random effects risk difference (RD) metric (see Analysis 1.6, Analysis 1.7 and Analysis 1.8). Overall, withdrawals from the trials for any reason (total withdrawals) were slightly less frequent in the vitamin D group: RD: -0.03 (95% CI: -0.06 to -0.01; I: 55.6%). Rates of withdrawals due to adverse events were not statistically signicantly different (RD: -0.02 (95% CI: -0.05 to 0.00; I: 75.7%)), but withdrawals due to treatment failure were statistically lower in the treatment group (RD: -0.05 (95% CI: -0.10 to -0.01; I: 91.6%)). Compared with placebo, calcipotriol, Dovobet OD and Dovobet BD had statistically signicantly lower total withdrawal rates and withdrawal rates due to treatment failure. Withdrawal rates due to adverse events were signicantly lower for calcipotriol (RD: -0.02 (95% CI: -0.04 to -0.00; I: 11.9%)), Dovobet OD (RD: -0.09 (95% CI: -0.12 to -0.06; I: 3.7%)) and Dovobet BD (RD: -0.10 (95% CI: -0.14 to -0.05; I: NA)). Our review found no other statistically signicant differences relative to placebo. Analysis 2: Corticosteroid (potent) vs. placebo Withdrawal data for two corticosteroids were not available (diorasone diacetate; uticasone propionate). We pooled data from 9 of the 11 potent corticosteroids using a random effects risk difference metric (see Analysis 2.6, Analysis 2.7 and Analysis 2.8). Overall, there was a small but statistically signicant difference in favour of potent corticosteroids for withdrawals from the trials
33
Analysis 18: vitamin D analogues vs. other treatment This comparison incorporated all other vitamin D head-to-head comparisons that had not already been included (see Analysis 18.5 and Table 21). Seven intervention-comparator contrasts were included in analysis 18, with data available for 6 of these contrasts: calcipotriol vs. propylthiouracil cream; calcipotriol vs. tacrolimus ointment; calcipotriol vs. tazarotene gel; calcipotriol vs. vitamin B12 cream; calcipotriol vs. Dovobet (4 weeks) then vitamin D (calcipotriol) weekdays and Dovobet at the weekends (for a further 4 weeks); and tacalcitol vs. calcipotriol (4 weeks) then Dovobet (4 weeks)). No effectiveness data on the comparison of calcipotriol vs. tazarotene gel plus mometasone furoate were available, but withdrawal data were reported. Five between-patient trials and one within-patient trial with 1349 participants contributed data for the combined endpoint. In one of the six studies, concealment of
for any reason (total withdrawals): RD: -0.07 (95% CI: -0.13 to -0.01; I: 63.7%). Withdrawals due to adverse events were not statistically signicantly different relative to placebo (RD: -0.01 (95% CI: -0.04 to 0.02; I: 56.1%)). For the rate of withdrawals due to treatment failure (Analysis 2.8), ndings differed by treatment duration. For short-term treatments, there was no difference relative to placebo (RD: 0.00 ( 95% CI -0.02 to 0.02; I: 0.0%)). This is the pooled effect for the placebo comparisons with betamethasone valerate, budesonide, desonide and hydrocortisone buteprate. For maintenance treatment with betamethasone dipropionate, there was a statistically signicant difference in favour of maintenance treatment when compared with placebo: RD: 0.46 (95% CI -0.61 to -0.31; I: 0.0%). Compared with placebo, betamethasone dipropionate OD was associated with statistically signicantly lower rates for total withdrawal and for withdrawal due to adverse events. Withdrawal due to treatment failure was signicantly lower only for potent corticosteroid as maintenance therapy. Our review found no other statistically signicant differences relative to placebo in the remaining comparisons of withdrawals in this analysis. Analysis 3: Corticosteroid (very potent) vs. placebo We identied withdrawal data for all four very potent corticosteroids and pooled data using a random effects risk difference metric (see Analysis 3.6, Analysis 3.7 and Analysis 3.8). Overall, there were no statistically signicant differences between very potent corticosteroids and placebo for any type of withdrawal or for any individual treatment. For total withdrawals, the risk difference was -0.02 (95% CI: -0.06 to 0.02; I: 76.1%). Differences in withdrawals due to adverse events (RD: -0.00 (95% CI: -0.01 to 0.01; I: 0.0%)) and withdrawals due to treatment failure (RD: -0.01 (95% CI: -0.04 to 0.01; I: 75.4%)) were also small and nonsignicant. Analysis 4: Dithranol vs. placebo We pooled withdrawal data on dithranol vs. placebo using a random effects risk difference metric (see Analysis 4.6, Analysis 4.7 and Analysis 4.8). Overall, there were no statistically signicant differences between dithranol and placebo for any type of withdrawal. For total withdrawals, the risk difference was 0.00 (95% CI: -0.09 to 0.09; I: NA). Differences in withdrawals due to adverse events (RD: 0.00 (95% CI: -0.05 to 0.05; I: NA)) and withdrawals due to treatment failure (RD: 0.00 (95% CI: -0.11 to 0.11; I: NA)) were also small and nonsignicant. Analysis 5: Tazarotene vs. placebo We pooled data from the two trials of tazarotene using a random effects risk difference (RD) metric (see Analysis 5.6, Analysis 5.7 and Analysis 5.8). Relative to placebo, there was no difference in total withdrawals for tazarotene: RD: 0.04 (95% CI: -0.01 to
0.09; I: 0.0%). Rates of withdrawals due to adverse events were statistically signicantly different in favour of placebo (RD: 0.07 (95% CI: 0.05 to 0.10; I: 0.0%), but there was no signicant difference for withdrawals due to treatment failure (RD: -0.02 (95% CI: -0.04 to 0.01; I: 0.0%)).
Analysis 6: Other treatment vs. placebo We report ndings separately for 20 of the 22 comparisons considered; withdrawal data were not available for placebo comparisons involving topical sirolimus or coal tar. Data on total withdrawals were available for 18 analyses; for withdrawals due to adverse events and withdrawals due to treatment failure, the corresponding gures were 17 and 15 respectively (see Analysis 6.6, Analysis 6.7 and Analysis 6.8). We assessed withdrawal data using a random effects risk difference metric. The only statistically signicant difference found was for the comparison of tacrolimus ointment with placebo: tacrolimus was statistically signicantly less likely to be associated with withdrawal due to treatment failure or withdrawal for any reason (total withdrawals).
Aloe vera extract Sixty participants contributed data (Syed 1996). The comparison with placebo found no statistically signicant difference for aloe vera extract, for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Anti IL-8 monoclonal antibody cream Ninety-six participants contributed data (Jin 2001). The comparison with placebo found no statistically signicant difference for anti IL-8 monoclonal antibody cream or withdrawals due to adverse events. Data on total withdrawals and withdrawals due to treatment failure were not reported.
Betamethasone-17,21-dipropionate plus salicylic acid Withdrawal data on this product related to scalp psoriasis. Twenty participants contributed data (Elie 1983). The comparison with placebo found no statistically signicant difference for betamethasone-17, 21-dipropionate plus salicylic acid for total withdrawals. Data on withdrawals due to adverse events and withdrawals due to treatment failure were not reported.
Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid

34
Eighty-ve participants contributed data (Santoianni 2001). The comparison with placebo found no statistically signicant difference for betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Mycophenolic acid ointment Fourteen participants contributed data (Geilen 2000). The comparison with placebo found no statistically signicant difference for mycophenolic acid ointment for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Ciclopirox olamine shampoo This product is for scalp psoriasis. Forty participants contributed data (Shuttleworth 1998). The comparison with placebo found no statistically signicant difference for ciclopirox olamine shampoo for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. Ciclosporin solution in oil. This product is for nail psoriasis. Sixteen participants contributed data (Cannavo 2003). Relative to placebo, we found no statistically signicant difference for ciclosporin solution in oil for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. NG-monomethyl-L-arginine (L-NMMA) cream Thirty-four participants contributed data (Ormerod 2000). The comparison with placebo found no statistically signicant difference for NG-monomethyl-L-arginine (L-NMMA) cream for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Oleum horwathiensis Dead Sea salts emollient lotion Twenty-four participants contributed data (Cheesbrough 1992). The comparison with placebo found no statistically signicant difference for Dead Sea salts emollient lotion for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. Fifty participants contributed data (Lassus 1991). The comparison with placebo found no statistically signicant difference for oleum horwathiensis for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Omega-3-polyunsaturated fatty acids ointment Fish oil plus occlusion Fifty participants contributed data (Escobar 1992). The comparison with placebo found no statistically signicant difference for sh oil plus occlusion for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. One hundred and forty-six participants contributed data ( Henneicke-v. Z. 1993). The comparison with placebo found no statistically signicant difference for omega-3-polyunsaturated fatty acids ointment for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Hexauoro-1,25-dihydroxyvitamin D3 Thirty participants contributed data (Durakovic 2001). The comparison with placebo found no statistically signicant difference for hexauoro-1, 25-dihydroxyvitamin D3 for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Pimecrolimus cream, 1% BD Fifty-seven participants contributed data (Gribetz 2004). The comparison with placebo found no statistically signicant difference for pimecrolimus cream for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Methotrexate gel Sixty participants contributed data (Syed 2001b). The study by Sutton 2001 on methotrexate gel did not report withdrawal data. The comparison with placebo found no statistically signicant difference for methotrexate gel for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Platelet aggregation activating factor (PAF)(Ro 24-0238) One hundred and four participants contributed data (Wolska 1995). The comparison with placebo found no statistically significant difference for platelet aggregation activating factor for total withdrawals. Data on withdrawals due to adverse events and withdrawals due to treatment failure were not reported.
35
Polymyxin B cream, 200,000 U/g Data were contributed by 30 participants (Stutz 1996). The comparison with placebo found no statistically signicant difference for polymyxin B cream for total withdrawals. Data on withdrawals due to adverse events and withdrawals due to treatment failure were not reported.
Analysis 7: vitamin D analogues vs. corticosteroid (potent) Seven of the eight vitamin D analogues that were compared with potent corticosteroids reported withdrawal data (withdrawal data on calcipotriol vs. desoxymetasone were not available) (see Analysis 7.6, Analysis 7.7 and Analysis 7.8). We pooled withdrawal data on these seven treatment comparison pairs using a random effects risk difference (RD) metric. Relative to potent corticosteroid, there was a statistically signicant difference in total withdrawals in favour of corticosteroids: RD: 0.02 (95% CI: 0.01 to 0.03; I: 0%). Rates of withdrawals due to adverse events were statistically signicantly different in favour of corticosteroids RD: 0.01 (95% CI: 0.00 to 0.02; I: 17.2%), but there was no signicant difference for withdrawals due to treatment failure: RD: 0.00 (95% CI: -0.01 to 0.01; I: 0%). Regarding individual vitamin D analogues, the only statistically signicant differences in withdrawals relative to corticosteroid were for the comparison of calcipotriol against betamethasone dipropionate (total withdrawals: RD: 0.03 (95% CI: 0.01 to 0.06; I: 0.0%); withdrawals due to adverse events: RD: 0.02 (95% CI: 0.00 to 0.04; I: NA)).
PTH (1-34) in Novasome A liposomal cream, BD Data were contributed by 30 participants (Holick 2003). The comparison with placebo found no statistically signicant difference for PTH (1-34) in Novasome A liposomal cream for total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Salicylic acid Withdrawal data on this product related to scalp psoriasis. Twenty participants contributed data (Elie 1983). The comparison with placebo found no statistically signicant difference for salicylic acid for withdrawals due to adverse events. Data on total withdrawals and withdrawals due to treatment failure were not reported.
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) We pooled withdrawal data on calcipotriol against clobetasol propionate using a random effects risk difference (RD) metric (see Analysis 8.6, Analysis 8.7 and Analysis 8.8). Relative to the very potent corticosteroid, we found no statistically signicant difference for calcipotriol on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Sirolimus (topical) The comparison reported no data on withdrawals associated with topical sirolimus relative to placebo.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid We pooled withdrawal data on Dovobet against betamethasone dipropionate using a random effects risk difference (RD) metric (see Analysis 9.6 and Analysis 9.7). Relative to the potent corticosteroid, we found no statistically signicant difference for calcipotriol on total withdrawals or withdrawals due to adverse events. No comparative data on withdrawals due to treatment failure were available.
Tacrolimus ointment This product was applied to facial psoriasis and psoriasis in the skin folds. One hundred and sixty-seven participants contributed data (Lebwohl 2004). Our review found no statistically signicant difference for tacrolimus ointment compared to placebo for withdrawals due to adverse events. However, there were statistically signicant differences in favour of tacrolimus for total withdrawals (RD: -0.17 (95% CI: -0.30 to -0.03; I: NA)) and for withdrawals due to treatment failure (RD: -0.11 (95% CI: -0.19 to -0.02; I: NA)).
Analysis 10: vitamin D analogues vs. dithranol Withdrawal data on three intervention-comparator pairs were available: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. We pooled these data using a random effects risk difference (RD) metric (see Analysis 10.6, Analysis 10.7 and Analysis 10.8). There was no statistically signicant difference for total withdrawals, either for individual intervention-comparator pairs or for the pooled effect (RD: -0.03 (95% CI: -0.06 to 0.00; I: 0%)). For the comparison of tacalcitol vs. dithranol,
36
Coal tar The comparison reported no data on withdrawals associated with coal tar relative to placebo.
there were no data available on withdrawals due to adverse events and withdrawals due to treatment failure. The comparison of calcipotriol vs. dithranol showed a statistically signicant difference in withdrawals due to adverse events in favour of calcipotriol: RD: -0.04 (95% CI: -0.06 to -0.01; I: 20.8%). However, there was no statistically signicant difference between calcitriol and dithranol. We found no statistically signicant difference in withdrawals due to treatment failure for either calcipotriol vs. dithranol or calcitriol vs. dithranol. Analysis 11: vitamin D analogues vs. coal tar No withdrawal data on calcipotriol against coal tar were available. For the comparison of calcipotriol and coal tar with white soft parafn, we pooled data using a random effects risk difference (RD) metric. We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure (see Analysis 11.6, Analysis 11.7 and Analysis 11.8). Analysis 12: Vitamin D analogue vs. vitamin D analogue Two of the three vitamin D analogues head-to-head comparisons reported withdrawal data (withdrawal data on calcipotriol vs. tacalcitol were not available). We pooled withdrawal data on calcipotriol vs. calcitriol and calcipotriol vs. maxacalcitol using a random effects risk difference (RD) metric (see Analysis 12.6, Analysis 12.7 and Analysis 12.8). We found no statistically significant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. However, there was substantial heterogeneity for the pooled data on withdrawals due to adverse events (RD: 0.03 (95% CI: -0.05 to 0.11; I: 58.0%)). Analysis 13: Vitamin D vs. vitamin D and corticosteroid To simplify the analysis, we summarised withdrawal data by grouping the rst ten intervention-comparator pairs in a single category: calcipotriol vs. calcipotriol and corticosteroid. The remaining comparison was tacalcitol vs. calcipotriol and corticosteroid. We pooled withdrawal data using a random effects risk difference (RD) metric (see Analysis 13.6, Analysis 13.7 and Analysis 13.8). In the comparison of calcipotriol against calcipotriol plus corticosteroid, total withdrawals were statistically signicantly different in favour of polytherapy: RD: 0.04 (95% CI: 0.02 to 0.05; I: 0.0%). Similarly, a signicant difference in favour of polytherapy was evident from the data on withdrawals due to adverse events: RD: 0.02 (95% CI: 0.01 to 0.03; I: 0.0%). However, we found no statistically signicant difference for withdrawals due to treatment failure. For the comparison of tacalcitol against calcipotriol plus corticosteroid, differences in total withdrawals and in withdrawals due to adverse events were not statistically signicant. However, when compared with tacalcitol there was a signicant difference in
favour of calcipotriol/ corticosteroid in the analysis of withdrawals due to treatment failure: RD: 0.05 (95% CI 0.02 to 0.08; I: NA)
Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid We pooled withdrawal data on calcipotriol vs. betamethasone dipropionate + salicylic acid using a random effects risk difference (RD) metric. We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure (see Analysis 14.6, Analysis 14.7 and Analysis 14.8).
Analysis 15: Calcipotriol vs. coal tar polytherapy We pooled withdrawal data on studies comparing calcipotriol with coal tar polytherapy using a random effects risk difference (RD) metric (see Analysis 15.6, Analysis 15.7 and Analysis 15.8). Our review found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Analysis 16: Head-to-head calcipotriol: Dosing We pooled withdrawal data on studies comparing different treatment frequencies of calcipotriol using a random effects risk difference (RD) metric. We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure (see Analysis 16.6, Analysis 16.7 and Analysis 16.8).
Analysis 17: Head-to-head: Occlusion There were no withdrawal data were for this comparison.
Analysis 18: vitamin D analogues vs. other treatment This comparison compared vitamin D analogue with seven other treatments. We assessed the results from the analyses of withdrawal data using a random effects risk difference (RD) metric and we report these separately (see Analysis 18.6, Analysis 18.7 and Analysis 18.8).
Calcipotriol vs. propylthiouracil cream We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Calcipotriol vs. tacrolimus ointment There were no withdrawal data reported for this comparison.
37
Calcipotriol vs. tazarotene We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
difference was only signicant in one of the two studies (Kaufmann 2002 (P)). We found no signicant difference in either of the pooled analyses of local adverse events or systemic adverse events data.
Analysis 2: Corticosteroid (potent) vs. placebo Calcipotriol vs. tazarotene gel plus mometasone furoate cream We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure. We pooled data on adverse events using a random effects risk difference metric (see Analysis 2.9 and Analysis 2.10). Among the eight potent corticosteroids evaluated against placebo, we found only one statistically signicantly difference. Once-daily betamethasone dipropionate was less likely than placebo to be associated with local adverse events: RD: -0.09 (95% CI: -0.14 to -0.03; I: NA). We found no signicant difference in either of the pooled analyses of local adverse events or systemic adverse events data.
Calcipotriol vs. vitamin B12 cream We found no statistically signicant difference on any of the withdrawal assessments: total withdrawals, withdrawals due to adverse events or withdrawals due to treatment failure.
Analysis 3: Corticosteroid (very potent) vs. placebo We pooled data on adverse events using a random effects risk difference metric (see Analysis 3.9 and Analysis 3.10). The comparison with placebo found no statistically signicant difference for any of the four very potent corticosteroids considered for either local adverse events or systemic adverse events.
Calcipotriol vs. Dovobet (four wks) then vitamin D (calcipotriol) weekdays/(Dovobet) weekends (four wks) We found a statistically signicant difference in favour of the maintenance therapy when we analysed total withdrawals: RD: 0.08 (95% CI: 0.03 to 0.13; I: NA). There were no reported data on withdrawals due to adverse events or due to treatment failure.
Analysis 4: Dithranol vs. placebo We pooled data on adverse events using a random effects risk difference metric (see Analysis 4.9 and Analysis 4.10). The comparison with placebo found no statistically signicant difference for pooled ndings on local adverse events or systemic adverse events. In one study, a signicant difference in favour of placebo was evident: RD: 0.40 (95% CI: 0.08 to 0.72; I: NA) (Volden 1992).
Tacalcitol vs.calcipotriol (four wks) then Dovobet (four wks) We found no statistically signicant difference in the assessment of total withdrawals or withdrawals due to adverse events. We found a statistically signicant difference in favour of Dovobet in the comparison of withdrawals due to treatment failure: RD: 0.05 (95% CI: 0.02 to 0.08; I: NA). (b) Adverse events (local and systemic)
Analysis 5: Tazarotene vs. placebo We pooled data on adverse events using a random effects risk difference metric (see Analysis 5.9 and Analysis 5.10). Tazarotene was statistically signicantly more likely than placebo to cause local adverse events: RD: 0.24 (95% CI: 0.02 to 0.46; I: NA). Our review found no signicant difference in the analysis of systemic adverse events.
(i) Findings from the main review
Analysis 1: vitamin D analogues vs. placebo We pooled data on adverse events using a random effects risk difference metric (see Analysis 1.9 and Analysis 1.10). Among the seven vitamin D analogues evaluated against placebo, we found only one statistically signicantly difference. Pooled data from two studies (Guenther 2002 (P); Kaufmann 2002 (P)) indicated that once-daily Dovobet was less likely than placebo to be associated with local adverse events: RD: -0.05 (95% CI: -0.10 to -0.01; I: 17.7%), although this may have been a chance nding as the
Analysis 6: Other treatment vs. placebo Our review reports ndings separately for 19 of the 22 comparisons considered (see Analysis 6.9 and Analysis 6.10). No data on adverse events were available for placebo comparisons involving polymyxin B cream; topical sirolimus or coal tar. Data on local adverse events were available for all 19 comparisons, but data on systemic adverse events were reported for just 9 comparisons. We assessed data on adverse events using a random effects risk difference metric. The review found only one statistically signicant
38
difference: tacrolimus was statistically signicantly less likely to be associated with local adverse events than placebo.
Fish oil plus occlusion The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with sh oil plus occlusion. Data on systemic adverse events were not reported.
Aloe vera extract The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with aloe vera extract. Data on systemic adverse events were not reported.
Hexauoro-1,25-dihydroxyvitamin D3 The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with hexauoro-1, 25-dihydroxyvitamin D3.
Anti IL-8 monoclonal antibody cream The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with anti IL-8 monoclonal antibody cream. Data on systemic adverse events were not reported.
Methotrexate gel The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with methotrexate gel.
Betamethasone-17,21-dipropionate plus salicylic acid The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with betamethasone-17,21-dipropionate plus salicylic acid. Data on systemic adverse events were not reported.
Mycophenolic acid ointment The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with mycophenolic acid ointment. Data on systemic adverse events were not reported.
Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid.
NG-monomethyl-L-arginine (L-NMMA) cream The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with NG-monomethyl-L-arginine (L-NMMA) cream.
Ciclopirox olamine shampoo This product is for scalp psoriasis. The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with ciclopirox olamine shampoo. Data on systemic adverse events were not reported. Ciclosporin solution in oil. This product is for nail psoriasis. The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with ciclosporin solution in oil.
Oleum horwathiensis The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with oleum horwathiensis.
Dead Sea salts emollient lotion The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with Dead Sea salts emollient lotion. Data on systemic adverse events were not reported.
Omega-3-polyunsaturated fatty acids ointment The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with omega3-polyunsaturated fatty acids ointment. Data on systemic adverse events were not reported.
39
Pimecrolimus cream, 1% BD The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with pimecrolimus cream. Data on systemic adverse events were not reported.
Coal tar Our review found no data on adverse events associated with coal tar.
Analysis 7: vitamin D analogues vs. corticosteroid (potent) Of the eight vitamin D analogues that were compared with potent corticosteroids, data on local adverse events were available for ve comparisons and data on systemic events were available for four comparisons (see Analysis 7.9 and Analysis 7.10). Data on local and systemic adverse events were not reported for calcipotriol vs. desoxymetasone; calcipotriol vs. diorasone diacetate; and calcitriol vs. betamethasone valerate. Systemic adverse events data were also unavailable for calcipotriol vs. uocinonide. We pooled data on adverse effects using a random effects risk difference metric. In the comparison of vitamin D analogues and potent corticosteroids, our review found two statistically signicantly differences in favour of potent corticosteroids. Local adverse events were signicantly more likely in the comparison of calcipotriol against either betamethasone dipropionate (RD: 0.07 (95% CI: 0.04 to 0.10; I: 0.0%) or betamethasone valerate (RD: 0.14 (95% CI: 0.03 to 0.25; I: 91.0%). The presence of substantial heterogeneity means that this estimate should be treated with caution. Our review found no other statistically signicant differences for local or systemic adverse events in this comparison.
Platelet aggregation activating factor (PAF)(Ro 24-0238) The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with platelet aggregation activating factor.
Polymyxin B cream, 200,000 U/g Our review found no data on local or systemic adverse events associated with polymyxin B cream.
PTH (1-34) in Novasome A liposomal cream, BD The comparison with placebo found no statistically signicant difference in the rate of either local or systemic adverse events associated with PTH (1-34) in Novasome A liposomal cream.
Analysis 8: vitamin D analogues vs. corticosteroid (very potent) Salicylic acid Adverse events data on this product related to scalp psoriasis. The comparison with placebo found no statistically signicant difference in the rate of local adverse events associated with salicylic acid. Data on systemic adverse events were not reported. We pooled withdrawal data on adverse effects using a random effects risk difference metric (see Analysis 8.9 and Analysis 8.10). Our review found no statistically signicantly difference between calcipotriol and clobetasol propionate.
Analysis 9: vitamin D analogues-potent steroid combination vs. potent corticosteroid We pooled data on adverse effects using a random effects risk difference metric (see Analysis 9.9 and Analysis 9.10). The pooled analysis found no statistically signicant difference between Dovobet and betamethasone dipropionate. This nding held for both once-daily (Kaufmann 2002 (H)) and twice-daily (Douglas 2002) dosing frequencies of Dovobet and betamethasone dipropionate.
Sirolimus (topical) Our review found no data on local or systemic adverse events associated with topical sirolimus.
Tacrolimus ointment This product was applied to facial and intertriginous psoriasis. The comparison with placebo found a statistically signicant difference in favour tacrolimus ointment for local adverse events: RD: -0.17 (95% CI: -0.30 to -0.03; I: NA). The analysis of withdrawals due to adverse events and of systemic adverse events found no statistically signicant difference.
Analysis 10: vitamin D analogues vs. dithranol Adverse events data on three intervention-comparator pairs were available: calcipotriol vs. dithranol; tacalcitol vs. dithranol; and calcitriol vs. dithranol. We pooled these data using a random effects risk difference metric (see Analysis 10.9 and Analysis 10.10). Overall, vitamin D was statistically signicantly less likely to cause local adverse events: RD: -0.28 (95% CI: -0.45 to -0.11; I: 92.7%),
40
although substantial heterogeneity was evident. This nding also held for each of the three intervention-comparator pairs, with the effect size ranging from -0.20 (calcipotriol vs. dithranol) to -0.67 (calcitriol vs. dithranol). However, we found no statistically signicant difference for systemic adverse events.
Analysis 15: Calcipotriol vs. coal tar polytherapy We pooled adverse events data on studies comparing calcipotriol with coal tar polytherapy using a random effects risk difference (RD) metric (see Analysis 15.9 and Analysis 15.10). Our review found no statistically signicantly difference in the rates of local or systemic adverse events.
Analysis 11: vitamin D analogues vs. coal tar We pooled data on adverse effects using a random effects risk difference metric (see Analysis 11.9 and Analysis 11.10). Data on local adverse events were not reported. Our review found no statistically signicantly difference in the rates of systemic adverse events between calcipotriol and coal tar. Analysis 16: Head-to-head calcipotriol: Dosing We pooled data on adverse effects using a random effects risk difference (RD) metric (see Analysis 16.9 and Analysis 16.10). Our review found no statistically signicant difference in the rates of local or systemic adverse events.
Analysis 12: vitamin D analogue vs. vitamin D analogue Local adverse events data were reported on two of vitamin D analogues head-to-head comparisons (see Analysis 12.9 and Analysis 12.10). Systemic adverse events data were not available for the comparison of calcipotriol and calcitriol. We pooled data on adverse effects using a random effects risk difference metric. Overall, our review found no statistically signicant difference on either local or systemic adverse events comparing pooled vitamin D analogues head-to-head. However, in the local adverse events comparison of calcipotriol against calcitriol, our review found a statistically signicant difference in favour of calcitriol: RD: 0.09 (95% CI: 0.02 to 0.17; I: NA). Analysis 17: Head-to-head: Occlusion No data on local adverse events were available for analysis. We pooled data on systemic adverse events using a random effects risk difference (RD) metric (see Analysis 17.10). Our review found no statistically signicantly difference between calcipotriol with and without occlusion.
Analysis 18: vitamin D analogues vs. other treatment A vitamin D analogue was compared with seven other treatments (see Analysis 18.9 and Analysis 18.10). We assessed results from the analyses of adverse events data using a random effects risk difference metric and report these separately.
Analysis 13: Vitamin D vs. vitamin D and corticosteroid To simplify the comparison, we summarised adverse events data by grouping the rst ten intervention-comparator pairs in a single category: calcipotriol vs. calcipotriol and corticosteroid. The remaining comparison was tacalcitol vs. calcipotriol and corticosteroid. We pooled data on adverse effects using a random effects risk difference (RD) metric (see Analysis 13.9 and Analysis 13.10). In the local adverse events comparison of vitamin D against vitamin D plus corticosteroid, our review found a statistically significantly difference in favour of polytherapy: RD: 0.07 (95% CI: 0.05 to 0.09; I: 18.3%). This nding held for both interventioncomparator pairs. Our review found no statistically signicantly difference in the rates of systemic adverse events in this analysis.
Calcipotriol vs. propylthiouracil cream Our review found no statistically signicant difference for local or systemic adverse events.
Calcipotriol vs. tacrolimus ointment Adverse events data for this analysis were not reported.
Analysis 14: Calcipotriol vs. corticosteroid and salicylic acid We pooled data on adverse effects using a random effects risk difference (RD) metric (see Analysis 14.9 and Analysis 14.10). In the local adverse events comparison of calcipotriol against corticosteroid plus salicylic, our review found a statistically signicantly difference in favour of the corticosteroid/salicylic acid: RD: 0.07 (95% CI: 0.00 to 0.14; I: 11.6%). Our review found no statistically signicantly difference in the rates of systemic adverse events.
Calcipotriol vs. tazarotene Our review found no statistically signicant difference for local or systemic adverse events.
Calcipotriol vs. tazarotene gel plus mometasone furoate cream Adverse events data for this analysis were not reported.
41
Calcipotriol vs. vitamin B12 cream Our review found no statistically signicant difference in the rates of local adverse events. Data on systemic adverse events were not reported.
Calcipotriol vs. Dovobet (four wks) then vitamin D (calcipotriol) weekdays/(Dovobet) weekends (four wks) Our review found a statistically signicant difference in favour of the maintenance therapy when data on local adverse events were analysed: RD: 0.11 (95% CI: 0.05 to 0.17; I: NA). Data on systemic adverse events were not reported.
Tacalcitol vs. calcipotriol (four wks) then Dovobet (four wks) Our review found a statistically signicant difference in favour of the maintenance therapy when data on local adverse events were analysed: RD: 0.06 (95% CI: 0.01 to 0.11; I: NA). Data on systemic adverse events were not reported.
(ii) Findings from the separate search for additional studies of adverse events
In addition to ndings on adverse events from the main review, we undertook a separate search for additional studies. The search identied six literature reviews and 36 potentially relevant records. Twenty-one studies (reported in 23 references) met the inclusion criteria and we excluded13 studies from the review (Aste 2004; Bos 2002; Floden 1975; Franssen 1999; Kang 1998; Lebwohl 1996; Park 2002; Senter 1983; Singh 2000; Stevanovic 1977; Traulsen 2003; Uhoda 2003; Vissers 2004). Table 24 details the characteristics and key ndings of the included studies and Table 25 lists the excluded studies. The study by Gerritsen 2001 was also reported by Langner 1996 and van de Kerkhof 1996c. One paper reported two studies (Berth-Jones 1993) which were analysed separately and Berth Jones 1992c reported additional details for one of these studies. The study by van de Kerkhof 2002c reported a two-phase open study of tacalcitol, where responders to part 1 were eligible for part 2. Full results for part 2 were not reported separately (e.g. incidence of local adverse events was reported only for all trial participants). The study by Lambert 2002 appeared very similar to the second phase of the study reported by van de Kerkhof 2002c, but as there was no explicit evidence of an association it was analysed as a separate trial. Of the 21 included adverse events studies, 14 were uncontrolled (Barnes 2000; Berth Jones 1992c; Berth-Jones 1993; Bleiker 1998; Cullen 1996; Gerritsen 2001; Kragballe 1991b; Lambert 2002; Langner 1996; Miyachi 2002; Poyner 1993; Ramsay 1994; van de Kerkhof 1997b; van de Kerkhof 2002c; Vazquez-Lopez 2004), six were randomised trials (Corbett 1976; Guzzo 1996; Katz 1987b; Katz 1989; Lebwohl 1998b; Lebwohl 2001), one was a
retrospective controlled study (Heng 1990) and one reported a control group of persons using treatment other than calcipotriol (Berth-Jones 1993). None of the six RCTs was included in the main review. Five RCTs did not meet the inclusion criteria for the main review because they did not address comparisons of interest (Corbett 1976; Katz 1987b; Katz 1989; Lebwohl 1998b), or did not assess effectiveness (Guzzo 1996). One RCT was excluded from the main review: although the study met the inclusion criteria, it could contribute no data to the analysis because numbers of participants in each arm of the trial were not reported (Lebwohl 2001). In all six RCTs, the adequacy of concealment of treatment allocation was unclear, the method of randomisation was unclear and all were double-blind (participant/investigator) trials. Four of the six trials reported baseline comparability, with one study demonstrating between-group comparability in both clinical and demographic characteristics (Katz 1989), two reporting differences in baseline severity (Guzzo 1996; Lebwohl 1998b) and one reporting differences in demographics (Katz 1987b). Three of the six RCTs were placebo-controlled and three were head-to head studies. Of the seven controlled studies, two were within-patient designs (Corbett 1976; Katz 1989) and ve were between-patient (parallel group) designs (Katz 1987b; Lebwohl 1998b; Guzzo 1996; Lebwohl 2001; Heng 1990).Trials ranged in size from 10 to almost 400 participants. Treatment duration ranged from 2 weeks to 18 months. Loss to follow up averaged 14% (range: 0% to 63%) and was higher for trials with longer follow-up periods. The mean age of participants was 45 (range: 15 to 85). Participants were more likely to be male (mean: 58%, range: 40 to 82%). In ten studies, the baseline severity of participants was unclear. Remaining studies recruited participants with mild to moderate disease (N = 2), mild to severe disease (N = 3), moderate to severe disease (N = 4) and severe disease (N = 2). Study treatments included vitamin D products (16/21), topical corticosteroids (7/21) and tazarotene (1/21). Some comprised of combination regimens such as vitamin D and corticosteroid (Lebwohl 1998b; Vazquez-Lopez 2004) or tazarotene and corticosteroid (Lebwohl 2001). No study of coal tar or dithranol met the inclusion criteria for the review. Fifteen of the studies assessed local adverse events, 15 assessed systemic effects and 9 studies assessed both. Although three RCTs reported some data on adverse events (Katz 1987b; Lebwohl 2001; Lebwohl 1998b), these were neither suitable nor adequate for pooling.
Vitamin D products (N=16) Eleven studies evaluated either local (N = 7) or systemic (N = 8) adverse effects associated with calcipotriol. The rate of withdrawals due to local adverse events ranged from 4 to 14% and the rate of adverse events ranged between 20 and 41%; larger trials reported higher rates (weighted mean: 36%). In the 52-week trial by Barnes 2000, facial irritation affected 30% of participants in the early stages of the trial, but the incidence declined over time. The incidence of systemic effects was less common: 5/8 studies found no
42
signicant effects. Bleiker 1998s study of inpatients with severe disease found 5/28 developed hypercalcaemia after receiving dose greater than 5 g/kg. The study by Berth-Jones 1993, in which 10 trial participants received a weekly dose of 100 g of calcipotriol for 4 weeks, found that urinary calcium increased signicantly from baseline levels. Four studies evaluated both local and systemic adverse effects associated with tacalcitol. The rate of withdrawals due to local adverse events ranged from 0 to 6% and the rate of adverse events ranged between 10 and 21%. Three studies found no systemic effects. The study by van de Kerkhof 2002c found that over half of those with BSA 10 to 20% exceeded recommended daily dose of 5 g (up to 13 g daily), but there was no effect on calcium homeostasis. Systemic effects were identied in over half enrolled participants in the trial by Miyachi 2002 but only 6/155 events were considered to be treatment-related in this uncontrolled study. One study looked at adverse events associated with calcitriol in 257 participants with moderate to severe disease (Gerritsen 2001). Three per cent of participants withdrew due to adverse events and 15% were affected by local adverse events. The withdrawal rate due to systemic effects was low (0.4%) but four cases of hypercalcaemia were reported (N = 253). Mean daily use of calcitriol in this trial was 6 g (range: 1 to 24 g).
method was not reported. The study of tazarotene /steroid against tazarotene/ placebo found no difference in local adverse effects (Lebwohl 2001). Two studies examined systemic effects associated with corticosteroids. The study by Corbett 1976 compared betamethasone valerate with clobetasol propionate. Quantities used by study participants were small (mean: 7 g/wk) and no pituitaryadrenal suppression was observed. The trial by Katz 1987b compared two superpotent corticosteroids and identied temporary and reversible adrenal suppression in 20% (8/40) study participants. No study reported relevant data on tachyphylaxis. Tazarotene (N=1) The study by Lebwohl 2001compared three types of maintenance therapy: tazarotene plus steroid, tazarotene plus placebo and placebo alone. In this 6-month trial there were no withdrawals due to adverse events, but adverse events were experienced by 24% of participants in the tazarotene/steroid group, 29% of participants in the tazarotene/placebo group. There were no adverse events in the placebo group and systemic effects were not assessed.
(c) Quality of life measures
Corticosteroids (N = 7) Two adverse events studies compared steroids with no steroids (Heng 1990;Katz 1989), three studies compared steroids head-tohead (Corbett 1976;Katz 1987b; Katz 1989) and one evaluated combination maintenance therapy with tazarotene and steroid against tazarotene with placebo (Lebwohl 2001). Two studies looked at combination maintenance therapy with calcipotriol: the study by Lebwohl 1998b compared steroid plus vitamin D against steroid plus placebo and Vazquez-Lopez 2004 reported an uncontrolled study of steroid plus vitamin D.The retrospective study by Heng 1990 compared 13 participants who had used topical corticosteroids for between 6 months and 12 years with a no steroid group: these 15 individuals had previously used tar, UVB or no therapy. Light microscopy revealed no between group differences. However, electron microscopy revealed multi-layered, fragmented and disorganised basal laminae (the lining of the outer surface of the cell membrane) in the steroid group; this appeared to be correlated with duration of treatment. Fragmentation was not observed in the control group. The 4-week study by Katz 1989 identied pre-atrophy in 20% of involved plaques, and the 34-week study by Vazquez-Lopez 2004 found that topical steroids were associated with the appearance of clinically unapparent but dermoscopically apparent linear telangiectasias in 5/20 participants, of whom 4 had overused topical steroid cream. When steroids were discontinued in these participants, there was complete resolution within 2 months. No cutaneous atrophy was observed in participants receiving maintenance therapy with either calcipotriol / steroid or placebo/steroid (Lebwohl 1998b), but the assessment
Quality of life (QOL) was formally assessed in four of the 133 studies included in the main review, of which 3 were head-tohead trials (Guenther 2002 (H); Guenther 2002 (P); Hutchinson 2000; Wall 1998). In the two trials by Guenther (2002), quality of life was measured using the Psoriasis Disability Index (PDI) and the EuroQOL (EQ-5D and EQ-VAS) and reported in a separate publication ( van de Kerkhof, 2004). Both Hutchinson 2000 and Wall 1998 also assessed quality of life using the Psoriasis Disability Index; Wall 1998 also used the Sickness Impact Prole (SIP). Although all four studies used the PDI to measure quality of life, data were not reported in sufcient detail to allow pooling and so ndings are reported narratively.Whereas the trial by Wall 1998 included participants with mild to moderate disease, the other three trials included participants with at least moderately severe disease. The number of participants ranged from 114 (Hutchinson 2000) to 828 (Guenther 2002 (P)) although PDI scores were obtained for only 51% of participants in this trial (van de Kerkhof, 2004). Psoriasis Disability Index (PDI) (N = 4) In all four trials reporting this measure, there was an improvement in mean quality of life scores for participants in every group. The trial by Guenther 2002 found the greatest improvement (reduction in PDI from baseline i.e. improvement in QOL) for twice daily Dovobet (50%). Corresponding gures were: once daily Dovobet (plus placebo): 41%; calcipotriol twice daily: 31% and placebo twice daily: 9%. In terms of absolute scores, the group using twice daily Dovobet had the best (lowest) quality of life score, followed by the once-daily Dovobet group, calcipotriol group and placebo group. Relative to baseline, improvements in mean quality of life
43
scores were statistically signicant in all treatment groups, but the statistical signicance of between-group differences was not reported. In the study by Hutchinson 2000, quality of life improved from baseline signicantly more in the group treated with calcitriol relative to the dithranol group. The comparison of dithranol and calcipotriol by Wall 1998 found that the magnitude of the difference was greater in the calcipotriol group, but the difference was not statistically signicant at the 5% level. EuroQOL (EQ-5D and EQ-VAS) (N = 1) The EQ5D is a generic quality of life measure. van de Kerkhof, 2004 reported quality of life data from the trial by Guenther 2002. The EQ5D scores were presented in a non-standard method, making their interpretation problematic. EQ-VAS (scored from 1 to 100) supported ndings from the PDI assessments, with all groups improving quality of life scores relative to baseline. However, the EQ-VAS score for the once-daily Dovobet (plus placebo) group was higher (with a better quality of life) than the corresponding score in the twice daily Dovobet group. Relative to baseline, improvements in mean quality of life scores were statistically signicant in all treatment groups, but the statistical signicance of between-group differences was not reported. Sickness Impact Prole (SIP) (N=1) The SIP is a generic quality of life measure. Wall 1998 assessed participants using the SIP, which has a maximum score of 136. As with the PDI, the SIP found a statistically signicant improvement from baseline in both groups, but the between-group difference was not statistically signicant.
(d) Economic outcomes
informative to clinical decision makers. The relative short-term clinical performance of topical anti-psoriatic treatments can be set against their reimbursed costs. While it is accepted that long-term sequelae in participants not responding to treatment may be very important when considering overall costs and benets, there are no good comparative data on these costs with which to distinguish between treatments.
(e) Concordance or compliance with treatment
A number of studies have looked at economic aspects of topical treatment for psoriasis. These include cost-of-illness studies (Feldman 1997; Jenner 2002; Poyner 1999), quality-of-life studies (Leu 1985; Lundberg 1999; Ortonne 2000; Schiffner 2003; Zachariae 2002; Zug 1995), methodological issues (Lambert 1996; Lambert 1999), willingness to pay analyses (Lundberg 1999; Poyner 2000; Schiffner 2003), cost analysis (Feldman 2000) and cost-effectiveness analyses (Ashcroft 2000; de Tiedra 1997; Harrington 1995; Kse 1997; Marchetti 1998; Oh 1997; Owen 1993; Parodi 1991; Schwicker 1992; Sorensen 2002; Stern 1988). These analyses involve a range of modelling approaches and assumptions and have not been formally reviewed here. Our review reveals no substantial variations in tolerability or effectiveness for most treatment comparisons, and no trials provide robust resource data on the consequences of managing treatment failure. Consequently, any economic models extrapolating beyond the duration of the trials may be largely speculative and uninformative. In the light of available data, a cost and consequences approach, in which costs and outcomes are reported separately, may be most
The separate search for studies of compliance identied 246 potentially relevant studies for screening. Of these, 18 papers were retrieved and 12 papers reporting on 11 studies were included in the review (see Table 26) (Balkrishnan 2003; Carroll 2004a; Carroll 2004b; Feldman 2007; Ferrandiz 1998; Fouere 2005; Gokdemir 2008; Richards 1999; van de Kerkhof 1998c; van de Kerkhof 2000; van de Kerkhof 2001; Zaghloul 2004). Some studies were pilots (e.g. Balkrishnan 2003; van de Kerkhof 1998c) for other studies (i.e. Carroll 2004a; van de Kerkhof 2000). Studies that did not meet the inclusion criteria are listed in Table 27 (Atkinson 2004; Chu 2000; Gupta 2007; Lee 2006; Osborne 2002; Richards 2006; Szeimies 2004). Three reviews were identied and bibliographies were checked for further potentially relevant studies (Gupta 2007; Lee 2006; Richards 2006). Of the 11 studies included in the review, 2 were randomised controlled trials (Carroll 2004a; Ferrandiz 1998) and 4 were questionnaire surveys Fouere 2005; Richards 1999; van de Kerkhof 1998; van de Kerkhof 2000). The remaining ve studies were prospective experiments, of which one included a control group (van de Kerkhof 2001). The number of participants included in the compliance studies ranged from 10 to 1281 and the study duration ranged from 1 to 16 weeks. In total, 5541 participants were enrolled in the 11 studies, of which 39% were male and the mean age was 47.0 (range: 4 to 91). Study size ranged from 10 to 1281 participants, with the questionnaire surveys reporting the largest sample sizes. Studies covered four main issues. First, some reported methodological issues on the measurement of compliance (Balkrishnan 2003; Carroll 2004a; Fouere 2005; Zaghloul 2004). Second, some studies reported compliance rates (Balkrishnan 2003; Carroll 2004a; Fouere 2005; Richards 1999; van de Kerkhof 2000; van de Kerkhof 2001; Zaghloul 2004). Third, reasons for non-compliance were considered by seven studies (Carroll 2004a; Gokdemir 2008; Fouere 2005; Richards 1999; van de Kerkhof 1998c; van de Kerkhof 2000; Zaghloul 2004). Fourth, three studies assessed interventions to improve compliance (Feldman 2007; Ferrandiz 1998; van de Kerkhof 2001).
Methodological issues to do with compliance measurement and compliance rates Some studies used self-reported compliance rates (Gokdemir 2008; Richards 1999; van de Kerkhof 2000; van de Kerkhof
44
2001; Zaghloul 2004). In these studies, which included short-term prospective trials and cross-sectional questionnaire surveys, rates varied between 61 and 72%. However, other studies adopted more objective assessment methods. The study by Fouere used a semistructured participant questionnaire: the PMAQ-3w scale (patient medication adherence questionnaire) asked about strict adherence to prescribed regimen over the previous three days and previous weekend. Using this method, just 27% of participants were deemed to be compliant (Fouere 2005). Some studies adopted a single-blind approach to assess electronic bottle caps (i.e. participants were unaware that bottles were tted with electronic measuring devices) (Balkrishnan 2003; Carroll 2004a; Feldman 2007). Known as a MEMS cap, the medication bottle cap was tted with microprocessor to record time / date of every opening of the bottle. When compared with participant logs, electronic methods suggested that compliance was considerably lower than rates reported by participants. For example, Balkrishnans 1-week pilot study of 10 participants found that the compliance rate was 67% by electronic assessment compared with a self-reported rate of 92%. Carroll and colleagues took this pilot study forward using an 8-week trial of 30 participants (Carroll 2004a). Compliance fell over time and averaged 55% over the study period when assessed using the MEMS cap. Twice-daily dosing was achieved on 39% of the treatment days. Reasons for non-compliance Reasons for non-compliance comprised therapy characteristics (real or perceived); participants clinical characteristics; and participants demographic characteristics.Regarding therapy characteristics, efcacy (Fouere 2005; van de Kerkhof 1998c; van de Kerkhof 2000), side-effects (Fouere 2005; Richards 1999; Zaghloul 2004), time for application (Fouere 2005; Gokdemir 2008; van de Kerkhof 2000) and messiness (Fouere 2005; Richards 1999; van de Kerkhof 1998c) were identied as inuences on compliance by the included studies. Compliance was higher for topical therapy compared with systemic treatment (Zaghloul 2004), but compliance rates also varied by type of topical treatment (Fouere 2005). Disease severity was inversely related to compliance (Richards 1999; Carroll 2004a), although the direction of causality is unclear. Higher compliance rates were variously associated with female gender (Carroll 2004a; Zaghloul 2004), older age (Carroll 2004a; Richards 1999}, higher educational achievement (Gokdemir 2008) and older age of disease onset (Richards 1999), but ndings on marital status were mixed (Gokdemir 2008; Zaghloul 2004). Methods to improve compliance Ofce visits to clinicians were found to temporarily increase compliance rates (Carroll 2004a; Feldman 2007). An educational programme designed to improve compliance had no impact on the effectiveness of treatment (Ferrandiz 1998). Van de Kerkhof s study
comparing ointment /cream regimen with ointment-only treatment found no clear impact, with 51% of participants reporting better compliance with the cream/ointment option (van de Kerkhof 2001).
DISCUSSION
Summary of main results
Effectiveness This review focuses on evidence from 131 studies that included 21,448 participants. Six placebo-controlled comparisons were evaluated. Most treatments were statistically signicantly more effective than placebo, with the pooled effect on a 6-point IAGI scale ranging from 1.0 (tazarotene) to 1.4 (very potent corticosteroid). The pooled effect on a 6-point improvement (IAGI) scale indicated similar improvements for vitamin D analogues (1.3 points), corticosteroids (1.0 points), dithranol (1.1. points) and tazarotene (1.0 points). Results for the individual vitamin D analogues varied widely, ranging from 0.9 points (tacalcitol) to 2.1 (Dovobet BD). Amongst less-frequently researched treatments compared against placebo, 11 treatments were found to have statistically signicant benecial effects. For these treatments, the effect on a 6-point IAGI scale ranged from 0.6 (anti IL-8 monoclonal antibody cream) to 2.5 (PTH (1-34) in Novasome cream). Betamethasone-17,21dipropionate plus salicylic acid achieved a 1.8 improvement on the 6-point IAGI scale. One small within-patient study found that tar was no more effective than placebo (Kanzler 1993). Twelve head-to-head comparisons were evaluated. When vitamin D was compared against potent corticosteroids or very potent corticosteroids, neither analysis found a statistically signicant difference in effect. Relative to vitamin D, combined treatment with vitamin D and corticosteroid was more effective (0.48 point improvement on a 6-point IAGI scale). This combined regimen was also more effective than corticosteroid alone, and offered an improvement of 0.55 points. Coal tar, either alone or as polytherapy, was statistically signicantly less effective than vitamin D, with the difference on a 6-point IAGI of 1.2 in favour of vitamin D. Occlusion and twice daily dosing signicantly enhanced the effectiveness of calcipotriol, with improvements on the 6-point IAGI of 0.8 and 0.2 points respectively. No head-to-head trials of vitamin D against tazarotene were identied. Adverse effects Randomised evidence found that vitamin D was not associated with a higher incidence of local adverse effects, such as cutaneous irritation, when compared with placebo (13% of participants for
45
both groups). However, vitamin D was signicantly more likely than potent corticosteroids to cause local adverse effects and participants were more likely to withdraw for this reason. One possible interpretation of this apparent anomaly is that the corticosteroids exerted an anti-inammatory effect which was more noticeable to trial participants using vitamin D than to participants in placebocontrolled trials. Studies of longer-term adverse events found that up to 40% of those using vitamin D analogues experienced cutaneous effects and that up to 14% of participants stopped using vitamin D analogues for this reason. There was some evidence to suggest that using vitamin D analogues at high doses could cause systemic adverse effects. Randomised evidence found that topical corticosteroids were as well tolerated as placebo and associated with a lower incidence of cutaneous adverse effects than vitamin D analogues. Two of the major cutaneous adverse effects of topical corticosteroids are dermal and epidermal atrophy (Hengge 2006). Only 10 of the 131 RCTs explicitly assessed cutaneous atrophy, and in these the duration of the trials, skin sites assessed and methods employed reduced the chance of detection. Methods used to assess atrophy were not reported in 5/10 trials, undertaken by physicians (5/10) or self-reported (3/10). Where physician assessments were conducted, the methods used were not stated (for example whether microscopy was used). Two trials reported cases of atrophy (Kragballe 2004; Guenther 2002 (H)). Some studies of longer-term use of topical corticosteroids revealed atrophy and damage to basal laminae, the extent of which appeared to be correlated with dosage and duration of use. This nding is supported by research of very potent steroids on the skin of normal volunteers (Kao 2003). Longerterm use with topical retinoids caused cutaneous effects in around 30% of participants, but systemic effects were not assessed.
ference in outcomes, a nding which contrasts with evidence on an educational programme for atopic dermatitis (Cork 2003). However, whereas the programme in the Ferrandiz 1998 study provided education about the disease, the study by Cork involved specialist nurses teaching methods for applying topical treatments. Therefore, the ndings from Ferrandiz 1998 should be generalised with caution.
Sensitivity analysis In ve comparisons, we used sensitivity analysis to explore whether within-patient vs. between-patient study designs were associated with different effect sizes. When comparing within-patient and between-patient study designs, our review found no statistically signicant difference in treatment effect size. If within-patient studies featured some correlation, due to systemic effects or cross contamination, then one would expect systematically smaller effect sizes from within-patient studies. If there is there is no correlation, then one would expect the variance to be smaller (as other sources of between-patient variation have been removed) but the effect size to be similar. We found no evidence to support a correlation for within-patient studies, with the sign of the difference in treatment effect for three of the ve comparisons favouring within-patient designs. There was little difference in the placebo-controlled studies of vitamin D products: on average, within-patient studies identied a slightly greater effect than between-patient studies (mean difference: 0.04 points on a 6-point IAGI scale). For placebo-controlled potent corticosteroids, there was a more pronounced difference in favour of within-patient studies (mean difference: 0.44 points on a 6-point IAGI scale). In the case of very potent corticosteroids, the mean effect relative to placebo was larger in the between-patient studies (mean difference: 0.09 points on a 6-point IAGI scale) and the analysis of vitamin D against potent corticosteroid was similar in this respect (a small positive difference in favour of between-patient studies). The analysis of vitamin D plus corticosteroid against vitamin D alone found a larger difference in the within-patient studies (mean difference: 0.22 points on a 6-point IAGI scale). In most cases, the statistical signicance of the result was the same whether between-patient or within-patient studies were analysed. However, in the analysis of vitamin D plus corticosteroid against vitamin D alone, the difference was signicant in the ten betweenpatient studies but not signicant for within-patient studies (N = 2). Given the small number of within-patient studies, this nding should be interpreted with caution. In four comparisons, we used sensitivity analysis to explore whether effect sizes differed between trials of scalp psoriasis and non-scalp psoriasis (no trials of scalp psoriasis were included in the analysis of vitamin D plus corticosteroid against vitamin D alone). Compared with applications to the body, the analyses of placebo-controlled trials suggested that both potent and very potent corticosteroids appeared to have a greater effect when applied
46
Compliance Thirteen of the 131 RCTs assessed compliance and 8 trials reported ndings. Trials used various methods such as self-report by participants, medication weight and treatment completion. Most studies that assessed compliance found it to be sub-optimal. However, Gupta has argued that the relevant notion is concordance rather than compliance (Gupta 2007). Whereas compliance implies that people adhere to clinician prescribed treatment, concordance involves a negotiated doctor-patient agreement on treatment regimen. Van de Kerkhof s survey of over 800 European people with psoriasis found that some chose not to comply, preferring to apply the minimum dose needed to achieve the effect they wanted (van de Kerkhof 2000). If prescribed regimens reected the wishes of the person with psoriasis, compliance rates might be expected to rise. Nonetheless, poor adherence to treatment regimens is likely to impair the effectiveness of treatment. . The review identied one study that used an educational programme to improve compliance rates in people with psoriasis (Ferrandiz 1998). This study found no statistically signicant dif-
to the scalp. In the analysis of vitamin D against corticosteroid, there was a statistically signicant difference in favour of corticosteroids applied to the scalp. In the analysis of these treatments applied only to the body, the difference between the effects of the two treatments was not statistically signicant. Placebo-controlled evidence on vitamin D for scalp psoriasis was limited to one small trial, so robust conclusions cannot be drawn.
Potential biases in the review process

There are a number of limitations to this review. First, data were extracted by one author and checked by a second. Ideally, two authors should extract data independently (NHSCRD 2001). However, this approach was not feasible for this review because of funding constraints. Second, requests for unpublished data from triallists and sponsors were of variable success; requests were more likely to be successful when made for more recently published studies and / or products still on patent.
Quality of the evidence

All included trials were randomised, but only 32 studies clearly reported the method used to randomise participants. Just 12 trials adequately concealed treatment allocation, but most (105/133) masked participants to treatment allocation. Of the 133 studies assessed, 121 reported loss to follow up and 84 demonstrated that groups were comparable at baseline. Based on the 62/133 studies that reported assessable data on baseline severity, it was clear that a wide range of severity was included within and between trials. If the PASI is unreliable for mild-to-moderate disease (PASI scores less than 10)(Brownell 2007), it is possible that some trials may have contributed unreliable PASI data to this review. Trials varied in their treatment duration and in their outcome measures (see Included studies section for details). One reason for the variation in trial treatment duration is that the time taken for an intervention to be effective differs between treatments.The analyses and Forest plots do not provide information on treatment duration, but this is an important consideration for clinical decisions. Trials also used different outcome measures; for example, only 71 studies reported data on the IAGI and 46 studies reported PASI data. In order to maximise the number of studies contributing data for a particular treatment comparison, we used a combined endpoint that incorporated different outcome measures.This approach is not ideal; although all outcome measures essentially assess redness, thickness and scaling (and sometimes area of psoriatic involvement), they differ in their construct. Therefore, the composite endpoints should be seen as indicative rather than denitive. Medical text books commonly document the risk of skin atrophy and tachyphylaxis as problems associated with topical corticosteroids (Bos 2008). Randomised evidence reported in this review suggests that maintenance regimens using intermittent dosing are safe and effective, and no RCT included in the review detected a statistically signicant difference in systemic effects. We undertook a separate search for longer-term trials of adverse events that identied seven relevant studies of corticosteroids. Studies were heterogeneous in terms of design, assessment methods, comparators considered and doses used, so data could not be pooled. Three studies found evidence of basal damage and atrophy. We identied no studies reporting adequate data on tachyphylaxis despite including this term in our searches. All included studies assessed relatively few participants (range: 14 to 50) and were variable in their follow-up duration (range: 3 weeks to over 6 months).
Agreements and disagreements with other studies or reviews

A systematic review by Ashcroft and colleagues focused on headto-head trials of one vitamin D analogue, calcipotriol (Ashcroft 2000a). Based on data from 37 studies with over 6000 participants, the review found that calcipotriol was at least as effective as potent topical corticosteroids and more effective than calcitriol, tacalcitol, coal tar, and short contact dithranol. Our review generally supports these ndings. However, we found no significant difference for the comparison of calcipotriol and calcitriol (SMD: -0.16; 95% condence interval -1.83 to 1.51). Although we also found that short-contact dithranol is less effective than calcipotriol, physicians and those with psoriasis may be interested to know that inpatient treatment with dithranol appears more effective than calcipotriol (Monastirli 2000). Our review also supported ndings from the review by Ashcroft 2000a that although calcipotriol caused signicantly more skin irritation than potent topical corticosteroids, skin irritation rarely led to withdrawal of calcipotriol treatment. The review by A 2005 concluded that combined treatment with steroids and vitamin D analogues or topical retinoids appeared the most promising current treatment on account of its superior efcacy and favourable side-effects prole. However, longer-term adverse effects were not addressed by this review. In contrast, the review by Bruner 2003a focused on adverse effects. This review supported our ndings that there is little robust evidence on longerterm adverse effects and therefore concluded that, since clearance is not a realistic expectation, reasonable goals are needed to avoid increasing the risk of cutaneous and systemic side effects through over use.
AUTHORS CONCLUSIONS Implications for practice

Evidence from large numbers of trials indicates that most of the topical treatments tested in the trials reviewed here alleviate the symptoms of psoriasis. However, it was not possible to assess the performance of treatments at different levels of severity of psoriasis.
47
The evidence suggests that vitamin D products are more effective than emollient alone. Potent and very potent corticosteroids are also effective and very potent corticosteroids are more effective than either potent corticosteroids or vitamin D products. The effectiveness of dithranol and tazarotene appears to be similar to that of vitamin D products. Although vitamin D and corticosteroids are equally effective for treating psoriasis of the body, corticosteroids appear to be more effective than vitamin D for treating psoriasis of the scalp. Combined treatment of vitamin D with corticosteroid is more effective than either vitamin D alone or corticosteroid alone. Vitamin D is more effective than coal tar, but ndings on the relative effectiveness of vitamin D and dithranol were mixed. Occlusion enhances the effectiveness of vitamin D, as does twice-daily rather than once-daily application. Compared with vitamin D alone, combined therapy that uses two products separately (vitamin D in the morning and corticosteroid at night) can achieve similar effects, and be as well tolerated, as using a combined product. However, some corticosteroids seem to perform better than others when used separately (see Analysis 13.5 and Analysis 13.9) and treatment performance may also be affected by disease severity, though poor reporting of baseline severity in trials means that this cannot be conrmed. Concordance may also be enhanced when using a combined product, and there is evidence to suggest that compliance is higher when application time is shorter. Potent corticosteroids are less likely than vitamin D to cause local adverse events and treatment with corticosteroids is less likely to result in discontinued use because of these adverse events. Tazarotene is more likely than emollient to cause local adverse events. Our review found no difference between placebo and any other topical treatment in the assessment of systemic adverse events. However, this may reect an absence of evidence (trials failing to appropriately assess these events over adequate time periods) rather than being evidence of absence. Although current evidence demonstrates that topical steroids are as effective and as well tolerated as vitamin D analogues, concern remains about the potential safety problems associated with corticosteroids (Bos 2008). Concerns include the risk of rebound (a worsening of disease following treatment discontinuation), skin atrophy (skin thinning) and tachyphylaxis (decreasing response to the drug) after long-term use (Hengge 2006). Methods to assess rebound have been developed and should be used in future research (Carey 2006). Regarding skin thinning, one problem with psoriasis is that the skin is very thick and a goal of therapy is to reduce the thickness of lesional (epidermal) skin. Damage to the surrounding normal skin may occur, and for that reason, topical corticosteroids should be used for limited periods or sparingly in delicate areas such as the face or folds of the skin. We found no evidence on tachyphylaxis, but if treatment response were to decline
this could lead to over-use, increasing the risk of percutaneous absorption. As the evidence base on longer-term adverse effects in psoriasis is inadequate, the preferences of people with psoriasis and their attitudes to these perceived risks should inform treatment choice. Further research is required to inform approaches to longterm maintenance.
Implications for research

Evidence showing that treatments do improve the symptoms of psoriasis has focused mainly on treatments with relatively short duration. There is limited randomised evidence to tell us about the long-term effect of using these treatments; good quality head-tohead evidence is therefore needed to quantify and compare longterm adverse events and to explore the feasibility of long-term treatment. There are important sources of heterogeneity in these trials, which it is not possible to explore in anything other than a qualitative sense. For example, the properties of the vehicle preparation are known to deliver wide variation in response to treatment. This is important when interpreting the ndings of this review. The value of the active ingredient may be one point on an IAGI but possibly one to two points are also being contributed by the vehicle. However, an analysis of vehicle performance was outside the scope of the review. Reporting standards within trials were generally suboptimal by todays standards and it would be useful to ensure that current trials adhere to CONSORT standards to help future reviews to interpret ndings appropriately. For example, where trials enrol participants with a wide range of baseline severity, stratifying the randomisation by baseline severity would be a useful design feature. We are not aware of studies that have adopted this approach. Triallists might usefully consider including more homogeneous participant groups in terms of severity, so that the clinical implications of ndings are clearer.
ACKNOWLEDGEMENTS
The editorial base would like to thank the following people who were external referees for this review: Sangeeta Amladi (content expert), Nicola Thornton (consumer). The review team are indebted to Jane Harrison (formerly of the Centre for Reviews and Dissemination, University of York) for devising the original search strategies in 1999; to Julie Glanville (formerly of the Centre for Reviews and Dissemination, University of York) and for running the effectiveness and adverse events search strategies in 2002 and 2005; to Kate Light (Centre for Reviews and Dissemination, University of York) for updating the searches in 2008, and to Finola Delamere of the Cochrane Skin Group for searching the Cochrane Skin Groups Specialist Skin Trials Register.
48
REFERENCES
References to studies included in this review

Agrup 1981 {published data only} Agrup G, Bjornberg A, Elmros T, Groth O, Hannuksela M, Lassus A, et al.Clinical Trial of a Potent Non-Halogenated Topical Steroid, Budesonide. Acta Dermato Venereologica 1981;61(2):1802. [PUBMED: 6165205] Austad 1998 {published and unpublished data} Austad J, Bjerke JR, Gjertsen BT, Helland S, Livden JK, Morken T, et al.Clobetasol Propionate Followed by Calcipotriol Is Superior to Calcipotriol Alone in Topical Treatment of Psoriasis. Journal of the European Academy of Dermatology & Venereology 1998;11(1):1924. [PUBMED: 9731961] Baiocchi 1997 {published data only} Baiocchi R, Bertani E, Biggio P, Calandra P, De Marchi R, Franchi A, et al.Controlled Trial of the Efcacy and Safety of Calcipotriol Ointment Applied Once or Twice a Day in Psoriasis Vulgaris Studio [Controllato Per Emiparti Sullefcacia E La Tollerabilita Di Calcipotriolo Unguento 1 Applicazione/Die Versus 2 Applicazioni/Die, Nella Psoriasi Volgare]. Giornale Italiano di Dermatologia e Venereologia 1997;132(2):13947. Barker 1999 (H) {published and unpublished data} Barker N, Ashton RE, Marks R, Harris RI, Berth-Jones J. Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-nding study with active comparator. British Journal Of Dermatology 1999;141 (2):2748. [MEDLINE: 10468799] Barker 1999 (P) {published and unpublished data} Barker N, Ashton RE, Marks R, Harris RI, Berth-Jones J. Topical maxacalcitol for the treatment of psoriasis vulgaris: a placebo-controlled, double-blind, dose-nding study with active comparator. British Journal Of Dermatology 1999;141 (2):2748. [PUBMED: 10468799] Berth-Jones J. Maxacalcitol - a new, potent and safe vitamin D analogue for treatment of psoriasis. British Journal Of Dermatology 1999;141:992. Bernhard 1991 (1) {published data only} Bernhard J, Whitmore C, Guzzo C, Kantor I, Kalb RE, Ellis C, et al.Evaluation of Halobetasol Propionate Ointment in the Treatment of Plaque Psoriasis: Report on Two Double-Blind, Vehicle-Controlled Studies. Journal of the American Academy of Dermatology 1991;25(6 Pt 2):11704. [PUBMED: 1757612] Bernhard 1991(2) {published data only} Bernhard J, Whitmore C, Guzzo C, Kantor I, Kalb RE, Ellis C, et al.Evaluation of Halobetasol Propionate Ointment in the Treatment of Plaque Psoriasis: Report on Two Double-Blind, Vehicle-Controlled Studies. Journal of the American Academy of Dermatology 1991;25(6 Pt 2):11704. [PUBMED: 1757612]
Berth Jones 1992b {published data only} Berth Jones J, Chu AC, Dodd WA, Ganpule M, Grifths WA, Haydey RP, et al.A Multicentre, Parallel-Group Comparison of Calcipotriol Ointment and Short-Contact Dithranol Therapy in Chronic Plaque Psoriasis. British Journal Of Dermatology 1992;127(3):26671. [PUBMED: 1390171] Bourke 1993b {published data only} Bourke JF, Berth-Jones J, Hutchinson PE. Occlusion enhances the efcacy of topical calcipotriol in the treatment of psoriasis vulgaris. Clinical & Experimental Dermatology 1993;18(6):5046. [PUBMED: 8252786] Bourke 1997 {published and unpublished data} Bourke JF, Featherstone S, Iqbal SJ, Hutchinson PE. A Double-Blind Comparison of Topical Calcitriol (3 mcg/g) and Calcipotriol (50 mcg/g) in the Treatment of Chronic Plaque Psoriasis Vulgaris. British Journal Of Dermatology 1995;133(Suppl 45):17. Bourke JF, Iqbal SJ, Hutchinson PE. A Randomized Double-Blind Comparison of the Effects on Systemic Calcium Homeostasis of Topical Calcipotriol (3 Mu G/G) and Calcipotriol (50 U M/G) in the Treatment of Chronic Plaque Psoriasis Vulgaris. Acta Dermato Venereologica 1997; 77(3):22830. [PUBMED: 9188878] Bruce 1994 {published and unpublished data} Bruce S, Epinette WW, Funicella T, Ison A, Jones EL, Loss RJ, et al.Comparative Study of Calcipotriene (Mc 903) Ointment and Fluocinonide Ointment in the Treatment of Psoriasis. Journal of the American Academy of Dermatology 1994;31(5 Pt 1):7559. [PUBMED: 7929921] Siskin SB. Efcacy and Safety of Calcipotriol Ointment Compared to Fluocinonide. 2nd International Symposium on Calcipotriol. Monaco, 1993. Buckley 1978 {published data only} Buckley DB. A Double-Blind Comparison of 0.1% Dithranol in a 17% Urea Base (Psoradrate) and Base Alone in the Treatment of Active Chronic Psoriasis. Current Medical Research & Opinion 1978;5(6):48994. [PUBMED: 350501 ] Camarasa 2003 {published data only} Camarasa JM, Ortonne JP, Dubertret L. Calcitriol shows greater persistence of treatment effect than betamethasone dipropionate in topical psoriasis therapy. Journal of Dermatological Treatment 2003;14(1):813. [PUBMED: 12745849] Cannavo 2003 {published and unpublished data} Cannavo SP, Guarneri F, Vaccaro M, Borgia F, Guarneri B. Treatment of psoriatic nails with topical cyclosporin: a prospective, randomized placebo-controlled study. Dermatology 2003; Vol. 206, issue 2:1536. [MEDLINE: 12592084] Cannavo SP, Guarneri F, Vaccaro M, Borgia FAD, Institute of Dermatology University of Messina Italy. Treatment of psoriatic nails with topical cyclosporin. 11th Congress of
49
the European Academy of Dermatology and Venereology. 2002:P2789. Cheesbrough 1992 {published data only} Cheesbrough MJ. Treatment of psoriasis with 30% Dead Sea salt lotion. Journal Of Dermatological Treatment 1992;3 (4):201203. [EMBASE: 1993020259] Christensen 1999 {published data only} Christensen OB, Mork NJ, Ashton R, Daniel F, Anehus S. Comparison of a treatment phase and a follow-up phase of short-contact dithranol and calcipotriol in outpatients with chronic plaque psoriasis. Journal Of Dermatological Treatment 1999;10(4):261265. [EMBASE: 2000044219] Crosti 1997 {published data only} Crosti C, Finzi AF, Mian E, Scarpa C. Calcipotriol in psoriasis vulgaris: a controlled trial comparing betamethasone dipropionate + salicylic acid. International Journal Of Dermatology 1997;36(7):5379. [PUBMED: 9268756] Cunliffe 1992 {published data only} Cunliffe WJ, Berth Jones J, Claudy A, Fairiss GM, Goldin D, Gratton D, et al.Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris. Journal of the American Academy of Dermatology 1992;26(5 Pt 1):73643. [MEDLINE: 1583173] De Simone 1993 {published data only} De Simone C, Guerriero C, Morini P, Venier A. Treatment of Psoriasis with Topical Calcipotriol [Il Calcipotriol Nella Terapia Locale Della Psoriasi]. Giornale Italiano di Dermatologia e Venereologia 1993;128(10):IcCiii. Douglas 2002 {published and unpublished data} Douglas WS, Poulin Y, Decroix J, Ortonne JP, Mrowietz U, Gulliver W, et al.A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris. Acta Dermato Venereologica 2002;82(2):1315. [PUBMED: 12125943 ] Dubertret 1992 {published and unpublished data} Dubertret L, Wallach D, Souteyrand P, Perussel M, Kalis B, Meynadier J, et al.Efcacy and Safety of Calcipotriol (Mc 903) Ointment in Psoriasis Vulgaris. A Randomized, Double-Blind, Right/Left Comparative, Vehicle-Controlled Study. Journal of the American Academy of Dermatology 1992;27(6 Pt 1):9838. [PUBMED: 1479106] Durakovic 2001 {published data only} Durakovic C, Malabanan A, Holick MF. Rationale for use and clinical responsiveness of hexauoro-1,25dihydroxyvitamin D3 for the treatment of plaque psoriasis: a pilot study. British Journal Of Dermatology 2001;144(3): 5006. [PUBMED: 11260006] Durakovic 2004 {published data only} Durakovic C, Ray S, Holick MF. Topical paricalcitol (19nor-1 alpha,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study. British Journal of Dermatology 2004;151(1):1905. [PUBMED: 15270890]
Duweb 2000 {published data only} Duweb GA, Abuzariba O, Rahim M, al-Taweel M, Abdulla SA. Scalp psoriasis: topical calcipotriol 50 micrograms/ g/ml solution vs. betamethasone valerate 1% lotion. International Journal of Clinical Pharmacology Research 2000;20(3-4):658. [PUBMED: 11314240 ] Elie 1983 {published data only} Elie R, Durocher LP, Kavalec EC. Effect of Salicylic Acid on the Activity of Betamethasone-17,21-Dipropionate in the Treatment of Erythematous Squamous Dermatoses. Journal of International Medical Research 1983;11(2):10812. [PUBMED: 6852357 ] Ellis 1988 {published data only} Ellis CN, Horwitz SN, Menter A. Amcinonide Lotion 0.1% in the Treatment of Patients with Psoriasis of the Scalp. Current Therapeutic Research - Clinical and Experimental 1988;44(2):315324. [EMBASE: 1989232557] Escobar 1992 {published data only} Escobar SO, Achenbach R, Iannantuono R, Torem V. Topical sh oil in psoriasis--a controlled and blind study. Clinical & Experimental Dermatology 1992;17(3):15962. [PUBMED: 1451289 ] Farkas 1999 {published and unpublished data} Farkas B, Dobozy A. Comparison of Tacalcitol with Dithranol. 3rd European Hermal Symposium. Hamburg, 1995. Farkas B, Dobozy A, Horvath A, Hunyadi J, Schneider I. Comparison of tacalcitol ointment with short-contact dithranol therapy in the treatment of psoriasis vulgaris: a randomized multicentre, open prospective study on efcacy and safety. Journal Of Dermatological Treatment 1999;10: 939. [EMBASE: 1999259658] Franz 1999 {published data only} Franz TJ, Parsell DA, Halualani RM, Hannigan JF, Kalbach JP, Harkonen WS. Betamethasone valerate foam 0.12%: a novel vehicle with enhanced delivery and efcacy. International Journal Of Dermatology 1999;38(8):62832. [PUBMED: 10487457 ] Franz 2000 {published data only} Franz TJ, Parsell DA, Myers JA, Hannigan JF. Clobetasol propionate foam 0.05%: a novel vehicle with enhanced delivery. International Journal Of Dermatology 2000;39(7): 5358. [PUBMED: 10940121 ] Geilen 2000 {published data only} Geilen CC, Mrowietz U. Lack of efcacy of topical mycophenolic acid in psoriasis vulgaris. Journal of the American Academy of Dermatology 2000;42(5 Pt 1):83740. [PUBMED: 10775867 ] Gottlieb 2003 {published data only} Gottlieb AB, Ford RO, Spellman MC. The efcacy and tolerability of clobetasol propionate foam 0.05% in the treatment of mild to moderate plaque-type psoriasis of nonscalp regions. Journal of Cutaneous Medicine & Surgery 2003;7(3):18592. [PUBMED: 12704534 ]
50
Grattan 1997 (H) {published data only} Grattan CEH, Hallam F, Whiteeld M. A New Aqueous Dithranol Gel for Psoriasis: Comparison with Placebo and Calcipotriol Ointment. Journal Of Dermatological Treatment 1997;8(1):115. [EMBASE: 1997109958] Grattan 1997 (P) {published data only} Grattan CEH, Hallam F, Whiteeld M. A New Aqueous Dithranol Gel for Psoriasis: Comparison with Placebo and Calcipotriol Ointment. Journal Of Dermatological Treatment 1997;8(1):115. [EMBASE: 1997109958] Green 1994 {published and unpublished data} Green C, Ganpule M, Harris D, Kavanagh G, Kennedy C, Mallett R, et al.Comparative Effects of Calcipotriol (Mc903) Solution and Placebo (Vehicle of Mc903) in the Treatment of Psoriasis of the Scalp. British Journal Of Dermatology 1994;130(4):4837. [PUBMED: 8186114 ] Greenspan 1993 {published and unpublished data} Greenspan A, Herndon JJ, Baker MD, Cheney T. Controlled Evaluation of 0.05% Desonide Lotion and Desonide Cream in Psoriasis. Current Therapeutic Research Clinical and Experimental 1993;53(6):614620. [EMBASE: 1993261649] Gribetz 2004 {published and unpublished data} Gribetz C, Ling M, Lebwohl M, Pariser D, Draelos Z, Gottlieb AB, et al.Pimecrolimus cream 1% in the treatment of intertriginous psoriasis: A double-blind, randomized study. Journal of the American Academy of Dermatology 2004;51(5):7318. [PUBMED: 15523351] Guenther 2000 {published data only} Guenther LC, Poulin YP, Pariser DM. A comparison of tazarotene 0.1% gel once daily plus mometasone furoate 0.1% cream once daily versus calcipotriene 0.005% ointment twice daily in the treatment of plaque psoriasis. Clinical Therapeutics 2000;22(10):122538. [PUBMED: 11110233] Guenther 2002 (H) {published and unpublished data} Guenther L, Van De Kerkhof PCM, Kragballe K, Chu AC, Tegner E, Garcia-Diez A, et al.Efcacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial. British Journal Of Dermatology 2002;147(2):31623. [PUBMED: 12174105] van de Kerkhof PC. The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet/ Dovobet) on the quality of life in patients with psoriasis vulgaris: a randomized controlled trial. British Journal of Dermatology 2004;151(3):6638. [PUBMED: 15377355] van de Kerkhof PCM. A xed combination of calcipotriol/ betamethasone dipropionate improves quality of life in patients with psoriasis vulgaris. 11th Congress of the European Academy of Dermatology and Venereology. 2002:P272.
Guenther 2002 (P) {published and unpublished data} Guenther L, Van De Kerkhof PCM, Kragballe K, Chu AC, Tegner E, Garcia-Diez A, et al.Efcacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial. British Journal Of Dermatology 2002;147(2):31623. [PUBMED: 12174105] van de Kerkhof PC. The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet/ Dovobet) on the quality of life in patients with psoriasis vulgaris: a randomized controlled trial. British Journal of Dermatology 2004;151(3):6638. [MEDLINE: 15377355] van de Kerkhof PCM. A xed combination of calcipotriol/ betamethasone dipropionate improves quality of life in patients with psoriasis vulgaris. 11th Congress of the European Academy of Dermatology and Venereology. 2002:P272. Han 2001 {published data only} Han GW, Yu BT, Li H, Zhu XJ, Wang BX, Li GM, et al.A randomized controlled multicenter clinical trial on tazarotene gel versus calcipotriol ointment in the treatment of plaque psoriasis vulgaris. The Chinese Journal of Clinical Pharmacology 2001;17(6):41922. Harrington 1996a {published data only} Harrington CI, Goldin D, Lovell CR, Van De Kerkhof P, Nieboer C, Austad J, et al.Comparative Effects of Two Different Calcipotriol (Mc 903) Cream Formulations Versus Placebo in Psoriasis Vulgaris. A Randomised, DoubleBlind, Placebo-Controlled, Parallel Group Multi-Centre Study 1. Journal of the European Academy of Dermatology & Venereology 1996;6(2):1528. [EMBASE: 1996096735] Henneicke-v. Z. 1993 {published data only} Henneicke-von Zepelin HH, Mrowietz U, Farber L, BruckBorchers K, Schober C, Huber J, et al.Highly puried omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. British Journal Of Dermatology 1993;129 (6):7137. [PUBMED: 8286257] Highton 1995 {published data only} Highton A, Quell J, Breneman D, Cullen S, Goffe B, Grifths C, et al.Calcipotriene ointment 0.005% for psoriasis: A safety and efcacy study. Journal of the American Academy of Dermatology 1995;32(1):6772. [PUBMED: 7822519] Holick 2003 {published data only} Holick MF, Chimeh FN, Ray S. Topical PTH (1-34) is a novel, safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial. British Journal of Dermatology 2003;149(2):3706. [PUBMED: 12932245] Hutchinson 2000 {published data only} Hutchinson PE, Marks R, White J. The efcacy, safety and tolerance of calcitriol 3 &mgr;g/g ointment in the
51
treatment of plaque psoriasis: a comparison with shortcontact dithranol. Dermatology 2000;201(2):13945. [PUBMED: 11053917] Jarratt 2004 {published data only} Jarratt M, Breneman D, Gottlieb AB, Poulin Y, Liu Y, Foley V. Clobetasol propionate shampoo 0.05%: a new option to treat patients with moderate to severe scalp psoriasis. Journal of Drugs in Dermatology: JDD 2004;3(4):36773. [PUBMED: 15303780] Jekler 1992 {published data only} Jekler J, Swanbeck G. One-Minute Dithranol Therapy in Psoriasis: A Placebo-Controlled Paired Comparative Study. Acta Dermato Venereologica 1992;72(6):44950. [PUBMED: 1362841] Jin 2001 {published data only} Jin HZ, Wang JB, He ZX, Xie Y. A Randomized, Placebo, Controlled,Double Blind Trial Study on IL-8 Monoclonal Antibody Cream in the Treatment of Psoriasis Vulgaris. The Chinese Journal of Clinical Pharmacology 2001;17(1):3640. Jorizzo 1997 {published data only} Jorizzo Jl, Magee K, Stewart DM, Lebwohl MG, Rajagopalan R, Brown JJ. Clobetasol propionate emollient 0.05 percent: hypothalamic-pituitary-adrenal-axis safety and four-week clinical efcacy results in plaque-type psoriasis. Cutis 1997;60(1):5560. [PUBMED: 9252738] Kang 1998 {published and unpublished data} Kang S, Yi S, Grifths CEM, Fancher L, Hamilton TA, Choi JH. Calcipotriene-Induced Improvement in Psoriasis Is Associated with Reduced Interleukin-8 and Increased Interleukin-10 Levels within Lesions. British Journal Of Dermatology 1998;138(1):7783. [PUBMED: 9536226] Kanzler 1993 {published and unpublished data} Kanzler MH, Gorsulowsky DC. Efcacy of topical 5% liquor carbonis detergens vs. its emollient base in the treatment of psoriasis. British Journal Of Dermatology 1993; 129(3):3104. [PUBMED: 8286230] Katz 1987a {published data only} Katz HI, Hien NT, Prawer S, Scot JC, Grivna EM. Betamethasone Dipropionate in Optimized Vehicle. Intermittent Pulse Dosing for Extended Maintenance Treatment of Psoriasis. Archives of Dermatology 1987;123 (10):130811. [PUBMED: 3662562] Katz 1991a {published data only} Katz HI, Prawer SE, Medansky RS, Krueger GG, Mooney JJ, Jones ML, et al.Intermittent corticosteroid maintenance treatment of psoriasis: a double-blind multicenter trial of augmented betamethasone dipropionate ointment in a pulse dose treatment regimen. Dermatologica 1991;183(4): 26974. [PUBMED: 1809589] Katz 1991b {published data only} Katz HI, Gross E, Buxman M, Prawer SE, Schwartzel EH, Gibson JR. A double-blind, vehicle-controlled paired comparison of halobetasol propionate cream on patients with plaque psoriasis. Journal of the American Academy of Dermatology 1991;25(6 Pt 2):11758. [PUBMED: 1757613]
Kaufmann 2002 (H) {published and unpublished data} Kaufmann R, Bibby AJ, Bissonnette R, Cambazard F, Chu AC, Decroix J, et al.A New Calcipotriol/Betamethasone Dipropionate Formulation (Daivobet(TM)) Is an Effective Once-Daily Treatment for Psoriasis vulgaris. Dermatology 2002;205(4):38993. [PUBMED: 12444337] Kaufmann 2002 (P) {published and unpublished data} Kaufmann R, Bibby AJ, Bissonnette R, Cambazard F, Chu AC, Decroix J, et al.A New Calcipotriol/Betamethasone Dipropionate Formulation (Daivobet(TM)) Is an Effective Once-Daily Treatment for Psoriasis vulgaris. Dermatology 2002;205(4):38993. [PUBMED: 12444337] Kim 1994 {published data only} Kim JY, You YH, Kim TY, Kim CW. Comparative Study of Calcipotriol and Desoxymethasone Ointments in the Treatment of Psoriasis Vulgaris. The Clinical Effect and Immunohistochemical Change. Korean Journal of Dermatology 1994;32(6):105463. [EMBASE: 1995058111] Kiss 1996 {published data only} Carder KR. A randomized double blind parallel group dose-ranging comparison of the efcacy and safety of calcipotriene solution in the treatment of scalp psoriasis. Abstract 844. Journal of Investigative Dermatology 1996;106 (4):946. Kiss I, McCreary HL, Siskin SB, Epinette WW. A Randomized, Double- Blind, Parallel Group, Dose-Ranging Comparison of the Efcacy and Safety of Calcipotriene Solution in the Treatment of Scalp Psoriasis. American Academy of Dermatology, 54th annual Meeting. 1996; Vol. Poster abstract P301. Klaber 1994 {published data only} Klaber MR, Hutchinson PE, Pedvis-Leftick A, Kragballe K, Reunala TL, Van de Kerkhof PC, et al.Comparative effects of calcipotriol solution (50 micrograms/ml) and betamethasone 17-valerate solution (1 mg/ml) in the treatment of scalp psoriasis. British Journal Of Dermatology 1994;131(5):67883. [PUBMED: 7999600] Klaber 2000b {published and unpublished data} Klaber MR, McKinnon C. Calcipotriol (DovonexR) scalp solution in the treatment of scalp psoriasis: Comparative efcacy with 1% coal tar/1% coconut oil/0.5% salicylic acid (CapasalR) shampoo, and long-term experience. Journal Of Dermatological Treatment 2000;11(1):218. [EMBASE: 2000114933] Kragballe 1988b {published and unpublished data} Kragballe K, Beck HI, Sgaard H. Improvement of Psoriasis by a Topical Vitamin D3 Analogue (Mc 903) in a DoubleBlind Study. British Journal Of Dermatology 1988;119(2): 22330. [EMBASE: 1988203615] Kragballe 1991a {published and unpublished data} Kragballe K, Gjertsen BT, De Hoop D, Karlsmark T, van de Kerkhof PC, Larko O, et al.Double-blind, right/left comparison of calcipotriol and betamethasone valerate in treatment of psoriasis vulgaris. Lancet 1991;337(8735): 1936. [PUBMED: 1670840]
52
Kragballe 1998b {published and unpublished data} Glade CP, Van Erp PE, Van De Kerkhof PC. Epidermal cell DNA content and intermediate laments keratin 10 and vimentin after treatment of psoriasis with calcipotriol cream once daily, twice daily and in combination with clobetasone 17-butyrate cream or betamethasone 17-valerate cream: a comparative ow cytometric study. British Journal Of Dermatology 1996;135(3):37984. [PUBMED: 8949429] Kragballe K, Barnes L, Hamberg KJ, Hutchinson P, Murphy F, Moller S, et al.Calcipotriol Cream with or without Concurrent Topical Corticosteroid in Psoriasis: Tolerability and Efcacy. British Journal Of Dermatology 1998;139(4):64954. [MEDLINE: 9892908] van de Kerkhof PC. Calcipotriol cream and concurrent corticosteroids in psoriasis. Journal of the European Academy of Dermatology & Venereology 1995; Vol. 5, issue Suppl 1:S184. Kragballe 2004 {published data only} Kragballe K, Noerrelund KL, Lui H, Ortonne JP, Wozel G, Uurasmaa T, et al.Efcacy of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment and calcipotriol ointment in psoriasis vulgaris. British Journal of Dermatology 2004;150(6):116773. [PUBMED: 15214905] Krueger 1998 {published data only} Krueger GG, Drake LA, Elias PM, Lowe NJ, Guzzo C, Weinstein GD, et al.The safety and efcacy of tazarotene gel, a topical acetylenic retinoid, in the treatment of psoriasis. Archives of Dermatology 1998;134(1):5760. [PUBMED: 9449910] Kse 1997 {published data only} Kse O. Calcipotriol ointment vs clobetasol solution in scalp psoriasis. Journal Of Dermatological Treatment 1997;8: 287. [EMBASE: 1998022654] Landi 1993 {published data only} Landi G. Efcacy and safety of calcipotriol ointment compared to clobetasol ointment in psoriasis vulgaris. 3rd congress of the European Academy of Dermatology and Venereology. Copenhagen, Denmark, 1993:199. Landi G, Pierleoni M, Polverelli M, Fioravanti F. Calcipotriol, a New Topical Product in the Therapy of Psoriasis: Controlled Study Versus Clobetasol [Il Calcipotriol, Nuovo Topico Nella Terapia Della Psoriasi: Studio Controllato Versus Clobetasol]. Giornale Italiano di Dermatologia e Venereologia 1993;128(9):8993. [EMBASE: 1993360641] Lane 1983 {published data only} Lane AT, Wachs GN, Weston WL. Once-Daily Treatment of Psoriasis with Topical Glucocorticosteroid Ointments. Journal of the American Academy of Dermatology 1983;8(4): 5235. [PUBMED: 6853785] Langner 1992 {published data only} Langner A, Verjans H, Stapor V, Mol M, Fraczykowska M. 1 Alpha ,25-Dihydroxyvitamin D-3 (Calcitriol) Ointment in Psoriasis. Journal Of Dermatological Treatment 1992;3(4): 177180. [EMBASE: 1993020253]
Langner 1993 {published data only} Langner A, Verjans H, Stapor V, Mol M, Fraczykowska M. Topical Calcitriol in the Treatment of Chronic Plaque Psoriasis: A Double-Blind Study. British Journal Of Dermatology 1993;128(5):56671. [PUBMED: 8504051] Langner 2001 (H) {published data only} Langner A, Stapor W, Ambroziak M. Efcacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland. British Journal Of Dermatology 2001;58:1116. [PUBMED: 11501507] Langner 2001 (P) {published data only} Langner A, Stapor W, Ambroziak M. Efcacy and tolerance of topical calcitriol 3 microg g(-1) in psoriasis treatment: a review of our experience in Poland. British Journal Of Dermatology 2001;58:1116. [PUBMED: 11501507] Lassus 1991 {published data only} Lassus A, Forsstrom S. A double-blind study comparing oleum horwathiensis with placebo in the treatment of psoriasis. Journal of International Medical Research 1991;19 (2):13746. [PUBMED: 1864450] Lebwohl 2002 {published data only} Lebwohl M, Scher RK, Washenik K, Krueger G, Menter A, Koo J, et al.A randomized, double-blind placebo-controlled study of the safety and efcacy of clobetasol propionate 0.05% foam in the treatment of non-scalp psoriasis.. Skin Pharmacology & Applied Skin Physiology 2001;14:168. Lebwohl M, Sherer D, Washenik K, Krueger GG, Menter A, Koo J, Feldman SR. A randomized, double-blind, placebo-controlled study of clobetasol propionate 0.05% foam in the treatment of nonscalp psoriasis. International Journal Of Dermatology 2002;41(5):269274. [PUBMED: 12100701] Lebwohl 2004 {published data only} Lebwohl M, Freeman AK, Chapman MS, Feldman SR, Hartle JE, Henning A. Tacrolimus ointment is effective for facial and intertriginous psoriasis. Journal of the American Academy of Dermatology 2004;51(5):72330. [PUBMED: 15523350] Lepaw 1978 {published data only} Lepaw MI. Double-Blind Comparison of Halcinonide Solution and Placebo Control in Treatment of Psoriasis of the Scalp. Cutis 1978;21(4):5713. [PUBMED: 346315] Lister 1997 {published data only} Lister RK, Woodrow Sl, Hughes JH, Cerio R, Norris PG, Grifths CEM, et al.Can dithranol have a lasting effect and be more acceptable to patients? Micanol Cream - a trial of 171 patients with psoriasis. British Journal of Dermatology 1997;137(Suppl 50):17. Medansky 1987 {published data only} Medansky RS, Brody NI, Kanof NB, Russo GJ, Peets EA. Clinical Investigations of Mometasone Furoate - a Novel Nonuorinated, Topical Corticosteroid. Seminars In Dermatology 1987;6(2):94100. [EMBASE: 1988051740] Medansky 1996 {published data only} Medansky RS, Greenspan A, Kraus SJ, Todd Plott R. The Comparative Efcacy of Diorasone Diacetate
53
Ointment 0.05% (Psorcon) vs Calcipotriene Ointment (Dovonex) in the Treatment of Psoriasis. Journal of Geriatric Dermatology 1996;4(1):2024. Molin 1997 {published and unpublished data} Molin L, Cutler TP, Helander I, Nyfors B. Calcipotriol cream and betamethasone valerate cream of equal efcacy in psoriasis. Journal of the European Academy of Dermatology & Venereology 1995;5(Suppl 1):S92. Molin L, Cutler TP, Helander I, Nyfors B. Comparative Efcacy of Calcipotriol Cream and Betamethasone Valerate Cream in the Treatment of Psoriasis. Journal of Investigative Dermatology. Symposium Proceedings 1996;1(1):110. Molin L, Cutler TP, Helander I, Nyfors B, Downes N. Comparative Efcacy of Calcipotriol (Mc903) Cream and Betamethasone 17-Valerate Cream in the Treatment of Chronic Plaque Psoriasis. A Randomized, DoubleBlind, Parallel Group Multicentre Study. Calcipotriol Study Group. British Journal Of Dermatology 1997;136(1):8993. [PUBMED: 9039301] Monastirli 2000 {published data only} Monastirli A, Zografakis CH, Braun H, Pasmatzi E, Georgiou S, Sakkis TH, et al.Calcipotriol vs. Anthralin in the treatment of chronic plaque psoriasis. H+G Zeitschrift Fur Hautkrankheiten. 2000;75(11):6269. [EMBASE: 2000428558] Mortensen 1993b {published and unpublished data} Mortensen L, Kragballe K, Wegmann E, Schifter S, Risteli J, Charles P. Treatment of Psoriasis Vulgaris with Topical Calcipotriol Has No Short-Term Effect on Calcium or Bone Metabolism. A Randomized, Double-Blind, PlaceboControlled Study. Acta Dermato Venereologica 1993;73(4): 3004. [PUBMED: 7904106] Olsen 1991 {published data only} Olsen EA, Cram DL, Ellis CN, Hickman JG, Jacobson C, Jenkins EE, et al.A double-blind, vehicle-controlled study of clobetasol propionate 0.05% (Temovate) scalp application in the treatment of moderate to severe scalp psoriasis. Journal of the American Academy of Dermatology 1991;24(3): 4437. [PUBMED: 2061442] Olsen 1996 (1) {published data only} Olsen EA. Efcacy and Safety of Fluticasone Propionate 0.005% Ointment in the Treatment of Psoriasis. Cutis 1996;57(2 Suppl):5761. [PUBMED: 8646872] Olsen 1996 (2) {published data only} Olsen EA. Efcacy and Safety of Fluticasone Propionate 0.005% Ointment in the Treatment of Psoriasis. Cutis 1996;2 Suppl:5761. [PUBMED: 8646872] Oranje 1997 {published data only} Oranje AP, Marcoux DS, A, Prendiville J, Krafchik B, Toole J, Rosenthal D, et al.Topical calcipotriol in childhood psoriasis. Journal of the American Academy of Dermatology 1997;36(2 Pt 1):2038. [PUBMED: 9039169] Ormerod 1997 {published and unpublished data} Ormerod AD, Dwyer CM, Weller R, Cox DH, Price R. A comparison of subjective and objective measures of reduction of psoriasis with the use of ultrasound, reectance
colorimetry, computerized video image analysis, and nitric oxide production. Journal of the American Academy of Dermatology 1997;37(1):517. [PUBMED: 9216523 ] Ormerod 2000 {published data only} Ormerod AD, Copeland P, Shah SA. Treatment of psoriasis with topical NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis. British Journal Of Dermatology 2000; 142(5):98590. [PUBMED: 10809860] Ormerod 2005 {published data only} Ormerod AD, Shah SA, Copeland P, Omar G, Wineld A. Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial. British Journal of Dermatology 2005;152(4):75864. [PUBMED: 15840110 ] Ortonne 1994 {published data only} Ortonne JP, Bazex J, Binet O, Bombart M, Brun P, Carreau O, et al.Psoriasis: New Therapeutic Modality by Calcipotriol and Betamethasone Dipropionate. Nouvelles Dermatologiques 1994;13(10):74651. [EMBASE: 1995010294] Ortonne 2003 {published data only} Nicolas JF. Calcitriol vs calcipotriol in psoriasis of sensitive areas Abstract. 20th World Congress of Dermatology. Paris, 2002:SA1048. Ortonne JP, Humbert P, Nicolas JF, Tsankov N, Tonev SD, Janin A, et al.Intra-individual comparison of the cutaneous safety and efcacy of calcitriol 3 microg g(-1) ointment and calcipotriol 50 microg g(-1) ointment on chronic plaque psoriasis localized in facial, hairline, retroauricular or exural areas. British Journal of Dermatology 2003;148(2): 32633. [PUBMED: 12588387] Ortonne 2004 {published and unpublished data} Ortonne JP, Kaufmann R, Lecha M, Goodeld M. Efcacy of treatment with calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with tacalcitol for the treatment of psoriasis vulgaris: A randomised, double-blind trial. Dermatology (Basel) 2004; 209(4):30813. [PUBMED: 15539894] Ortonne JP, Traulsen J, Kaufmann R, Lecha M, Goodeld M. Calcipotriol/betamethasone dipropionate ointment once daily versus tacalcitol once daily in psoriasis vulgaris. Abstract P27-49 The 12th Congress of the European Academy of Dermatology and Venereology. Barcelona, Spain 15-18th October 2003. Journal of the European Academy of Dermatology & Venereology. 2003; Vol. 17, issue Suppl 3:374. Papp 2003 (H) {published and unpublished data} Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ, et al.Early onset of action and efcacy of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis. Journal of the American Academy of Dermatology 2003;48(1):4854. [PUBMED: 12522370] Papp 2003 (P) {published and unpublished data} Papp KA, Guenther L, Boyden B, Larsen FG, Harvima RJ, Guilhou JJ, et al.Early onset of action and efcacy
54
of a combination of calcipotriene and betamethasone dipropionate in the treatment of psoriasis. Journal of the American Academy of Dermatology 2003;48(1):4854. [PUBMED: 12522370] Pariser 1996 {published data only} Pariser DM, Pariser RJ, Breneman D, Lebwohl M, Kalb R, Moore J, Moss H, Parker C, Fiedler V. Calcipotriene ointment applied once a day for psoriasis: A doubleblind, multicenter, placebo-controlled study. Archives of Dermatology 1996;132(12):1527. [PUBMED: 8961897] Pauporte 2004 {published and unpublished data} Pauporte M, Maibach H, Lowe N, Pugliese M, Friedman DJ, Mendelsohn H, et al.Fluocinolone acetonide topical oil for scalp psoriasis. Journal of Dermatological Treatment 2004;15(6):3604. [PUBMED: 15764047] Perez 1996 {published and unpublished data} Perez A, Chen TC, Turner A, Raab R, Bhawan J, Poche P, et al.Efcacy and Safety of Topical Calcitriol (1,25Dihydroxyvitamin D3) for the Treatment of Psoriasis. British Journal Of Dermatology 1996;134(2):23846. [PUBMED: 8746336] Pinheiro 1997 {published and unpublished data} Pinheiro N. Comparative Effects of Calcipotriol Ointment (50 Micrograms/G) and 5% Coal Tar/2% Allantoin/0.5% Hydrocortisone Cream in Treating Plaque Psoriasis. British Journal of Clinical Practice 1997;51(1):169. [PUBMED: 9158266] Reygagne 2002b {published data only} Reygagne P, Mrowietz U, Decroix J, Van der Spek W, Olmos Acebes L, Figueiredo A, et al.Four-week efcacy and safety comparison of a new clobetasol shampoo and calcipotriol solution 0.005% in subjects with scalp psoriasis. 11th Congress of the European Academy of Dermatology and Venereology. 2002:P2736. Ruzicka 1998 {published data only} Ruzicka T, Kallinschnigg G, Lorenz B, Schroder G. Clinical Efcacy of a Monotherapy with Calcipotriol-Ointment Compared to Combination Therapy with Calcipotriol Ointment and Betamethasone Valerate Ointment in Psoriasis Vulgaris. Journal of Investigative Dermatology 1996; 1(1):107. Ruzicka T, Lorenz B. Comparison of Calcipotriol Monotherapy and a Combination of Calcipotriol and Betamethasone Valerate after 2 Weeks Treatment with Calcipotriol in the Topical Therapy of Psoriasis Vulgaris: A Multicentre, Double-Blind, Randomized Study. British Journal Of Dermatology 1998;138(2):2548. [PUBMED: 9602870] Salmhofer 2000 {published data only} Salmhofer W, Maier H, Soyer HP, Honigsmann H, Hodl S. Double-blind, placebo-controlled, randomized, right-left study comparing calcipotriol monotherapy with a combined treatment of calcipotriol and diucortolone valerate in chronic plaque psoriasis. Acta Dermato Venereologica. Supplementum 2000;211:58. [PUBMED: 11234559]
Sanchez 2001 {published and unpublished data} Sanchez Regana M, Iglesias Sancho M, Umbert Millet P. Treatment of plague-type psoriasis with topical propylthiouracil. Actas Dermo Siliogracas 2001;92(4): 174176. [EMBASE: 2001206374] Santoianni 2001 {published data only} Santoianni P, Di Iorio S, Giannetti A, Manfredi G, Rebora A, Landi G, et al.Short-term clinical efcacy of the association betamethasone 17-valerate 21-acetate + tretinoine + salicylic acid in outpatients affected with disseminated keratotic plaque psoriasis: A double blinded placebo-controlled multicentric randomized clinical trial. Giornale Italiano di Dermatologia e Venereologia 2001;136 (1):7783. [EMBASE: 2001160666] Scarpa 1994 {published data only} Scarpa C. Calcipotriol: Clinical Trial Versus Betamethasone Dipropionate + Salicylic Acid. Acta Dermato Venereologica, Supplementum 1994;186:47. [PUBMED: 8073835] Scarpa 1996 {published data only} Scarpa C. Tacalcitol Ointment Is an Efcacious and Well Tolerated Treatment for Psoriasis. Journal of the European Academy of Dermatology & Venereology 1996;6(2):1426. [EMBASE: 1996096733] Scarpa C, Kokelj F, Plozzer C, Lavaroni G. Efcacy and Tolerability of Tacalcitol Ointment on Psoriatic Skin: Study in 63 Patients. Journal of Investigative Dermatology. Symposium Proceedings 1996;1(1):110. Scarpa 1997 {published data only} Scarpa C, Kokelj F, Plozzer C, Lavaroni G, Torsello P. Efcacy and Tolerability of Tacalcitol Administered Once Daily in the Treatment of Psoriasis Vulgaris (DoubleBlind, Randomized, Placebo Controlled Italian Multicenter Study). Giornale Italiano di Dermatologia e Venereologia 1997;132(5):3358. [EMBASE: 1997363332] Scher 2001 {published data only} Scher R. Tazarotene 0.1% gel in the treatment of nail psoriasis. Abstract. 20th World Congress of Dermatology. 2002:P0791. Scher RK, Stiller M, Zhu YI. Tazarotene 0.1% gel in the treatment of ngernail psoriasis: a double-blind, randomized, vehicle-controlled study. Cutis 2001;68(5): 3558. [PUBMED: 11766122 ] Scher RK, Stiller M, Zhu YI. Treating ngernail psoriasis with tazarotene 0.1% gel: A vehicle-controlled study. Skin Pharmacology & Applied Skin Physiology 2001;14(3):170. Sears 1997 {published data only} Sears HW, Bailer JW, Yeadon A. A Double-Blind, Randomized, Placebo-Controlled Evaluation of the Efcacy and Safety of Hydrocortisone Buteprate 0.1% Cream in the Treatment of Psoriasis. Advances In Therapy 1997;14(3): 1409. [EMBASE: 1997223749] Seidenari 1997 (H) {published data only} Seidenari S, Magni R, Giannetti A. Assessment of the Activity of Tacalcitol on Psoriatic Plaques by Means of Colorimetry and High-Frequency Ultrasound: A DoubleBlind Intrasubject Half-Side Right-Left Comparison with
55
Betamethasone Valerate and Placebo. Skin Pharmacology 1997;10(1):407. [EMBASE: 1997139265] Seidenari 1997 (P) {published data only} Seidenari S, Magni R, Giannetti A. Assessment of the Activity of Tacalcitol on Psoriatic Plaques by Means of Colorimetry and High-Frequency Ultrasound: A DoubleBlind Intrasubject Half-Side Right-Left Comparison with Betamethasone Valerate and Placebo. Skin Pharmacology 1997;10(1):407. [EMBASE: 1997139265] Shuttleworth 1998 {published data only} Shuttleworth D, Galloway DB, Boorman GC, A.E. D. A double-blind, placebo-controlled study of the clinical efcacy of ciclopirox olamine (1.5%) shampoo for the control of scalp psoriasis. Journal Of Dermatological Treatment 1998;9(3):1637. [EMBASE: 1998346163] Staberg 1998b {published data only} Staberg B, Roed-Petersen J, Menne T. Efcacy of Topical Treatment in Psoriasis with Mc903, a New Vitamin D Analogue. Acta Dermato Venereologica 1989;69(2):14750. [PUBMED: 2564233] Stein 2001 {published data only} Stein LF, Sherr A, Solodkina G, Gottlieb AB, Chaudhari U. Betamethasone valerate foam for treatment of nonscalp psoriasis. Journal of Cutaneous Medicine & Surgery 2001;5 (4):3037. [PUBMED: 11907840] Stuecker 2001 {published and unpublished data} Hoffmann M, Memmel U, Altmeyer P, Stuecker M. Topical treatment of chronic-stationary plaque psoriasis with vitamin B12. (Ger.). Zeitschrift Fur Hautkrankheiten 2001; Suppl. 1(76):S12. Stuecker M, Memmel U, Hoffmann M, Hartung J, Altmeyer P. Vitamin B(12) cream containing avocado oil in the therapy of plaque psoriasis. Dermatology 2001;203(2): 1417. [PUBMED: 11586013] Stutz 1996 {published data only} Stutz JA, N. EC, Kang S. Failure of topical polymyxin B to improve mild plaque psoriasis [letter]. Archives of Dermatology 1996;132(2):231. [PUBMED: 8629837] Sudilovsky 1981 {published data only} Sudilovsky A, Muir JG, Bocobo FC. A Comparison of Single and Multiple Applications of Halcinonide Cream. International Journal Of Dermatology 1981;20(9):60913. [PUBMED: 7030988] Sutton 2001 {published data only} Sutton L, Swinehart JM, Cato A, Kaplan AS. A clinical study to determine the efcacy and safety of 1% methotrexate/ Azone (MAZ) gel applied topically once daily in patients with psoriasis vulgaris. International Journal Of Dermatology 2001;40(7):4647. [MEDLINE: 11679005] Syed 1996 {published data only} Syed TA, Ahmad SA, Holt AH, Ahmad SA, Ahmad SH, Afzal M. Management of psoriasis with Aloe vera extract in a hydrophilic cream: a placebo-controlled, double-blind study. Tropical Medicine & International Health 1996;1(4): 5059. [PUBMED: 8765459]
Syed 2001b {published data only} Syed TA, Hadi SM, Qureshi ZA, Nordstrom CG, Ali SM. Management of psoriasis vulgaris with methotrexate 0.25% in a hydrophilic gel: a placebo-controlled, double-blind study. Journal of Cutaneous Medicine & Surgery 2001;5(4): 299302. [PUBMED: 11907839] Tham 1994 {published data only} Tham SN, Lun KC, Cheong WK. A comparative study of calcipotriol ointment and tar in chronic plaque psoriasis. British Journal Of Dermatology 1994;131(5):6737. [PUBMED: 7999599] Tosti 1998 {published data only} Tosti A, Piraccini BM, Cameli N, Kokely F, Plozzer C, Cannata GE, et al.Calcipotriol Ointment in Nail Psoriasis: A Controlled Double-Blind Comparison with Betamethasone Dipropionate and Salicylic Acid. British Journal Of Dermatology 1998;139(4):6559. [MEDLINE: 9892909] van de Kerkhof 1989 {published data only} van de Kerkhof PCM, van Bokhoven M, Zultak M, Czarnetzki BM. A Double-Blind Study of Topical 1 Alpha, 25-Dihydroxyvitamin D3 in Psoriasis. British Journal Of Dermatology 1989;120(5):6614. [PUBMED: 2667612] van de Kerkhof 1996a {published data only} van de Kerkhof PCM, Werfel T, Haustein UF, Luger T, Czarnetzki BM, Niemann R, et al.Tacalcitol Ointment in the Treatment of Psoriasis Vulgaris: A Multicentre, PlaceboControlled, Double- Blind Study on Efcacy and Safety. British Journal Of Dermatology 1996;135(5):75865. [PUBMED: 8977677] van de Kerkhof 2002a {published data only} van de Kerkhof PCM, Green C, Hamberg KJ, Hutchinson PE, Jensen JK, Kidson P, et al.Safety and efcacy of combined high-dose treatment with calcipotriol ointment and solution in patients with psoriasis. Dermatology 2002; 204(3):21421. [PUBMED: 12037450] van der Vleuten 1995 {published data only} van der Vleuten CJM, de Jong EMGJ, Rulo EHFC, Gerritsen MJP, Van de Kerkhof PCM. In-Patient Treatment with Calcipotriol Versus Dithranol in Refractory Psoriasis. European Journal of Dermatology 1995;5(8):6769. [EMBASE: 1996010645] Vanderploeg 1976 {published data only} Vanderploeg DE. Betamethasone Dipropionate Ointment in the Treatment of Psoriasis and Atopic Dermatitis: A Double-Blind Study. Southern Medical Journal 1976;69(7): 8623. [PUBMED: 781848] Veien 1997 {published and unpublished data} Veien NK, Bjerke JR, Rossmann-Ringdahl I, Jakobsen HB. Once daily treatment of psoriasis with tacalcitol compared with twice daily treatment with calcipotriol. A double-blind trial. British Journal Of Dermatology 1997;137(4):5816. [PUBMED: 9390335] Vladimirov 1994 {published data only} Vladimirov VV, Tcherjomukchina IG, Kurjanova ON, Menshikova LV, Mazina NM. Efcacy of calcipotriol
56
ointment compared to betamethasone 17-valerate ointment in the treatment of psoriasis. Skin Therapy Update. Crete, Greece, 1994:219. Volden 1992 {published data only} Volden G, Bjornberg A, Tegner E, Pedersen NB, Arles UB, Agren S, et al.Short-Contact Treatment at Home with Micanol. Acta Dermato Venereologica. Supplementum 1992; 172:202. [PUBMED: 1585757] Wall 1998 {published and unpublished data} Wall AR, Poyner TF. Psoriasis; the Burden of Disease Before, During and After Treatment with Dovonex Ointment or Dithrocream. British Journal Of Dermatology 1997;137 (Suppl 50):55. Wall ARJ, Poyner TF, Menday AP. A comparison of treatment with dithranol and calcipotriol on the clinical severity and quality of life in patients with psoriasis. British Journal Of Dermatology 1998;139(6):100511. [PUBMED: 9990363] Weinstein 1996 {published data only} Weinstein GD. Safety, Efcacy and Duration of Therapeutic Effect of Tazarotene Used in the Treatment of Plaque Psoriasis. British Journal Of Dermatology 1996;135(Suppl 49):326. [PUBMED: 9035703] Weinstein GD, Krueger GG, Lowe NJ, Duvic M, Friedman DJ, Jegasothy BV, et al.Tazarotene gel, a new retinoid, for topical therapy of psoriasis: vehicle-controlled study of safety, efcacy, and duration of therapeutic effect. Journal of the American Academy of Dermatology 1997;37(1): 8592. [PUBMED: 9216528] Weinstein 2003 {published data only} Weinstein GD. Tazarotene cream in the treatment of plaque psoriasis Abstract. 20th World Congress of Dermatology. 2002:P2043. Weinstein GD, Koo JY, Krueger GG, Lebwohl MG, Lowe NJ, Menter MA, et al.Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efcacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks. Journal of the American Academy of Dermatology 2003;48(5):7607. [PUBMED: 12734506] Wolska 1995 {published data only} Wolska H, Laws S, Schulz-Kiesow M, Grossman R, Jablonska S, Stadlers R, et al.Clinical evaluation of a PAFantagonist in psoriasis vulgaris. Journal Of Dermatological Treatment 1995;6(1):435. [EMBASE: 1995125049] Wortzel 1975 (1) {published data only} Wortzel MH. A new corticosteroid for moderate/severe dermatoses. Clinical medicine 1975;82(3):236. Wortzel 1975 (2) {published data only} Wortzel WH. A new corticosteroid for moderate/severe dermatoses. Clinical medicine 1975;82(3):236. Wozel 2001 {published and unpublished data} Wozel G. Treatment of chronic-stationary psoriasis with uocinolone acetonide and calcipotriol. (Ger.). Zeitschrift Fur Hautkrankheiten 2001;76(7-8):482.
Zonneveld 1998 (H) {published data only} Zonneveld IM, Rubins A, Jablonska S, Dobozy A, Ruzicka T, Kind P, et al.Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study. Archives of Dermatology 1998;134(9):11012. [PUBMED: 9762021] Zonneveld 1998 (P) {published data only} Zonneveld IM, Rubins A, Jablonska S, Dobozy A, Ruzicka T, Kind P, et al.Topical tacrolimus is not effective in chronic plaque psoriasis. A pilot study. Archives of Dermatology 1998;134(9):11012. [PUBMED: 9762021]
References to studies excluded from this review

Ambroziak 2002 {published data only} Ambroziak M, Stapor W, Langner A, Kwiek B. Clinical evaluation of the scalp psoriasis treatment with clobetasol propionate 0.05% lotion. [Polish]. Przeglad Dermatologiczny 2002;89(3):23740. Baadsgaard 1995 {published data only} Baadsgaard O, Traulsen J, Roed Petersen J, Jakobsen HB. Optimal concentration of tacalcitol in once-daily treatment of psoriasis. Journal Of Dermatological Treatment 1995;6(3): 14550. Baran 1999 {published data only} Baran R, Tosti A. Topical treatment of nail psoriasis with a new corticoid-containing nail lacquer formulation. Journal Of Dermatological Treatment 1999;10:2014. Bianchi 2003 {published data only} Bianchi L, Soda R, Diluvio L, Chimenti S. Tazarotene 0.1% gel for psoriasis of the ngernails and toenails: an open, prospective study. British Journal of Dermatology 2003;149 (1):2079. Callen 1996 {published data only} Callen J. Comparison of Safety and Efcacy of Fluticasone Propionate Cream, 0.05%, and Betamethasone Valerate Cream, 0.1%, in the Treatment of Moderate-to-Severe Psoriasis. Cutis 1996;57(2 Suppl):4550. Carroll 2005 {published data only} Carroll CL, Clarke J, Camacho F, Balkrishnan R, Feldman SR. Topical tacrolimus ointment combined with 6% salicylic acid gel for plaque psoriasis treatment. Archives of Dermatology 2005;141(1):436. De Jong 1999 {published and unpublished data} De Jong EM, Menke HE, Van Praag MC, Van De Kerkhof PC. Dystrophic psoriatic ngernails treated with 1% 5uorouracil in a nail penetration-enhancing vehicle: a double-blind study. Dermatology 1999;199(4):3138. Elias 1994 {published data only} Elias AN, Dangaran K, Barr RJ, Rohan MK, Goodman MM. A controlled trial of topical propylthiouracil in the treatment of patients with psoriasis. Journal of the American Academy of Dermatology 1994;31(3 Pt 1):4558. Jansen 1986 {published data only} Jansen C, Lammintausta K, Bullingham RES, Forsstrom S. A Clinical Trial of Lonapalene Fluocinolone Acetonide and
57
Vehicle in Psoriasis. Journal of Investigative Dermatology. Meeting Abstract 1986;86(4):483. Kragballe 1989 {published data only} Kragballe K. Treatment of psoriasis by the topical application of the novel cholecalciferol analogue calcipotriol (Mc 903). Archives of Dermatology 1989;125(12):164752. Kragballe 1994 {published data only} Kragballe K, Dam TN, Hansen ER, Baadsgaard O, Gronhoj Larsen F, Sondergaard J, et al.Efcacy and Safety of the 20Epi-Vitamin D3 Analogue Kh 1060 in the Topical Therapy of Psoriasis: Results of a Dose-Ranging Study. Acta Dermato Venereologica 1994;74(5):398402. Lebwohl 1998b {published data only} Lebwohl M, Yoles A, Lombardi K, Lou W. Calcipotriene Ointment and Halobetasol Ointment in the LongTerm Treatment of Psoriasis: Effects on the Duration of Improvement. Journal of the American Academy of Dermatology 1998;39(3):44750. Lebwohl 2001 {published data only} Lebwohl M, Lombardi K, Tan MH. Duration of improvement in psoriasis after treatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment: comparison of maintenance treatments. International Journal Of Dermatology 2001;40(1):646. [MEDLINE: 11277960] Levin 2003 {published data only} Levin C, Fiorentino DF, Vosganian G, Chon S, Kimball AB. The safety of topical cyclosporin A conjugate (CGC1072) in the treatment of mild to moderate psoriasis. Abstract 1201 International Investigative Dermatology. The 4th Joint Meeting of the ESDR, Japanese SID & SID, 30th April-4thMay 2003, Florida, USA. Journal of Investigative Dermatology 2003;121(1):201. Meyrat 1996 {published and unpublished data} Meyrat R, Muller I. Daivonex registered trade mark ointment twice a day versus Daivonex registered trade mark cream in the morning and Daivonex registered trade mark ointment in the evening. Ars Medici 1996;86(20):121820. Reygagne 2002a {published data only} Reygagne P, Diaconu J, Prs H, Ernst TM, Meyer KG, S.A.D A. Efcacy and safety comparison of clobetasol propionate shampoo, gel and vehicle in scalp psoriasis. 11th Congress of the European Academy of Dermatology and Venereology. 2002:P279. Ruzicka 2004 {published data only} Ruzicka T, Trompke C. [Treatment of scalp psoriasis. An effective and safe tacalcitol emulsion]. Hautarzt 2004;55 (2):16570. Sander 1998 {published data only} Sander P, Stucker M, Hermes N, Hoffmann K, Altmeyer P. Mometasone and calcipotriol optimise the initial therapeutic effect of dithranol on chronic plaque psoriasis [Mometason Und Calcipotriol Optimieren Den Therapeutischen Initialeffekt Von Dithranol Auf Die Chronisch Stationare Psoriasis (CSP)]. Hautarzt 1998;49(4):2914.
Sefton 1984 {published data only} Sefton J, Loder JS, Kyriakopoulos AA. Clinical Evaluation of Hydrocortisone Valerate 0.2% Ointment. Clinical Therapeutics 1984;6(3):28293. Sharma 2003 {published data only} Sharma V, Kaur I, Kumar B. Calcipotriol versus coal tar: a prospective randomized study in stable plaque psoriasis. International Journal of Dermatology 2003;42(10):8348. Syed 2001a {published data only} Syed TA, Qureshi ZA. Management of psoriasis of the scalp with methotrexate (0.25%) in an aerosolized spray gel. A placebo-controlled, double-blind study. Skin Pharmacology & Applied Skin Physiology 2001;14(3):167. Tokura 2004 {published data only} Tokura Y. Effectiveness of Combination between Diucortolone Valerate and Vitamin D3 Analogue in the Treatment of Psoriasis Vulgaris. [Japanese]. Nishinihon Journal of Dermatology 2004;66(2):188191. Tzaneva 2003 {published data only} Tzaneva S, Honigsmann H, Tanew A. Observer-blind, randomized, intrapatient comparison of a novel 1% coal tar preparation (Exorex) and calcipotriol cream in the treatment of plaque type psoriasis. British Journal of Dermatology 2003;149(2):3503. van de Kerkhof 1996b {published data only} van de Kerkhof PCM, Kuypers A. A randomised, double blind, left right study to compare hydrocortisone 17butyrate 0.1% emulsion with vehicle in the treatment of patients suffering from psoriasis vulgaris. 6th International Skin Symposium. Brussels, 1996; Vol. Poster P16.
References to studies awaiting assessment

Bernstein 2006 {published data only} Bernstein S, Donsky H, Gulliver W, Hamilton D, Nobel S, Norman R. Treatment of mild to moderate psoriasis with Relieva, a Mahonia aquifolium extract--a double-blind, placebo-controlled study. American Journal of Therapeutics 2006; Vol. 13, issue 2:1216. Beutner 2006 {published data only} Beutner K, Chakrabarty A. An intra-individual safety and efcacy comparison of clobetasol propionate 0.05% spray and its vehicle in the treatment of plaque psoriasis. Abstract P2858. American Academy of Dermatology 64th Annual Meeting March 3-7, 2006. Journal of the American Academy of Dermatology 2006; Vol. 54, issue 3 Suppl: AB212. Beutner 2006a {published data only} Beutner K, Chakrabarty A, Lemke S, Yu K. An intraindividual randomized safety and efcacy comparison of clobetasol propionate 0.05% spray and its vehicle in the treatment of plaque psoriasis. Journal of Drugs in Dermatology 2006; Vol. 5, issue 4:35760. Brown 2005 {published data only} Brown AC, Koett J, Johnson DW, Semaskvich NM, Holck P, Lally D, et al.Effectiveness of kukui nut oil as
58
a topical treatment for psoriasis. International Journal of Dermatology 2005; Vol. 44, issue 8:6847. Buckley 2008 {published data only} Buckley C, Hoffmann V, Shapiro J, Saari S, Cambazard F, Milsgaard M. Calcipotriol plus betamethasone dipropionate scalp formulation is effective and well tolerated in the treatment of scalp psoriasis: a phase II study. Dermatology 2008; Vol. 217, issue 2:10713. de Korte 2008 {published data only} de Korte J, van der Valk PG, Sprangers MA, Damstra RJ, Kunkeler AC, Lijnen RL, et al.A comparison of twice-daily calcipotriol ointment with once-daily shortcontact dithranol cream therapy: quality-of-life outcomes of a randomized controlled trial of supervised treatment of psoriasis in a day-care setting. British Journal of Dermatology 2008; Vol. 158, issue 2:37581. Friedrich 2004 {published data only} Friedrich M, Vollhardt K, Zahlten R, Sterry W, Wolff G. Demonstration of antipsoriatic efcacy of a new topical formulation of the small molecule selectin antagonist bimosiamose Abstract P016 European Congress on Psoriasis 2004. Journal of the European Academy of Dermatology & Venereology 2004; Vol. 18, issue 6:779. Gold 2006 {published data only} Gold LS. Correlation between amount of drug used versus efcacy of calcipotriene/betamethasone in severe psoriasis during a 52-week study. Abstract P2873. American Academy of Dermatology 64th Annual Meeting March 3-7, 2006. Journal of the American Academy of Dermatology 2006; Vol. 54, issue 3 Suppl:AB216. Gottschalk 2007 {published data only} Gottschalk RW, Johnson LA. Calcitriol 3 micrograms/g versus calcipotriol 50 micrograms/g for plaque psoriasis: treatment, maintenance and cost Abstract P2720. American Academy of Dermatology 65th Annual Meeting February 26, 2007. Journal of the American Academy of Dermatology 2007; Vol. 56, issue 2:AB179. Helfrich 2007 {published data only} Helfrich YR, Kang S, Hamilton TA, Voorhees JJ. Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study. British Journal of Dermatology 2007; Vol. 157, issue 2:36974. Jarratt 2006 {published data only} Jarratt MT, Clark SD, Savin RC, Swinyer LJ, Saey CF, Brodell RT, et al.Evaluation of the efcacy and safety of clobetasol propionate spray in the treatment of plaque-type psoriasis. Cutis 2006; Vol. 78, issue 5:34854. Jemec 2007 {published data only} Jemec GBE, Burden D, Poulin Y, Ortonne JP. A new scalp formulation of calcipotriene plus betamethasone in the treatment of scalp psoriasis compared to its active ingredients and the vehicle Abstract P2733. American Academy of Dermatology 65th Annual Meeting February 26, 2007. Journal of the American Academy of Dermatology 2007; Vol. 56, issue 2:AB182.
Jemec 2008 {published data only} Jemec GBE, Ganslandt C, Ortonne J-P, Poulin Y, Burden AD, de Unamuno P, et al.A new scalp formulation of calcipotriene plus betamethasone compared with its active ingredients and the vehicle in the treatment of scalp psoriasis: a randomized, double-blind, controlled trial. Journal of the American Academy of Dermatology 2008; Vol. 59, issue 3:45563. Ji 2008 {published data only} Ji S, Chen X, Wang B, Jin H, Zhao G, Wang Y, Chen Z, Liu X, Gu J, Guo Z, Zhu X. Calcitriol ointment versus calcipotriol ointment in the treatment of psoriasis: a singleblind, randomized, multicenter trial (Chinese). Zhonghua Pifuke Zazhi 2008; Vol. 41, issue 3:153156. [: BIOSIS] Jorizzo 2007 {published data only} Jorizzo J. Efcacy with calcipotriene and betamethasone dipropionate ointment in patients with moderate and severe psoriasis Abstract P2780. American Academy of Dermatology 65th Annual Meeting February 2-6, 2007. Journal of the American Academy of Dermatology 2007; Vol. 56, issue 2:AB194. Kaur 2004 {published data only} Kaur I, Jain R, Kumar B. Comparative study of calcipotriol (0.005%) vs tazarotene (0.05%, 0.1%) in stable plaque psoriasis. Abstract P015 European Congress on Psoriasis 2004. Journal of the European Academy of Dermatology & Venereology 2004; Vol. 18, issue 6:779. Koo 2006 {published data only} Koo J, Blum RR, Lebwohl M. A randomized, multicenter study of calcipotriene ointment and clobetasol propionate foam in the sequential treatment of localized plaque-type psoriasis: short- and long-term outcomes. Journal of the American Academy of Dermatology 2006; Vol. 55, issue 4: 63741. Kragballe 2006 {published data only} Kragballe K, Bibby A. Long-term efcacy of a calcipotriene/ betamethasone dipropionate two compound product in Psoriasis vulgaris. Abstract P2891. American Academy of Dermatology 64th Annual Meeting March 3-7, 2006. Journal of the American Academy of Dermatology 2006; Vol. 54, issue 3 Suppl:AB220. Kragballe 2006a {published data only} Kragballe K, Austad J, Barnes L, Bibby A, de la Brassinne M, Cambazard F, et al.A 52-week randomized safety study of a calcipotriol/betamethasone dipropionate two-compound product (Dovobet/Daivobet/Taclonex) in the treatment of psoriasis vulgaris. British Journal of Dermatology 2006; Vol. 154, issue 6:115560. Kragballe 2006b {published data only} Kragballe K, Austad J, Barnes L, Bibby A, de la Brassinne M, Cambazard F, et al.Efcacy results of a 52-week, randomised, double-blind, safety study of a calcipotriol/ betamethasone dipropionate two-compound product (Daivobet/Dovobet/Taclonex) in the treatment of psoriasis vulgaris. Dermatology 2006; Vol. 213, issue 4:31926.
59
Kreuter 2006 {published data only} Kreuter A, Sommer A, Hyun J, Brautigam M, Brockmeyer NH, Altmeyer P, et al.1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone in the treatment of intertriginous psoriasis: a double-blind, randomized controlled study. Archives of Dermatology 2006; Vol. 142, issue 9:113843. Lebwohl 2007 {published data only} Lebwohl M, Menter A, Weiss J, Clark SD, Flores J, Powers J, et al.Calcitriol 3 microg/g ointment in the management of mild to moderate plaque type psoriasis: results from 2 placebo-controlled, multicenter, randomized double-blind, clinical studies. Journal of Drugs in Dermatology: JDD 2007; Vol. 6, issue 4:42835. Lee 2007 {published data only} Lee J, Youn J, Kim N, Kim K, Kim T, Choi J, et al.A randomized investigator-blinded comparative study of calcitriol twice a day vs. diucortolone valerate morning plus calcitriol evening application in the treatment of mild to moderate psoriasis. Journal of the European Academy of Dermatology and Venereology 2007; Vol. 21, issue Suppl. 1:19. Liao 2007 {published data only} Liao YH, Chiu HC, Tseng YS, Tsai TF. Comparison of cutaneous tolerance and efcacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial. British Journal of Dermatology 2007; Vol. 157, issue 5:100512. Lowe 2005 {published data only} Lowe N, Feldman SR, Sherer D, Weiss J, Shavin JS, Lin YL, et al.Clobetasol propionate lotion, an efcient and safe alternative to clobetasol propionate emollient cream in subjects with moderate to severe plaque-type psoriasis. Journal of Dermatological Treatment 2005; Vol. 16, issue 3:15864. Luger 2008 {published data only} Luger T, Kidson P, Cambazard F, Larsen FG. A 1-year, randomized, double-blind safety study of long-term treatment of a new gel formulation containing calcipotriene plus betamethasone dipropionate in scalp psoriasis. Journal of the American Academy of Dermatology 2008; Vol. 58, issue 2:AB134. Luger 2008a {published data only} Luger TA, Cambazard F, Larsen FG, Bourcier M, Gupta G, Clonier F, et al.A Study of the Safety and Efcacy of Calcipotriol and Betamethasone Dipropionate Scalp Formulation in the Long-Term Management of Scalp Psoriasis. Dermatology 2008; Vol. 217, issue 4:3218. Maier 2004 {published data only} Maier H. Prospective, randomized controlled double-blind study on the efcacy and safety of a series of herbal skincare products for stable chronic plaque psoriasis. Abstract P061 European Congress on Psoriasis 2004. Journal of the European Academy of Dermatology & Venereology 2004; Vol. 18, issue 6:794.
Menter 2008 {published data only} Menter A, Colon L, Johnson L, Gottschalk R. Results from a randomized study comparing clobetasol propionate 0.05% spray to calcipotriene 0.005%, betamethasone dipropionate 0.064% ointment for the treatment of plaque psoriasis. Journal of the American Academy of Dermatology 2008; Vol. 58, issue 2:AB124. Ortonne 2006 {published data only} Ortonne J-P, van de Kerkhof PCM, Prinz JC, Bieber T, Lahfa M, Rubins A, et al.0.3% Tacrolimus gel and 0.5% Tacrolimus cream show efcacy in mild to moderate plaque psoriasis: Results of a randomized, open-label, observerblinded study. Acta Dermato-Venereologica 2006; Vol. 86, issue 1:2933. Powers 2005 {published data only} Powers J, Balin AK, Kempers S, Glinert RJ, Fleming T, Graeber M. Assessment of the efcacy and safety of calcitriol 3ugg-1 ointment in the treatment of chronic plaque psoriasis. Abstract P-40 The 85th BAD Annual Meeting 5-8th July 2005, Glasgow, UK. British Journal of Dermatology 2005; Vol. 153, issue Suppl 1:32. Powers 2005a {published data only} Powers J. Assessment of the Efcacy and Safety of Calcitriol 3mcg/g Ointment in the Treatment of Chronic Plaque Psoriasis. 7th Asian Congress of Dermatology incorporating the 5th Regional Conference of Paediatric Dermatology Kuala Lumpur, Malaysia 28th September -1st October, 2005 2005:367. Reygagne 2005 {published data only} Reygagne P, Mrowietz U, Decroix J, De Waard-Van Der Spek FB, Acebes LO, Figueiredo A, et al.Clobetasol propionate shampoo 0.05% and calcipotriol solution 0.005%: A randomized comparison of efcacy and safety in subjects with scalp psoriasis. Journal of Dermatological Treatment 2005; Vol. 16, issue 1:316. Saraceno 2007 {published data only} Saraceno R, Andreassi L, Ayala F, Bongiorno MR, Giannetti A, Lisi P, et al.Efcacy, safety and quality of life of calcipotriol/betamethasone dipropionate (Dovobet) versus calcipotriol (Daivonex) in the treatment of psoriasis vulgaris: a randomized, multicentre, clinical trial. Journal of Dermatological Treatment 2007; Vol. 18, issue 6:3615. Saraswat 2007 {published data only} Saraswat A, Agarwal R, Katare OP, Kaur I, Kumar B. A randomized, double-blind, vehicle-controlled study of a novel liposomal dithranol formulation in psoriasis. Journal of Dermatological Treatment 2007; Vol. 18, issue 1:405. van de Kerkhof 2005 {published data only} Van De Kerkhof PCM. Once daily vs. twice daily applications of topical treatments in psoriasis [15]. British Journal of Dermatology 2005; Vol. 153, issue 6:1245. van de Kerkhof 2006 {published data only} van de Kerkhof PC, van der Valk PG, Swinkels OQ, Kucharekova M, de Rie MA, de Vries HJ, et al.A comparison of twice-daily calcipotriol ointment with once-daily shortcontact dithranol cream therapy: a randomized controlled
60
trial of supervised treatment of psoriasis vulgaris in a daycare setting. British Journal of Dermatology 2006; Vol. 155, issue 4:8007. van de Kerkhof 2007 {published data only} van de Kerkhof P, Anstey A, Barnes L, Bolduc C. A new scalp formulation of calcipotriene plus betamethasone in the treatment of scalp psoriasis compared to its active ingredients in the same vehicle Abstract P2734. American Academy of Dermatology 65th Annual Meeting February 26, 2007. Journal of the American Academy of Dermatology 2007; Vol. 56, issue 2:AB182. White 2006 {published data only} White S, Vender R, Thaci D, Haverkamp C, Naeyaert J-M, Foster R, et al.Use of calcipotriene cream (Dovonex cream) following acute treatment of psoriasis vulgaris with the calcipotriene/betamethasone dipropionate two-compound product (Taclonex): a randomized, parallel-group clinical trial. American Journal of Clinical Dermatology 2006; Vol. 7, issue 3:17784. Xuejun 2005 {published data only} Xuejun Z, Baoxi W, Guang Z, Jun G, Zhiqiang C, Briantais P, et al.A comparison of the efcacy and safety of twice daily applications of calcitriol 3 lg/g ointment versus calcipotriol 50 mcg/g ointment in subjects with mild to moderate chronic plaque-type psoriasis. Abstract P0647. The 14th Congress of the European Academy of Dermatology and Venereology, London, UK. 12-15th October 2005. Journal of the European Academy of Dermatology & Venereology 2005; Vol. 19, issue Suppl 2:172. Zhu 2007 {published data only} Zhu X, Wang B, Zhao G, Gu J, Chen Z, Briantais P, et al.An investigator-masked comparison of the efcacy and safety of twice daily applications of calcitriol 3 microg/g ointment vs. calcipotriol 50 microg/g ointment in subjects with mild to moderate chronic plaque-type psoriasis. Journal of the European Academy of Dermatology & Venereology 2007; Vol. 21, issue 4:46672.
Fleming 2008 {unpublished data only} Efcacy and Safety of Calcipotriol Plus Hydrocortisone Ointment Compared With Tacalcitol Ointment in Patients With Psoriasis on the Face and Skin Folds. Ongoing study February 2008. Gottschalk {unpublished data only} Efcacy, Safety, Preference and Response Duration of Clobex Spray and Taclonex Ointment in Psoriasis. Ongoing study August 2006. Hoffmann {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel Compared With Tacalcitol Ointment and the Gel Vehicle Alone in Patients With Psoriasis Vulgaris. Ongoing study April 2008. Holick {unpublished data only} Treatment of Psoriasis With Parathyroid Hormone. Ongoing study January 2000. Jemec {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Gel in the Treatment of Scalp Psoriasis. Ongoing study November 2004. Kimball {unpublished data only} LCD Solution Versus Calcipotriol Cream in the Treatment of Moderate Plaque Psoriasis. Ongoing study January 2007. Kragballe {unpublished data only} Efcacy of Calcipotriol Plus Betamethasone Gel Versus Calcipotriol Scalp Solution in Scalp Psoriasis. Ongoing study May 2006. Luger {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel for up to a Year in Scalp Psoriasis. Ongoing study February 2005. Lukic {unpublished data only} A Safety and Efcacy Study of a Topical Gel for the Treatment of Mild to Moderate Psoriasis. Ongoing study October 2007. Poulin {unpublished data only} Maintenance Effect of Clobex Shampoo on Subjects With Moderate to Severe Scalp Psoriasis. Ongoing study September 2006. QuatRx {unpublished data only} Safety and Efcacy Study of Two Dose Regimens of Becocalcidiol in the Treatment of Plaque-Type Psoriasis. Ongoing study September 2004. Theobald {unpublished data only} Study of Dose-Effect of COL-121 Ointment in Patients With Plaque-Type Psoriasis. Ongoing study January 2008. van de Kerkhof {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel in Scalp Psoriasis. Ongoing study December 2004. White {unpublished data only} Efcacy and Safety of Calcipotriol Cream and (Calcipotriol + Betamethasone Dipropionate) Ointment in Psoriasis Vulgaris. Ongoing study April 2005.
61
References to ongoing studies

Altmeyer {unpublished data only} Topical Vitamin B12 in Chronic Plaque Psoriasis. Ongoing study January 2001. Angulo {unpublished data only} Study to Compare U0267 Foam Against Vehicle Foam in Subjects With Plaque-Type Psoriasis. Ongoing study April 2008. Bibby {unpublished data only} Efcacy and safety of calcipotriene / Betamethasone Gel / Ointment in Psoriasis. Ongoing study Octrober 2006. Cytochroma {unpublished data only} Safety and Efcacy of Topically Applied CTA018 in Plaque Psoriasis. Ongoing study September 2006. Fleming 2006 {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel in Psoriasis Vulgaris. Ongoing study December 2005.
Wozel {unpublished data only} Evaluation of Topical Antipsoriatics in the Psoriasis Plaque Test. Ongoing study September 2004. Yin-ku Lin {unpublished data only} Randomised, observer-blinded, vehicle-controlled trial on the efcacy and safety of a topical indigo naturalise ointment treatment for recalcitrant psoriasis vulgaris. Ongoing study 01/05/2004. Zheng {unpublished data only} Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Ointment in Patients With Psoriasis Vulgaris. Ongoing study October 2005.
of dermatology. Acta Dermato-Venereologica. Supplementum. 1994;186:1078. Barker 1991 Barker JN. The pathophysiology of psoriasis. Lancet 1991; 338(8761):22730. Barnes 2000 Barnes L, Altmeyer P, Forstrom L, Stenstrom MH. Longterm treatment of psoriasis with calcipotriol scalp solution and cream. European Journal of Dermatology 2000;10(3): 199204. Berth Jones 1992c Berth Jones. Immediate and long term effects of topical calcipotriol on calcium homeostatis during treatment of psoriasis. Abstract. British Journal of Dermatology. 1992; Vol. 127, issue Suppl 40:17. Berth-Jones 1993 Berth-Jones J, Bourke JF, Iqbal SJ, Hutchinson PE. Urine Calcium Excretion During Treatment of Psoriasis with Topical Calcipotriol. British Journal Of Dermatology 1993; 129(4):4114. Bhalerao 1998 Bhalerao J, Bowcock AM. The genetics of psoriasis: a complex disorder of the skin and immune system. Human Molecular Genetics 1998;7(10):153745. Bleiker 1998 Bleiker TO, Bourke JF, Mumford R, Hutchinson PE. Long-Term Outcome of Severe Chronic Plaque Psoriasis Following Treatment with High-Dose Topical Calcipotriol. British Journal Of Dermatology 1998;139(2):2856. BMA 2007 British Medical Association, Royal Pharmaceutical Society of Great Britain. British National Formulary No. 54. London: BMJ Books, 2007. Bonifati 1998 Bonifati C, Carducci M, Mussi A, DAuria L, Ameglio F. Recognition and treatment of psoriasis: special considerations in elderly patients. Drugs & Aging 1998;12 (3):17790. Bos 2002 Bos JD. Topical tacrolimus and pimecrolimus are not associated with skin atrophy. British Journal of Dermatology 2002;146(2):342. Bos 2008 Bos JD, Spuls PI. Topical treatments in psoriasis: today and tomorrow. Clinics in Dermatology. Elsevier Inc 2008; Vol. 26, issue 5:4327. Bourke 1993a Bourke JF, Berth-Jones J, Iqbal SJ, Hutchinson PE. Highdose topical calcipotriol in the treatment of extensive psoriasis vulgaris. British Journal of Dermatology 1993;129 (1):746. Bourke 1994 Bourke JF, Berth-Jones J, Mumford R, Iqbal SJ, Hutchinson PE. High dose topical calcipotriol consistently reduces
62
Additional references
A 2005 A T, de Gannes G, Huang C, Zhou Y. Topical therapies for psoriasis: evidence-based review. Canadian Family Physician 2005; Vol. 51:51925. Angus 2006 Angus JE, Andriolo RB, Bigby M, Goodman SN, Jobling R, Williams HC. Biologics for chronic plaque psoriasis (Protocol). Cochrane Database of Systematic Reviews 2006, issue 4:Art. No.: CD006138. DOI: 10.1002/ 14651858.CD006138.pub2. Ashcroft 2000 Ashcroft DM, Li Wan Po A, Williams HC, Grifths CE. Cost-effectiveness analysis of topical calcipotriol versus short-contact dithranol in the treatment of mild to moderate plaque psoriasis. Pharmacoeconomics 2000;18(5):46976. Ashcroft 2000a Ashcroft DM, Po AL, Williams HC, Grifths CE. Systematic review of comparative efcacy and tolerability of calcipotriol in treating chronic plaque psoriasis. BMJ 2000; Vol. 320, issue 7240:9637. Aste 2004 Aste N. Tacalcitol ointment in the treatment of psoriasis. Giornale Italiano di Dermatologia e Venereologia 2004;139 (1):814. Atkinson 2004 Atkinson MJ, Sinha A, Hass SL, Colman SS, Kumar RN, Brod M, et al.Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health & Quality of Life Outcomes 2004;2 (1):12. Balkrishnan 2003 Balkrishnan R, Carroll CL, Camacho FT, Feldman SR. Electronic monitoring of medication adherence in skin disease: Results of a pilot study. Journal of the American Academy of Dermatology 2003;49(4):6514. Barisic-Drusko 1994 Barisic-Drusko V, Dobric I, Pasic A, Paljan D, Jukic Z, Basta-Juzbasic A, et al.Frequency of psoriatic arthritis in general population and among the psoriatics in department
serum parathyroid hormone levels. Clinical Endocrinology 1994;41(3):2957. Brandrup 1978 Brandrup F, Hauge M, Henningsen K, Eriksen B. Psoriasis in an unselected series of twins. Archives of Dermatology 1978;114(6):8748. Brownell 2007 Brownell I, Strober BE. Folate with methotrexate: big benet, questionable cost. British Journal of Dermatology 2007; Vol. 157, issue 1:213. Bruner 2003a Bruner CR, Feldman SR, Ventrapragada M, Fleischer AB, Jr. A systematic review of adverse effects associated with topical treatments for psoriasis. Dermatology Online Journal. 2003; Vol. 9, issue 1:2. Camp 1992 Camp RDR. Psoriasis. In: Champion RH, Burton JL, Ebling FJG editor(s). Textbook of Dermatology. Oxford: Blackwell Science, 1992:1391458. Carey 2006 Carey W, Glazer S, Gottlieb AB, Lebwohl M, Leonardi C, Menter A, et al.Relapse, rebound, and psoriasis adverse events: an advisory group report. Journal of the American Academy of Dermatology 2006; Vol. 54, issue 4 Suppl 1: S17181. Carroll 2004a Carroll CL, Feldman SR, Camacho FT, Balkrishnan R. Better medication adherence results in greater improvement in severity of psoriasis. British Journal of Dermatology 2004; 151(4):8957. Carroll 2004b Carroll CL, Feldman SR, Camacho FT, Manuel JC, Balkrishnan R. Adherence to topical therapy decreases during the course of an 8-week psoriasis clinical trial: commonly used methods of measuring adherence to topical therapy overestimate actual use. Journal of the American Academy of Dermatology 2004;51(2):2126. Chalmers 2000 Chalmers RJ, OSullivan T, Owen CM, Grifths CE. Interventions for guttate psoriasis. Cochrane Database of Systematic Reviews 2000; Vol. 2. [MEDLINE: Review] Chalmers 2006 Chalmers RJG, Hollis S, Leonardi-Bee J, Grifths CEM, Marsland AM. Interventions for chronic palmoplantar pustulosis. Cochrane Database of Systematic Reviews 2006, issue 1:CD001433. Chu 2000 Chu T. Better patient compliance in psoriasis. Practitioner 2000;244(1608):23842. Corbett 1976 Corbett MF. The response of psoriasis to betamethasone valerate and clobetasol propionate: a 6-month controlled study. British Journal Of Dermatology 1976;12:8993. Cork 2003 Cork MJ, Britton J, Butler L, Young S, Murphy R, Keohane SG. Comparison of parent knowledge, therapy utilization
and severity of atopic eczema before and after explanation and demonstration of topical therapies by a specialist dermatology nurse. British Journal of Dermatology 2003; 149(3):5829. Cullen 1996 Cullen SI. Long-Term Effectiveness and Safety of Topical Calcipotriene for Psoriasis. Calcipotriene Study Group. Southern Medical Journal 1996;89(11):10536. de Jong 1997 de Jong EM. The course of psoriasis. Clinics in Dermatology 1997;15(5):68792. de Tiedra 1997 De Tiedra A, Mercadal J, Lozano R. Prednicarbate versus uocortin for inammatory dermatoses. A cost-effectiveness study. Pharmacoeconomics 1997;12(2 Pt 1):193208. du Vivier 1975 du Vivier A, Stoughton RB. Tachyphylaxis to the action of topically applied corticosteroids. Archives of Dermatology 1975;111(5):5813. Farber 1974 Farber EM, Nall ML, Watson W. Natural history of psoriasis in 61 twin pairs. Archives of Dermatology 1974;109 (2):20711. Feldman 1997 Feldman SR, Fleischer AB, Jr, Reboussin DM, Rapp SR, Bradham DD, Exum ML, et al.The economic impact of psoriasis increases with psoriasis severity. Journal of the American Academy of Dermatology 1997;37(4):5649. Feldman 2000 Feldman SR, Sahu S, Fleischer AB, Jr, Dezii CM. Per-gram cost of medication is by itself a poor indicator for comparing costs of different psoriasis treatments: a retrospective cohort study of the cost of psoriasis treatment with topical corticosteroids versus topical calcipotriene. Journal of Cutaneous Medicine & Surgery 2000;4(3):1215. Feldman 2007 Feldman SR, Camacho FT, Krejci-Manwaring J, Carroll CL, Balkrishnan R. Adherence to topical therapy increases around the time of ofce visits. Journal of the American Academy of Dermatology 2007;57(1):813. Ferrandiz 1998 Ferrandiz C, Bielsa I, Ribera M, Fuente MJ, Carrascosa JM. Reinforcement Therapy in Patients with Psoriasis Treated with Calcipotriol Cream Terapia De Refuerzo En Pacientes Con Psoriasis Tratada Con Calcipotriol. Actas Dermo Siliogracas 1998;89(11):626630. Finlay 1994 Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - a simple practical measure for routine clinical use. Clinical & Experimental Dermatology 1994;19(3):21016. Finlay 1995a Finlay AY, Coles EC. The effect of severe psoriasis on the quality of life of 369 patients. British Journal of Dermatology 1995;132(2):23644.
63
Finlay 1995b Finlay AY. Coping with psoriasis. BMJ 1995;310(6995): 1673. Finlay 2001 Finlay AY. Psoriasis from the patients point of view. Archives of Dermatology 2001;137(3):3523. Finlay 2005 Finlay AY. Current severe psoriasis and the rule of tens. British Journal of Dermatology 2005;152(5):8617. Floden 1975 Floden C, Woodbridge P, Samman P, Kurwa AR. Comparison of the Response of Psoriasis, over a 6Month Period, to Clobetasol Propionate and Fluocinolone Acetonide Ointments. Current Medical Research & Opinion 1975;3(6):37581. Fluhr 2008 Fluhr JW, Cavallotti C, Berardesca E. Emollients, moisturizers, and keratolytic agents in psoriasis. Clinics in Dermatology 2008; Vol. 26, issue 4:3806. Fortune 2003 Fortune DG, Richards HL, Kirby B, McElhone K, Markham T, Rogers S, et al.Psychological distress impairs clearance of psoriasis in patients treated with photochemotherapy. Archives of Dermatology 2003;139(6): 7526. Fouere 2005 Fouere S, Adjadj L, Pawin H. How patients experience psoriasis: results from a European survey. Journal of the European Academy of Dermatology & Venereology 2005;19 Suppl 3:26. Franssen 1999 Franssen ME, van der Wilt GJ, de Jong PC, Bos RP, Arnold WP. A retrospective study of the teratogenicity of dermatological coal tar products. Acta DermatoVenereologica 1999;79(5):3901. Fredriksson 1980 Fredriksson T, Lassus A, Bleeker J. Treatment of psoriasis and atopic dermatitis with halcinonide cream applied once and three times daily. British Journal of Dermatology 1980; 102(5):5757. Gerritsen 2001 Gerritsen MJ, Van De Kerkhof PC, Langner A. Long-term safety of topical calcitriol 3 microg g(-1) ointment. British Journal Of Dermatology 2001;144(Suppl 58):179. Ghoreschi 2007 Ghoreschi K, Weigert C, Rocken M. Immunopathogenesis and role of T cells in psoriasis. Clinics in Dermatology 2007; Vol. 25, issue 6:57480. Goeckerman 1931 Goeckerman WH. Treatment of psoriasis. A. M. A. archives of dermatology and syphilology 1931;24:44650. Gokdemir 2008 Gokdemir G, Ari S, Ksl A. Adherence to treatment in patients with psoriasis vulgaris: Turkish experience. Journal
of the European Academy of Dermatology and Venereology 2008;22(3):3305. Grifths 2003 Grifths CEM. The immunological basis of psoriasis. Journal of the European Academy of Dermatology & Venereology 2003;17(s2):15. Grifths 2004 Grifths CEM. Psoriasis: future research needs and goals for the twenty-rst century. Dermatologic Clinics 2004; Vol. 22, issue 4:4939. Grifths 2007 Grifths CEM, Christophers E, Barker JNWN, Chalmers RJG, Chimenti S, Krueger GG, et al.A classication of psoriasis vulgaris according to phenotype. British Journal of Dermatology 2007; Vol. 156, issue 2:25862. Grifths 2007a Grifths CEM, Barker JNWN. Pathogenesis and clinical features of psoriasis. Lancet 2007; Vol. 370, issue 9583: 26371. Gupta 1998 Gupta MA, Gupta AK, Watteel GN. Perceived deprivation of social touch in psoriasis is associated with greater psychologic morbidity: an index of the stigma experience in dermatologic disorders. Cutis; cutaneous medicine for the practitioner 1998;61(6):33942. Gupta 2007 Gupta G, Bhattacharya S. Psoriasis: maximizing topical treatment concordance. British Journal of Hospital Medicine 2007;68(5):2636. Guzzo 1996 Guzzo C, Lazarus G, Goffe BS, Katz HI, Lowe NJ, Pincus SH. Topical Calcipotriene Has No Short-Term Effect on Calcium and Bone Metabolism of Patients with Psoriasis. Journal of the American Academy of Dermatology 1996;34(3): 42933. Harries 2005 Harries M, Ball DFJ, Mrowietz U, Chalmers R, Grifths CEM. Fumaric acid esters for psoriasis (Protocol). Cochrane Database of Systematic Reviews 2005, issue 4:Art. No.: CD005499. DOI: 10.1002/14651858.CD005499. Harries 2005a Harries M, Butterworth A, Grifths CEM, Chalmers R. Methotrexate for psoriasis (Protocol). Cochrane Database of Systematic Reviews 2005, Issue 2.. Cochrane Database of Systematic Reviews 2005, issue 2:Art. No.: CD005204. DOI: 10.1002/14651858.CD005204. Harrington 1995 Harrington CI. Cost-Effectiveness Analysis of Calcipotriol Ointment and Short-Contact Dithranol in Treating Mildto-Moderate Psoriasis. British Journal Of Medical Economics 1995;8(1):2732. Hellgren 1967 Hellgren L. Psoriasis. The prevalence in sex, age and occupational groups in total populations in Sweden: morphology, inheritance and association with other skin and rheumatic diseases. Stockholm: Almqvist & Wiksell, 1967.
64
Heng 1990 Heng MC, Heng Hl, Allen SG. Basement Membrane Changes in Psoriatic Patients on Long-Term Topical Corticosteroid Therapy. Clinical & Experimental Dermatology 1990;15(2):8390. Hengge 2006 Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. Journal of the American Academy of Dermatology 2006;54(1):1-15; quiz 16-8. Henseler 1992 Henseler T, Koch F, Westphal E, Nair RP, Vorhees JJ, Elder JT, et al.Presence of HLA-DR7 in type-I-psoriasis. Clinical Research 1992;40:A457. Higgins 2008 Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration. Available from www.cochrane-handbook.org, 2008. Holick 1996 Holick MF, Chen ML, Kong XF, Sanan DK. Clinical uses for calciotropic hormones 1, 25-dihydroxyvitamin D3 and parathyroid hormone-related peptide in dermatology: a new perspective. Journal of Investigative Dermatology. Symposium Proceedings 1996;1(1):19. Ingram 1953 Ingram JT. The approach to psoriasis. BMJ 1953;ii:5914. Janjua 2006 Janjua A, Chalmers R, Zheng A, Xiang Y, Harries M, Grifths CEM, et al.Oral retinoids for psoriasis (Protocol). Cochrane Database of Systematic Reviews 2006, issue 3:Art. No.: CD006139. DOI: 10.1002/14651858.CD006139. Jenner 2002 Jenner N, Campbell J, Plunkett A, Marks R. Cost of psoriasis: a study on the morbidity and nancial effects of having psoriasis in Australia. Australasian Journal of Dermatology 2002;43(4):25561. Juni 2001 Juni P, Altman DG, Egger M. Systematic reviews in health care: assessing the quality of controlled clinical trials. BMJ 2001;323(7303):426. Kao 2003 Kao JS, Fluhr JW, Man MQ, Fowler AJ, Hachem JP, Crumrine D, et al.Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities. Journal of Investigative Dermatology 2003; Vol. 120, issue 3:45664. Katz 1987b Katz HI, Hien NT, Prawer SE, Mastbaum LI, Mooney JJ, Samson CR. Superpotent Topical Steroid Treatment of Psoriasis Vulgaris--Clinical Efcacy and Adrenal Function. Journal of the American Academy of Dermatology 1987;16(4): 80411.
Katz 1989 Katz HI, Prawer SE, Mooney JJ, Samson CR. Preatrophy: Covert Sign of Thinned Skin. Journal of the American Academy of Dermatology 1989;20(5 Pt 1):7315. Kragballe 1988 Kragballe K, Beck HI, Sgaard H. Improvement of psoriasis by a topical vitamin D3 analogue (Mc 903) in a doubleblind study. British Journal of Dermatology 1988;119(2): 223230. Kragballe 1991b Kragballe K, Fogh K, Sogaard H. Long-Term Efcacy and Tolerability of Topical Calcipotriol in Psoriasis. Results of an Open Study. Acta Dermato Venereologica 1991;71(6): 4758. Krueger 1984 Krueger GG, Bergstresser PR, Lowe NJ, Voorhees JJ, Weinstein GD. Psoriasis. Journal of the American Academy of Dermatology 1984;11(5 Pt 2):93747. Krueger 2000 Krueger GG, Feldman SR, Camisa C, Duvic M, Elder JT, Gottlieb AB, et al.Two considerations for patients with psoriasis and their clinicians: what denes mild, moderate, and severe psoriasis? What constitutes a clinically signicant improvement when treating psoriasis?. Journal of the American Academy of Dermatology 2000;43(2 Pt 1):2815. Lambert 1996 Lambert J. Economic Analyses of the Treatment of Psoriasis. European Journal of Dermatology 1996;6(8):5437. Lambert 1999 Lambert J. Cost-Effectiveness of Treatments in Psoriasis. Journal Of Dermatological Treatment 1999;1:S9S13. Lambert 2002 Lambert J, Trompke C. Tacalcitol ointment for longterm control of chronic plaque psoriasis in dermatological practice. Dermatology 2002;204(4):3214. Langner 1996 Langner A, Ashton P, Van De Kerkhof PC, Verjans H. A long-term multicentre assessment of the safety and tolerability of calcitriol ointment in the treatment of chronic plaque psoriasis. British Journal of Dermatology 1996;135 (3):3859. Lebwohl 1996 Lebwohl M, Siskin SB, Epinette WW, Breneman D, Funicella T, Kalb RE, et al.A Multicenter Trial of Calcipotriene Ointment and Halobetasol Ointment Compared with Either Agent Alone for the Treatment of Psoriasis. Journal of the American Academy of Dermatology 1996;35:2689. Lee 1990 Lee FI, Bellary SV, Francis C. Increased occurrence of psoriasis in patients with Crohns disease and their relatives [comment]. American Journal of Gastroenterology 1990;85 (8):9623.
65
Lee 1998 Lee JY, Maibach HI. Corticosteroid skin atrophogenicity: assessment methods. Skin Research & Technology 1998;4(4): 1616. Lee 2006 Lee IA, Maibach HI. Pharmionics in dermatology: a review of topical medication adherence. American Journal of Clinical Dermatology 2006;7(4):2316. Leu 1985 Leu RE. Economic Evaluation of New Drug Therapies in Terms of Improved Life Quality. Social Science & Medicine 1985;21(10):115361. Lomholt 1963 Lomholt G. In: G L editor(s). Psoriasis, prevalence, spontaneous course and genetics. Published Ph.D Thesis. Copenhagen: G.E.C. Gad, 1963:313. Lundberg 1999 Lundberg L, Johannesson M, Silverdahl M, Hermansson C, Lindberg M. Quality of life, health-state utilities and willingness to pay in patients with psoriasis and atopic eczema. British Journal of Dermatology. 1999;141(6): 106775. Marchetti 1998 Marchetti ALKAP. A Pharmacoeconomic Analysis of Topical Therapies for Patients with Mild-to-Moderate Stable Plaque Psoriasis: A Us Study. Clinical Therapeutics 1998;20(4):85169. Mason (unpublished) Mason JM, Mason AR, Cork MJ. Topical Treatments for Psoriasis in Primary Care. Unpublished data. Mason 2002a Mason J, Mason AR, Cork MJ. Topical preparations for the treatment of psoriasis: a systematic review. British Journal Of Dermatology 2002;146(3):35164. Mason 2002b Mason J, Mason A, Cork M. Topical preparations for the treatment of psoriasis in primary care: a systematic review. University of York (OP41). York: University of York, 2002. Matthews 1996 Matthews D, Fry L, Powles A, Weber J, McCarthy M, Fisher E, et al.Evidence that a locus for familial psoriasis maps to chromosome 4q. Nature Genetics 1996;14(2):2313. McKenna 2003 McKenna SP, Cook SA, Whalley D, Doward LC, Richards HL, Grifths CE, et al.Development of the PSORIQoL, a psoriasis-specic measure of quality of life designed for use in clinical practice and trials. British Journal of Dermatology 2003;149(2):32331. Mee 1998 Mee JB, Cork MJ. Vitamin D receptor polymorphism and calcipotriol response in patients with psoriasis. Journal of Investigative Dermatology 1998;110(3):3012. Miyachi 2002 Miyachi Y, Ohkawara A, Ohkido M, Harada S, Tamaki K, Nakagawa H, et al.Long-term safety and efcacy of high-
concentration (20 microg/g) tacalcitol ointment in psoriasis vulgaris. European Journal of Dermatology 2002;12(5): 4638. Mortensen 1993 Mortensen L, Kragballe K, Wegmann E, Schifter S, Risteli J, Charles P. Treatment of psoriasis vulgaris with topical calcipotriol has no short-term effect on calcium or bone metabolism. A randomized, double-blind, placebocontrolled study. Acta Dermato-Venereologica 1993;73(4): 3004. Nair 1997 Nair RP, Henseler T, Jenisch S, Stuart P, Bichakjian CK, Lenk W, et al.Evidence for two psoriasis susceptibility loci (HLA and 17q) and two novel candidate regions (16q and 20p) by genome-wide scan. Human Molecular Genetics 1997;6(8):134956. NHSCRD 2001 NHS Centre for Reviews & Dissemination. Undertaking Systematic Reviews of Research on Effectiveness: CRD guidelines for those Carrying Out or Commissioning Reviews. CRD Report Number 4 (2nd edition). 2nd. York: CRD, 2001. Oh 1997 Oh PI, Gupta AK, Einarson TR, Maerov P, Shear NH. Calcipotriol in the Treatment of Psoriasis of Limited Severity: Pharmacoeconomic Evaluation. Journal of Cutaneous Medicine & Surgery 1997;2(1):715. Ortonne 2000 Ortonne JP. Psoriasis: evaluation of quality of life. Annales de Dermatologie et de Venereologie 2000;127(Suppl. 2): 2s192s22. Osborne 2002 Osborne JE, Hutchinson PE. The importance of accurate dosage of topical agents: a method of estimating involved area and application to calcipotriol treatment failures. Journal of the European Academy of Dermatology & Venereology 2002;16(4):36773. Owen 1993 Owen OG. Healthy returns come from costly drug prescribing an expensive drug may be the most costeffective way to treat patients. Healthcare Management 1993;January:523. Owen 2000 Owen CM, Chalmers RJ, OSullivan T, Grifths CE. Antistreptococcal interventions for guttate and chronic plaque psoriasis. Cochrane Database of Systematic Reviews 2000, issue 2:CD001976. Park 2002 Park YK, Lee JH, Chung WG. Allergic contact dermatitis from calcipotriol. Acta Dermato-Venereologica 2002;82(1): 712. Parodi 1991 Parodi A, Guarrera M, Volonte MV. Medicated Tape Versus Cream Formulation - a Major Saving of Fluocinolone Acetonide. Journal Of Dermatological Treatment 1991;1(6): 3056.
66
Poyner 1993 Poyner T, Hughes IW, Dass BK, Adnitt PI. Long-Term Treatment of Chronic Plaque Psoriasis with Calcipotriol. Journal Of Dermatological Treatment 1993;4(4):1737. Poyner 1999 Poyner TF, Wall ARJ, Adnitt PI, Menday AP. Economic Impact of Psoriasis Treatment on the Patient and on the National Health Service. Journal Of Dermatological Treatment 1999;10(1):259. Poyner 2000 Poyner TF, Menday AP, Williams ZV. Patient attitudes to topical antipsoriatic treatment with calcipotriol and dithranol. Journal of the European Academy of Dermatology & Venereology 2000;14(3):1538. Ramsay 1994 Ramsay CA, Berth-Jones J, Brundin G, Cunliffe WJ, Dubertret L, van de Kerkhof PC, et al.Long-Term Use of Topical Calcipotriol in Chronic Plaque Psoriasis. Dermatology 1994;189(3):2604. [PUBMED: 7949479] Richards 1999 Richards HL, Fortune DG, OSullivan TM, Main CJ, Grifths CE. Patients with psoriasis and their compliance with medication. Journal of the American Academy of Dermatology 1999;41(4):5813. Richards 2003 Richards HL, Fortune DG, Main CJ, Grifths CE. Stigmatization and psoriasis. British Journal of Dermatology 2003;149(1):20911. Richards 2006 Richards HL, Fortune DG, Grifths CE. Adherence to treatment in patients with psoriasis. Journal of the European Academy of Dermatology & Venereology 2006;20(4):3709. Russell 1972 Russell TJ, Schultes LM, Kuban DJ. Histocompatibility (HL-A) antigens associated with psoriasis. New England Journal of Medicine 1972;287(15):73840. Salvarani 1995 Salvarani C, Lo Scocco G, Macchioni P, Cremonesi T, Rossi F, Mantovani W, et al.Prevalence of psoriatic arthritis in Italian psoriatic patients. Journal of Rheumatology 1995;22 (8):1499503. Schiffner 2003 Schiffner R, Schiffner-Rohe J, Gerstenhauer M, Hofstadter F, Landthaler M, Stolz W. Willingness to pay and time trade-off: sensitive to changes of quality of life in psoriasis patients?. British Journal of Dermatology 2003;148(6): 115360. Schwicker 1992 Schwicker D, Dinkel R, Antunes HC. A Cost-Comparison Study: Ulobetasol Versus Clobetasol in Severe Localized Psoriasis. Journal Of Dermatological Treatment 1992;2(4): 12731. Senter 1983 Senter TP. Topical uocinonide and tachyphylaxis letter. Archives of Dermatology 1983;119(5):3634.
Simons 1949 Simons RD. Additional studies on psoriasis in the tropics and in the starvation camps. Journal of Investigative Dermatology 1949;12:28594. Singh 2000 Singh S, Reddy DC, Pandey SS. Topical therapy for psoriasis with the use of augmented betamethasone and calcipotriene on alternate weeks. Journal of the American Academy of Dermatology 2000;43(1 Pt 1):615. Sorensen 2002 Sorensen M, Norregaard J. Pharmacoeconomic evaluation of a new two compound ointment (Daivobet (R)) and calcipotriol (Daivonex (R)) in the treatment of psoriasis vulgaris in Sweden. Value Health 2002;5(6):5545. Staberg 1989a Staberg B, Roed-Petersen J, Menne T. Efcacy of topical treatment in psoriasis with Mc903, a new vitamin D analogue. Acta Dermato Venereologica 1989;69(2):14750. Stern 1988 Stern RS. The Benets, Costs and Risks of Topical Tar Preparations in the Treatment of Psoriasis: Considerations of Cost Effectiveness. [Review] [20 Refs]. Annals Of The Academy Of Medicine, Singapore 1988;17(4):4736. Stern 1995 Stern RS. Epidemiology of psoriasis. Dermatologic Clinics 1995;13(4):71722. Stern 1997 Stern RS. Psoriasis. Lancet 1997;350(9074):34953. Stevanovic 1977 Stevanovic DV, Wilson L, Sparkes CG. A separation of clinical from epidermal thinning effect in the topical glucocorticoid clobetasone butyrate. British Journal of Dermatology 1977;96(1):6770. Svejgaard 1974 Svejgaard A, Nielsen LS, Svejgaard E, Nielsen FK, Hjortshoj A, Zachariae H. HL-A in psoriasis vulgaris and in pustular psoriasis - population and family studies. British Journal of Dermatology 1974;91(2):14553. Szeimies 2004 Szeimies RM. Psoriasis: Patient-oriented treatment improves compliance. [German]. Haut 2004;15(5): 221223. Tagami 1997 Tagami H. Triggering factors. Clinics in Dermatology 1997; 15(5):67785. Taylor 2006 Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, et al.Classication criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis & Rheumatism 2006; Vol. 54, issue 8:266573. Tazi-Ahnini 1999a Tazi Ahnini R, Camp NJ, Cork MJ, Mee JB, Keohane SG, Duff GW, et al.Novel genetic association between
67
the corneodesmosin (MHC S) gene and susceptibility to psoriasis. Human Molecular Genetics 1999;8(6):113540. Tazi-Ahnini 1999b Tazi-Ahnini R, di Giovine FS, Cox A, Keohane SG, Cork MJ. Corneodesmosin (MHC S) gene in guttate psoriasis. Lancet 1999;354(9178):597. Tomfohrde 1994 Tomfohrde J, Silverman A, Barnes R, Fernandez-Vina MA, Young M, Lory D, et al.Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q. Science 1994;264(5162):11415. Traulsen 2003 Traulsen J, Hughes-Formella BJ. The atrophogenic potential and dermal tolerance of calcipotriol/betamethasone dipropionate ointment compared with betamethasone dipropionate ointment. Dermatology 2003;207(2):16672. Trembath 1997 Trembath RC, Clough RL, Rosbotham JL, Jones AB, Camp RD, Frodsham A, et al.Identication of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis. Human Molecular Genetics 1997;6(5): 81320. Uhoda 2003 Uhoda I, Quatresooz P, Hermanns-Le T, PierardFranchimont C, Arrese JE, Pierard GE. Histometric assessment of psoriatic plaques treated by vitamin D3 derivatives. Dermatology 2003;206(4):3669. Unna 1916 Unna PG. Cignolin als Heilmittel der Psoriasis. Dermatologische Wochenschrift 1916;62:11637. van de Kerkhof 1996c van de Kerkhof PCM, van Harten J, Verjans H. A LongTerm Assessment of the Safety and Tolerability of Calcitriol Ointment in the Treatment of Chronic Plaque Psoriasis. Journal Of Dermatological Treatment 1996;1:S11S14. van de Kerkhof 1997a van de Kerkhof PC. Combinations and comparisons. Clinics in Dermatology 1997;15(5):8314. van de Kerkhof 1997b van de Kerkhof PCM, van der Vleuten C, Gerritsen M, Glade C, Luger T, Werfel T, et al.Long-Term Efcacy and Safety of Once Daily Treatment of Chronic Plaque Psoriasis with Tacalcitol Ointment. European Journal of Dermatology 1997;7(6):4215. van de Kerkhof 1998 van de Kerkhof PCM. An update on vitamin D3 analogues in the treatment of psoriasis. Skin Pharmacology & Applied Skin Physiology 1998;11(1):210. van de Kerkhof 1998c van de Kerkhof PCM, Steegers Theunissen RP, Kuipers MV. Evaluation of topical drug treatment in psoriasis. Dermatology 1998;197(1):316.
van de Kerkhof 2000 van de Kerkhof PCM, de Hoop D, de Korte J, Cobelens SA, Kuipers MV. Patient compliance and disease management in the treatment of psoriasis in the Netherlands. Dermatology 2000;200(4):2928. van de Kerkhof 2001 van de Kerkhof PCM, Franssen M, de La Brassine M, Kuipers M. Calcipotriol cream in the morning and ointment in the evening: a novel regimen to improve compliance. J. Dermatol. Treat. 2001;12(2):759. van de Kerkhof 2002c van de Kerkhof PCM, Berth-Jones J, Grifths CE, Harrison PV, Honigsmann H, Marks R, et al.Long-term efcacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis. British Journal of Dermatology 2002;146 (3):41422. Van de Kerkhof 2008 Van de Kerkhof PCM, Barker J, Grifths CEM, Kragballe K, Mason J, Menter A, et al.Psoriasis: Consensus on topical therapies. Journal of the European Academy of Dermatology and Venereology 2008; Vol. 22, issue 7: 85970. van de Kerkhof, 2004 van de Kerkhof PC. The impact of a two-compound product containing calcipotriol and betamethasone dipropionate (Daivobet/ Dovobet) on the quality of life in patients with psoriasis vulgaris: a randomized controlled trial. British Journal of Dermatology 2004;151(3):6638. Vazquez-Lopez 2004 Vazquez-Lopez F, Marghoob AA. Dermoscopic assessment of long-term topical therapies with potent steroids in chronic psoriasis. Journal of the American Academy of Dermatology 2004;51(5):8113. Velema 2009 Velema M, Hooft L, Lebwohl M, Spuls PI. Interventions for nail psoriasis (Protocol). Cochrane Database of Systematic Reviews 2009, issue 1:Art. No.: CD007633. DOI: 10.1002/14651858.CD007633. Vissers 2004 Vissers WH, Berends M, Muys L, van Erp PE, de Jong EM, van de Kerkhof PC. The effect of the combination of calcipotriol and betamethasone dipropionate versus both monotherapies on epidermal proliferation, keratinization and T-cell subsets in chronic plaque psoriasis. Experimental Dermatology 2004;13(2):10612. Watts 1998 Watts J. Helping people to remain in control of their psoriasis. Community Nurse 1998;4(7):1921. Willan 1808 Willan R. On cutaneous diseases. London: Johnson, 1808. Wu 2005 Wu T, Jin X, Zhang M, Wei J. Traditional Chinese herbs for psoriasis (Protocol). Cochrane Database of Systematic Reviews 2005, Issue 3. Cochrane Database of Systematic
68
Reviews 2005, issue 3:Art. No.: CD005412. DOI: 10.1002/14651858.CD005412. Yui Yip 1984 Yui Yip S. The prevalence of psoriasis in the Mongoloid race. Journal of the American Academy of Dermatology 1984; 10(6):9658. Zachariae 2002 Zachariae R, Zachariae H, Blomqvist K, Davidsson S, Molin L, Mork C, et al.Quality of life in 6497 Nordic patients with psoriasis. British Journal of Dermatology 2002; 146(6):100616. Zaghloul 2004 Zaghloul SS, Goodeld MJ. Objective assessment of
compliance with psoriasis treatment. Archives of Dermatology 2004;140(4):40814. Zanolli 1992 Zanolli MD, Wikle JS. Joint complaints in psoriasis patients. International Journal of Dermatology 1992;31(7): 48891. Zug 1995 Zug KA, Littenberg B, Baughman RD, Kneeland T, Nease RF, Sumner W, et al.Assessing the Preferences of Patients with Psoriasis: A Quantitative, Utility Approach. Archives of Dermatology 1995;131(5):5618. Indicates the major publication for the study
69
CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]

Agrup 1981 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 11 TD: 3 wks; FU: 3 wks LF: 0 (0%) BC: Not reported Age: Not reported Gender (%M): Not reported Severity: Not reported INCLUSION CRITERIA Chronic plaque psoriasis; stable symmetrical lesions of the same morphology; adult EXCLUSION CRITERIA Pregnancy; receiving steroid preparations Budesonide ointment 0.025% BD (B) Placebo (vehicle) BD (P) Investigators preference Patients preference Sponsorship not reported
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up?
Authors judgement Unclear Yes
Description B - Unclear double-blind (patient / investigator)
No Yes
not reported 0.0%

70
Agrup 1981
(Continued)
Baseline assessments? Baseline comparability demonstrated?
Yes No
partial not reported
Austad 1998 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: Unclear BLINDING Double blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 49 TD: 6 wks; FU: 10 wks LF: 3 (6.1%) BC: Yes Age: 42.4 (13.9SD; range: 18 to 68) Gender (%M): 63% Severity: Duration: 15.6 (12.3SD; range: 1 to 57) TSS (0 to 9): 6.4 (0.5SD; range: 6.0 to 8.0) INCLUSION CRITERIA Adults; symmetrical plaque psoriasis, total severity score 6/9 EXCLUSION CRITERIA Widespread psoriasis; hypercalcaemia; liver or renal disease; risk of pregnancy; pregnancy; relevant concomitant medication or conditions; previous adverse response Clobetasol propionate ointment, 0.05% BD (2/52), followed by calcipotriol 50 mcg/g BD (4/52) (CP) Calcipotriol 50mcg/g BD (6/52) (C) Overall severity score (0 to 9) Investigator global assessment (6-pt: worsened to cleared) Treatment preferences, investigator Treatment preferences, patients Compliance Sponsored by Glaxo Wellcome Research and Development, Norway
Participants
Interventions
Outcomes
Notes Risk of bias Item
Authors judgement
Description
71
Austad 1998
(Continued)
Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Unclear Yes
B - Unclear double-blind (patient / investigator)
No Yes Yes Yes
not reported 6.1%
Baiocchi 1997 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: block randomisation (four patients) Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 132 TD: 8 wks; FU: 8 wks LF: 2 (1.5%) BC: Yes Age: 46.8 (15.2SD; range 18 to 89) Gender (%M): 67.4% Severity: PASI: 4.4 (2.1SD) INCLUSION CRITERIA Adult; symmetrical mild-to-moderate chronic plaque psoriasis EXCLUSION CRITERIA Recent topical or systemic antipsoriatic therapy; rapidly worsening psoriasis; concurrent vitamin D; renal or hepatic disease; pregnancy; lactation Calcipotriol ointment, 50 mcg/g, OD (C1) Calcipotriol ointment, 50 mcg/g, BD (C2) PASI Severity: erythema, scaling, induration (0 to 4 each) Global improvement score (7 pt: 0% to 90 to 100%) Cosmetic acceptability
Participants
Interventions
Outcomes
72
Baiocchi 1997
(Continued)
Notes
Sponsorship not reported All patients had a bath with salicylic acid three to four days before starting study treatments
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear No Description B - Unclear open
Yes Yes Yes Yes
block 1.5%
Barker 1999 (H) Methods DESIGN Within patient Patient delivery Method of randomisation: unclear Concealment: unclear BLINDING Double blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 30 TD: 8 wks FU: 8 wks LF: 4 (13.3%) Demographics similar; clinical characteristics not reported Age: 47.2 (14.5SD, N = 144)(range: 20 to 75) Gender (%M): 59.7% (86/144) Severity: Not reported INCLUSION CRITERIA Chronic plaque psoriasis; stable bilateral lesions affecting < 20% total body surface area; adult (18 to 85) EXCLUSION CRITERIA Pregnancy; concomitant disease; known hypersensitivity to vitamin D derivatives; systemic treatments within previous 1 mth; systemic retinoids within previous 2 mths; plaques < 10 cm2 or > 150 cm2
Participants
73
Barker 1999 (H)
(Continued)
Interventions
Dose ranging study including placebo, calcipotriol 50 mcg/g, Maxacalcitol, 6, 12.5, 25, 50 mcg/g OD Contrast included: Maxacalcitol, 25 mcg/g OD Calcipotriol, 50 mcg/g OD Psoriasis Severity Index (PSI): sum scores for erythema, induration and scaling (0 to 24) IAGI (6-pt: worse to cleared) PAGI (6-pt: worse to cleared) Investigator side preference Patient side preference Non-target plaques received emollient or coal tar throughout Sponsored by Chugai Pharma Europe
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / assessor)
Unclear Yes Yes Yes
not reported 13.3% partial partial
Barker 1999 (P) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double blind (unclear) WITHDRAWAL / DROPOUT Described
74
Barker 1999 (P)
(Continued)
Participants
N: 60 TD: 8 wks FU: 8 wks LF: 6 (10.0%) BC: Demographics similar; clinical characteristics not reported Age: 47.2 (14.5SD, N = 144)(range: 20 to 75) Gender (%M): 59.7% (86/144) Severity: Not reported INCLUSION CRITERIA Chronic plaque psoriasis; stable bilateral lesions affecting < 20% total body surface area; adult (18 to 85) EXCLUSION CRITERIA Pregnancy; concomitant disease; known hypersensitivity to vitamin D derivatives; systemic treatments within previous 1 mth; systemic retinoids within previous 2 mths; plaques < 10 cm2 or > 150 cm2 Dose ranging study including placebo, calcipotriol 50 mcg/g, Maxacalcitol ointment, 6, 12.5, 25, 50 mcg/g OD Contrast included: Calcipotriol ointment, 50 mcg/g OD (C) Placebo ointment (vehicle) (P) Psoriasis Severity Index (PSI): sum scores for erythema, induration and scaling (0 to 24) IAGI (6-pt: worse to cleared) PAGI (6-pt: worse to cleared) Investigator side preference Patient side preference Non-target plaques received emollient or coal tar throughout Sponsored by Chugai Pharma Europe
Interventions
Outcomes
Notes
Unclear Yes Yes Yes
75
Bernhard 1991 (1) Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 100 TD: 2 wks; FU: 2 wks LF: 4 (4%) BC: Yes Age: 49 (range: 20 to 77) Gender (%M): 61.5% Severity: at least 2 signs or symptoms 2 on a 4-pt scale Duration (yrs): 18.2 (range: 1 to 53) INCLUSION CRITERIA Bilateral, comparable psoriasis of at least moderate severity; adult; at least 2 signs or symptoms 2 on a 4-pt scale. EXCLUSION CRITERIA Not reported Halobetasol 0.05% ointment, BD (H) Placebo (Vehicle) (P) Signs: [erythema; plaque elevation; scaling; overall lesion severity) Patient global assessment (5 pt: poor to excellent) Skin atrophy Sponsored by an educational grant from Westwood-Squibb Pharmaceuticals (BMS)
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments?
Authors judgement Unclear Unclear
Unclear Yes Yes
not reported 4.0%
76
Bernhard 1991 (1)
(Continued)
Baseline comparability demonstrated?
Yes
Bernhard 1991(2) Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 72 TD: 2 wks; FU: 2 wks LF: 0 (0%) BC: Yes (demographics); clinical comparability unclear Age: 53 (range: 23 to 86) Gender (%M): 52.8% Severity: signs > = 4 on a 7-pt scale. BSA 1 to 20% Duration: 22.7 (range: 1 to 62) INCLUSION CRITERIA Plaque psoriasis of at least moderate severity; adult; signs 4 on a 7-pt scale. BSA 1 to 20% EXCLUSION CRITERIA Not reported Halobetasol 0.05% ointment, BD (H) Placebo (Vehicle) (P) Signs: [erythema; induration; scaling) Investigator global assessment (5-pt: worse to clear) Sponsored by an educational grant from Westwood-Squibb Pharmaceuticals (BMS)
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported?
Description B - Unclear Double-blind (patient / investigator)
Unclear
Not reported
77
Bernhard 1991(2)
(Continued)
Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Yes Yes Yes
0.0%
partial
Berth Jones 1992b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: balanced blocks of four using computer generated random numbers Concealment: Unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 478 TD: 8 wks; FU: 8 wks LF: for PASI: 56 (11.7%); for Response: 20 (4.2%) BC: Yes Age: 44 (range: 18 to 85) Gender (%M): 55% Severity: PASI: 9.3 Duration (yrs): 18 (12SD) INCLUSION CRITERIA Outpatients; adults; chronic stable plaque psoriasis EXCLUSION CRITERIA Previous non-response to study medications; recent systemic treatment; hypercalcaemia; abnormal renal/hepatic function; calcium or vitamin D intake; relevant concomitant medication; pregnancy; risk of pregnancy Calcipotriol ointment, 50 mcg/g BD (C) Dithranol cream (dose titration 0.1 to 2%) OD (D) PASI Investigator global assessment (5 pt: worse to cleared) Patient global assessment (5 pt: worse to cleared) Cosmetic acceptability Compliance Sponsored by Leo Pharmaceutical Products, Denmark
Participants
Interventions
Outcomes
Notes Risk of bias
78
Berth Jones 1992b
(Continued)
Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Authors judgement Unclear No
Description B - Unclear Open
Yes Yes Yes Yes
computer-generated block randomisation 11.7%
Bourke 1993b Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: patients randomised into groups A and B, then randomised to left/right application with sealed envelopes Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 19 (evaluable) TD: 8 wks; FU: 8 wks LF: NR BC: Yes (clinical only) Age: not reported Gender (%M): not reported Severity: TSS: 7.9 INCLUSION CRITERIA Adult; symmetrical chronic plaque psoriasis; outpatients EXCLUSION CRITERIA UV or systemic antipsoriatic therapy. Calcipotriol, BD (C)Calcipotriol, BD plus polythene lm at night (O) Signs: [erythema; induration; scale] Total sign score (0 to 12)
Participants
Interventions Outcomes
79
Bourke 1993b
(Continued)
Notes
Patients randomised into groups A (calcipotriol BD) and B (occlusion ON), then each patient randomised to left/right application: group A (occlusion ON / no occlusion); group B (calcipotriol BD or placebo BD) Findings reported for group A Sponsorship not reported
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear single (investigator)
Yes Unclear Yes Yes
envelope not reported partial partial
Bourke 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: Unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 24 TD: 8 wks LF: 4 (16.7%) BC: Yes (clinical only reported) Age: not reported Gender (%M): 41.7% Severity: PASI mean: 14.0 INCLUSION CRITERIA Adults; symmetrical chronic moderate chronic plaque psoriasis EXCLUSION CRITERIA Pregnancy; lactation; drugs affecting systemic calcium homeostasis; recent systemic antipsoriatic or UVB therapy
80
Participants
Bourke 1997
(Continued)
Interventions
Calcitriol, 3 mcg/g, BD (CL) Calcipotriol 50 mcg/g, BD (C) PASI Sponsored by Solvay-Duphar Ltd
Outcomes Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Description B - Unclear double-blind (patient / assessor)
Unclear Yes Yes Yes
Bruce 1994 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: Unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 114 TD: 6 wks; FU: 6 wks LF: 15 (13.2%) BC: Yes Age: 44.1 (14.6SD; range: 20 to 77) Gender (%M): 60.2% Severity: Mean duration of current episode (days): 142 (range: 0 to 601) Overall severity score, mean: 4.5 INCLUSION CRITERIA Stable plaque psoriasis; adults; at least mild overall severity; at least moderately severe plaque
81
Participants
Bruce 1994
(Continued)
elevation EXCLUSION CRITERIA Pregnancy; lactation; inadequate contraception; sensitivity to test medications; recent topical, UV or systemic treatment; recent involvement in other trials; planned sun exposure Interventions Calcipotriol ointment 0.005%, BD (C) Fluocinonide ointment 0.05%, BD (F) Signs [scaling; erythema; plaque elevation] Overall severity (total sign score and % involvement) Investigator global assessment Sponsored by Westwood Squibb Pharmaceuticals Inc. SD imputation (TSS)
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
Unclear Yes Yes Yes
not reported 13.2%
Buckley 1978 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 10 TD: 3 wks; FU: 3 wks
82
Participants
Buckley 1978
(Continued)
LF: 2 (20%) BC: Not reported Age: 21.4 (range: 9 to 41) Gender (%M): 50% Severity: not reported INCLUSION CRITERIA Active chronic psoriasis; lesions approximately symmetrically distributed. EXCLUSION CRITERIA Not reported Interventions Dead Sea salts emollient lotion, 30% (frequency of application not reported) (D) Base emollient lotion (placebo) (P) Jacoby assessment score (0 to 7 score transformed to % clinical improvement) Photographic evaluation Overall patient assessment (relative efcacy, speed of response, irritation, staining, ease of application) Sponsorship not reported
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Description B - Unclear double-blind (patient/ investigator)
Unclear Yes Yes Unclear
not reported 20.0% partial not reported
83
Camarasa 2003 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Conducted in 20 centres; stratication not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 258 TD: 6 wks; FU: 14 wks LF: 15 (5.8%) BC: Yes Age: 43.5 (14.3SD: range: 15 to 83) Gender (%M): 64.3% Severity: Duration of psoriasis (mths): mean: 199.2 (157.5SD: range: 1 to 745) %BSA: 25.5 (22.9SD: range: 1 to 95) PASI: 15.4 (10.6SD) INCLUSION CRITERIA Adults, moderate to severe chronic plaque psoriasis ( 2 on global severity score) EXCLUSION CRITERIA Systemic or intralesional therapy or photo(chemo)therapy in previous two mths; medications or conditions that might interfere with the assessment of study drugs; concomitant bacterial, fungal or viral skin conditions; clinically relevant abnormalities in laboratory parameters (calcium homeostasis and renal function); pregnancy or lactation; absence of adequate contraception, where appropriate Calcitriol 3 mcg/g ointment BD (C) Betamethasone dipropionate 0.05% ointment BD (B) IAGI (6 pt: worsening to clearance) PASI Overall global severity of lesions (5pt: 0, none to 4, very severe) Relapse rate Proportion remaining in remission (non-randomised sub-group analysis) 1 wk run-in period without treatment except tar shampoo and emollients Follow up for responders only, dened as achieving clearance or considerable improvement) Scalp excluded Sponsored by Galderma Laboratories SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias
84
Camarasa 2003
(Continued)
Unclear Yes Yes Yes
not reported 5.8%
Cannavo 2003 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: block randomisation Concealment: unclear BLINDING Blinding not reported WITHDRAWAL / DROPOUT Described N: 16 TD: 12 wks; FU: 20 wks LF: 0 (0%) BC: Yes (reported - see notes) Age: 61.1(10.1SD; range: 46 to 80) Gender (%M): 100% Severity: PASI: 10.9 (5.2SD; range: 4 to 20)) TSS (0 to 15): 7.13 (2.85SD, N = 16) INCLUSION CRITERIA Moderate chronic plaque psoriasis with at least four ngernails involved EXCLUSION CRITERIA Systemic therapy during previous 12 weeks; arthropathic psoriasis Topical oil-dissolved 70% oral cyclosporine solution (70 mg/100 ml), BD (C)Placebo (maize oil) BD (P)
Participants
Interventions
85
Cannavo 2003
(Continued)
Outcomes
TSS (Overall severity score) (0 to 15): onycholysis, hyperkeratosis, pitting, crumbling, oil drop, each scored on 4 pt scale: 0: absent to 3: severe Patient overall severity score (4 pt): minimal to very severe (baseline only) Sponsorship not reported TSS at baseline signicantly different Nail trial
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Unclear Description B - Unclear not reported
Yes Yes Yes Yes
block 0.0%
Cheesbrough 1992 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 24 TD: 12 wks; FU: 12 wks LF: 5 (20.8 %) BC: Yes Age (mean): 47 Gender (%M): 54.2% Severity: PASI mean: 26 INCLUSION CRITERIA Chronic stable plaque psoriasis
86
Participants
Cheesbrough 1992
(Continued)
EXCLUSION CRITERIA Not reported Interventions Dead sea salts emollient lotion, 30% (frequency of application not reported) (D) Base emollient lotion (placebo) (P) PASI Erythema, scaling, thickening, pruritus Adverse events Finders Dead Sea Salt Co and Dead Sea Salt works supplied the study treatments
Outcomes
Unclear Yes Yes Yes
not reported 20.8%
Christensen 1999 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Single-blind at inclusion only (investigator) WITHDRAWAL / DROPOUT Described N: 171 TD: 8 wks; FU: 16 wks (N = 95) LF: 5 (2.9%) BC: Yes Age: 47.4 (range: 17 to 88) Gender (%M): 62.6%
87
Participants
Christensen 1999
(Continued)
Severity: Mean TSS (0 to 9): 6.24 Mean duration of psoriasis: 18.5 (range: 1 to 58) INCLUSION CRITERIA Outpatients with mild to severe chronic stable chronic plaque psoriasis, not more than 10% BSA, total severity score (0 to 9) 4, involving all three signs (erythema, scaling, inltration) EXCLUSION CRITERIA Systemic treatment within previous 4 wks; topical treatment within previous 2 wks; receipt of oral retinoids within previous 2 mths Interventions Short contact dithranol (30 min), 1% to 3%, OD (D) Calcipotriol, 50 mcg/g, BD (C) Total severity score (0 to --9) Pruritus (0 to 3) Investigators Global Assessment (7pt: worse to completely clear) Patients Global Assessment (6pt: worse to completely clear) Adverse events Sponsorship: not reported Study also included 16-week follow-up data for consenting patients who achieved at least 50% improvement from baseline (Investigator scale) SD imputation (TSS)
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear single-blind (investigator)
Unclear Yes Yes Yes
not reported 2.9%
88
Crosti 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Unclear WITHDRAWAL / DROPOUT Described N: 160 TD: 6 wks; FU: 10 wks LF: 8 (5%) BC: Yes Age: 49.9 (14.2SD) Gender (%M): 68.1% Severity: Mean PASI: 7.6 INCLUSION CRITERIA Mild, stable chronic plaque psoriasis; adult EXCLUSION CRITERIA Recent topical or systemic treatments; pregnancy; lactation; concomitant vitamin D or systemic steroids; hepatic or renal failure Calcipotriol ointment, 50mcg/g, BD (C) Betamethasone dipropionate + salicylic acid, BD (B) PASI Investigator global assessment Patient global assessment of acceptability of treatment (5 pt: nil to excellent) Sponsorship: not reported SD imputation (PASI)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Authors judgement Unclear Unclear Description B - Unclear not reported
Unclear Yes Yes
not reported 5.0%
89
Crosti 1997
(Continued)
Yes
Cunliffe 1992 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: balanced blocks of 10 according to a computer generated random numbers table Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 409 TD: 6 wks; FU: 6 wks LF: 8 (2.0%) BC: Yes Age: 44.9 (range: 17 to 83) Gender (%M): 55.7% Severity: Mean PASI: 9.0 (range: 0.6 to 41.2) Mean duration psoriasis: 16.2 (range: 0.2 to 57) INCLUSION CRITERIA Stable plaque psoriasis; adult; outpatients EXCLUSION CRITERIA Risk of pregnancy; pregnancy; lactation; recent systemic antipsoriatic treatment Calcipotriol ointment, 50mcg/g, BD (C) Betamethasone-17-valerate 1 mg/g, BD (B) PASI Patient overall assessment (5 pt: worse to clear) Sponsored by Leo Pharmaceuticals
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes
90
Cunliffe 1992
(Continued)
Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Yes Yes Yes Yes
computer-generated block 2.0%
De Simone 1993 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Blinding unclear WITHDRAWAL / DROPOUT Not described N: 30 TD: 6 wks; FU: 10 wks LF: 0 (0%) BC: Not reported Age: range: 18 to 84 Gender (%M): 70.0% Severity: PASI range: 2.7 to 24.3 INCLUSION CRITERIA Chronic plaque psoriasis EXCLUSION CRITERIA Pregnancy, lactation, hepatic or renal disease; recent systemic or topical therapy; high intake of vitamin D or calcium Calcipotriol ointment, 50mcg/g, BD (C) Coal tar 5% in Lassars paste (T) Investigator global assessment (estimated from PASI score) Sponsorship: not reported
Participants
Interventions
Outcomes Notes Risk of bias Item Allocation concealment?
Authors judgement Unclear
Description B - Unclear
91
De Simone 1993
(Continued)
Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated?
Unclear
not reported
Douglas 2002 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated randomisation schedule Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 1106 TD: 4 wks; FU: 4 wks LF: 86 (7.8%) BC: Yes Age: mean: 47.1 (range: 18 to 89) Gender (%M): 59.8% Severity: PASI: 10.7 (range: 2.1 to 39.6) Duration: mean 18.4 (range: 0 to 65) INCLUSION CRITERIA Chronic plaque psoriasis; aged at least 18 years; use of systemic antipsoriatic treatment / phototherapy in previous 6 weeks; treatment of lesions contraindicated for topical corticosteroid therapy EXCLUSION CRITERIA Pregnancy; lactation; current participation in other trial; abnormality of calcium metabolism; hypercalcaemia Calcipotriol (50 mcg/g) /betamethasone (0.5 mg/g) combination ointment (Daviobet), BD (D) Calcipotriol ointment (Daivonex), 50 mcg/g, BD (C) Betamethasone dipropionate ointment (Diprosone), 0.5 mg/g, BD (B) All groups then received four weeks of maintenance therapy with calcipotriol BD
Participants
Interventions
92
Douglas 2002
(Continued)
Outcomes
PASI (modied) (0 to 64.8) Redness, thickness, scaling (0 to 8 each) Investigator global assessment (6-pt: worse to cleared) Patients assessment of treatment response (6-pt: worse to cleared) Adverse events Sponsored by Leo Pharmaceuticals Four week follow-up study also reported (open design: all patients received calcipotriol)
Notes
Yes Yes Yes Yes
computer-generated 7.8%
Dubertret 1992 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 66 TD: 4 wks; FU: 8 wks LF: 6 (9.1%) BC: Yes Age: 43 (range: 21 to 84) Gender (%M): 69.7% Severity: duration: 13.3 (range: 0.3 to 40.0) PASI: mean: 14.15
93
Participants
Dubertret 1992
(Continued)
INCLUSION CRITERIA Bilateral stable symmetric chronic plaque psoriasis of the arms, limbs or trunk; adult EXCLUSION CRITERIA Guttate or pustular psoriasis; psoriasis restricted to the scalp, face, elbows or knees; recent systemic or UV therapy in the previous; calcium, vitamin D daily or other medications; hepatic or renal impairment; planned exposure to sun Interventions Calcipotriol ointment 50 mcg/gm BD (C) Placebo (vehicle) (P) Severity [erythema, inltration, desquamation] Modied PASI Preferred treatment Investigator global assessment (5pt: cleared to worse) Patient global assessment (5pt: cleared to worse) Sponsored by Leo Pharmaceuticals Contact Leo for patient outcome data SD imputation (TSS)
Outcomes
Notes
Unclear Yes Yes Yes
not reported 9.1%
94
Durakovic 2001 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: Not stated Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 15 TD: 12 wks; FU: 20 wks LF: 0 (0%) BC: Yes Age: 49 (range: 27 to 76) Gender (%M): 80% Severity: TSS (0 to 24): 13.7 (14.7SD) INCLUSION CRITERIA Chronic plaque psoriasis involving at least 5% BSA; bilateral lesions of approximately 25 cm EXCLUSION CRITERIA Systemic treatment within previous 30 days; topical treatment within previous 1 day; history of hepatic or renal failure; nephrolithiasis; hypercalcaemia; hypercalciuria; pregnancy; lactation; unwillingness in females to use effective contraception Hexauoro-1,25-dihydroxyvitamin D3 , 5 mcg/g in 0.1g of ointment, BD (F6) Placebo ointment, BD (P) Total severity score (0 to 24) PASI (0 to 72) Investigators assessment of global improvement (5 pt: worsening to excellent improvement) Sponsored by the National Institutes of Health and by Penederm Inc. Eight week follow up (open design: all patients received study drug) study also reported
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
Unclear Yes
not reported 0.0%

95
Durakovic 2001
(Continued)
Yes Yes
Durakovic 2004 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 11 TD: 12 wks; FU: 12 wks LF: 0 (0%) BC: yes Age: 46 (range: 29 to 65) Gender (%M): 72.7% Severity: TSS (0 to 12): 9.30 INCLUSION CRITERIAModerate plaque psoriasis; BSA 5%; 2 target lesions with diameter 5cm; severity score (0 to 4) 2 for each of plaque elevation, scaling and erythema EXCLUSION CRITERIA Previous topical therapy within previous two wks; systemic therapy within previous four wks; pregnancy or risk thereof; lactation; hepatic failure; renal failure; hypercalcaemia; hypercalciuria; hyperphosphataemia; concurrent calcium supplements or drugs inuencing calcium metabolism Paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D2 ) ointment, 15 mcg/g, OD (PC) Placebo ointment, OD (P) Global severity score (0 to 12) (erythema, plaque elevation, scaling) Global treatment success rates (IAGI) (4 pt: excellent, moderate, mild or no improvement) Sponsored in part by grant from the National Institutes for Health, USAbbott Laboratories supplied the study drug
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Authors judgement Unclear Description B - Unclear
96
Durakovic 2004
(Continued)
Yes
double-blind (patient / investigator)
Unclear Yes Yes Yes
not reported 0.0%
Duweb 2000 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING unclear WITHDRAWAL / DROPOUT Described N: 42 TD: 6 wks; FU: unclear LF: 0 (0%) BC: Clinical only Age: 33.5 (range: 6 to 61) Gender (%M): 69% Severity: TSS (0 to 12): 5.2 INCLUSION CRITERIA Psoriasis of the scalp EXCLUSION CRITERIA Not reported Calcipotriol 50 mcg/g/ml solution, BD (C) Betamethasone valerate 1% lotion, BD (B) Redness, thickness, scaliness (0 to 4) Total Severity Score (0 to 12) Adverse events Sponsored by Leo Pharmaceuticals SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias
Topical treatments for chronic plaque psoriasis (Review) Copyright 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. 97
Duweb 2000
(Continued)
Description B - Unclear not reported
Unclear Yes Yes Yes
not reported 0.0%
partial
Elie 1983 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 40 (55% psoriasis) TD: 3 wks; FU: 3 wks LF: Not reported BC: Yes Age: 36.5 (range: 20 to 63) Gender (%M): 40% Severity: not reported INCLUSION CRITERIA Moderate to severe psoriasis, seborrhoeic dermatitis or neurodermatitis of the scalp; adult. EXCLUSION CRITERIA None reported Betamethasone-17,21-dipropionate, 0.05% BD (B) Salicylic acid 2% BD (S) Betamethasone-17,21-dipropionate, 0.05% + Salicylic acid 2% BD (BS) Placebo (vehicle) (P)
Participants
Interventions
98
Elie 1983
(Continued)
Outcomes
Investigator global assessment (5-pt: very severe to clear) Severity [redness; scaling; pruritis] Area of lesion (cm) Sponsorship: sponsored by Schering Canada Inc. Scalp trial SD imputation (TSS/IAGI)
Notes
Unclear Unclear Yes Yes
not reported not reported partial
Ellis 1988 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated randomisation list (1:1) Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 165 TD: 3 wks; FU: 3 wks LF: 33 (20%) BC: Yes Age: 49.1 (range: 19 to 82) Gender (%M): 51.6% Severity: not reported INCLUSION CRITERIA
99
Participants
Ellis 1988
(Continued)
Psoriasis of the scalp; adult; TSS (0 to 12) 6; patients required to have psoriatic lesions elsewhere. EXCLUSION CRITERIA Acute systemic illness; active skin infection; concomitant antihistamine, topical or systemic corticosteroid, antimetabolites, PUVA, or other dermatological treatment; recalcitrant psoriasis; intolerance or hypersensitivity to topical corticosteroids; pregnant or lactating Interventions Amcinonide lotion 0.1% OD (A) Placebo (vehicle) (P) Severity: [erythema; excoriation; scaling; induration, pruritis] Total sign score [erythema; scaling; induration, pruritis] Investigators Overall Evaluation (7 pt: cleared to exacerbation) Patients Overall Evaluation (4 pt: poor to excellent) Patient Acceptability Evaluation. Sponsorship: not reported Compliance checked by counting returned bottles Scalp trial SD imputation (TSS)
Outcomes
Notes
Yes Yes Yes Yes
100
Escobar 1992 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: randomised code Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 25 TD: 4 wks; FU: 8 wks LF: 0 (0%) BC: Yes Age: 40.3 (14.1SD), range: 18 to 66 Gender (%M): 56.0% Severity: mean TSS (0 to 12): 7.83 INCLUSION CRITERIA Clinical and histopathological diagnosis of psoriasis EXCLUSION CRITERIA Systemic cytostatic / corticosteroid therapy within previous year; renal, hepatic, haematological disease; NSAIDs, beta adrenergic receptor blockers, antimalarial drugs Fish oil plus 6-hour occlusion, OD (FO) Liquid parafn plus 6-hour occlusion, OD (LP) Erythema, scaling, thickening (0 to 4) Pruritis (VAS) Patient acceptability Sponsorship: not reported SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Authors judgement Unclear Yes Description B - Unclear single (investigator)
Unclear Yes Yes
not reported 0.0%
101
Escobar 1992
(Continued)
Yes
Farkas 1999 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: computer programme randomised patients in blocks of 10 Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 84 TD: 8 wks; FU: 12 wks LF: 0 (0%) BC: Yes Age: 45.1 (range: 18 to 69) Gender (%M): 60.7% Severity: mean PASI: 13.2% BSA (mean): 16.5% INCLUSION CRITERIA Chronic stable plaque psoriasis; adults; Caucasian patients = 30% BSA; mPASI > 10; inand outpatients EXCLUSION CRITERIA Recent topical, systemic or UV therapies; sensitivity to study medications; concurrent medication; abnormal hepatic or renal function; risk of pregnancy; pregnancy; lactation; serious co-morbidity Tacalcitol ointment, 4 mcg/g, OD (T) Dithranol stick, 1.5% or 3%, OD (D) PASI (modied to exclude head) Total sign score: [erythema, inltration and desquamation] Investigator global assessment Patients evaluation of benet (10 pt) Investigator evaluation of efcacy and tolerability (1, very good to 4, very bad) Patient evaluation of efcacy and tolerability (1, very good to 4, very bad) Sponsored by Hermal
Participants
Interventions
Outcomes
Authors judgement
Description
102
Farkas 1999
(Continued)
Unclear No
B - Unclear open
Yes Yes Yes Yes
computer-generated block 0.0%
Franz 1999 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 190 TD: 2 wks; FU: 4 wks LF: 18 (9.5%) BC: Yes Age: 49.6 Gender (%M): 49.3% Severity: mean TSS (0 to 12): 7.92 INCLUSION CRITERIA Moderate to severe scalp psoriasis (each of 3 primary signs 2); scalp involvement 10%; adults EXCLUSION CRITERIA Systemic psoriatic therapy within previous four wks; topical scalp preparations within previous two wks Betamethasone valerate foam, 0.1%, BD Placebo foam, BD Betamethasone valerate lotion, 0.1%, BD Placebo lotion, BD Findings reported for foam and lotion combined: Betamethasone (B) Placebo (P)
103
Participants
Interventions
Franz 1999
(Continued)
Outcomes
Erythema, scaling, thickness, pruritis IAGI (7 pt: worse to completely clear) PAGI (7 pt: worse to completely clear) Sponsorship: sponsored by Connectics Corporation Scalp trial SD imputation (TSS)
Notes
Unclear Yes Yes Yes
not reported 9.5%
Franz 2000 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 188 TD: 2 wks; FU: 4 wks LF: 0(0%) BC: unclear Age: not reported Gender (%M): 49.5% Severity: Mean TSS (0 to 12): 7.25 INCLUSION CRITERIA Moderate to severe scalp psoriasis (each of 3 primary signs 2); scalp involvement 10%;
104
Participants
Franz 2000
(Continued)
adults EXCLUSION CRITERIA Not reported Interventions Clobetasol propionate foam, 0.05%, BD Placebo foam, BD Clobetasol propionate lotion, 0.05%, BD Placebo lotion, BD Findings reported for foam and lotion combined: Clobetasol (C) Placebo (P) Signs: erythema, scaling, thickness, pruritis TSS (0 to 12) IAGI (7 pt: worse to completely clear) PAGI (7 pt: worse to completely clear) Sponsorship: sponsored by Connectics Corporation Scalp trial SD imputation (TSS)
Outcomes
Notes
105
Geilen 2000 Methods DESIGN Within patient Nurse delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 7 TD: 3 wks; FU: 3 wks LF: 0 (0%) BC: Yes Age: 36 to 67 Gender (%M): 100% Severity: TSS (0 to 8): 6.72 (0.76SD) INCLUSION CRITERIA Chronic plaque psoriasis EXCLUSION CRITERIA Not reported Mycophenolic acid ointment, 1% plus occlusion, OD (M) Placebo ointment, plus occlusion, OD (P) TSS (erythema induration) (0 to 8) Sponsorship not reported
Participants
Interventions
Unclear Yes Yes Yes
not reported 0.0% partial
106
Gottlieb 2003 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Conducted in 17 centres; stratication not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 279 TD: 2 wks; FU: 4 wks LF: 8 (2.9%) BC: Yes (clinical only) Age: 47 (range: 19 to 82) Gender (%M): 57% Severity: BSA: 6.7% INCLUSION CRITERIA Aged 18 to over; mild to moderate chronic plaque psoriasis of nonscalp regions; 2 > PSGA > 3; BSA < = 20%; target lesion > 2cm2 on trunk or extremities with PGSA between 2 and 3 for each of erythema, scaling and plaque thickness EXCLUSION CRITERIA Known allergy to study medications or other topical corticosteroids; systemic therapy within previous eight wks; topical corticosteroid therapy or retinoids within previous four wks; other topical therapy within previous two wks; expected exposure to strong sunlight / UVB therapy during study period; pregnancy, or risk thereof; lactation Clobetasol foam (OLUX) 0.05%, BD (C) Placebo foam, BD (P) Limit of 50g of medication/wk to nonscalp sites only Signs and symptoms of psoriasis: (6 pt scale for each: induration, erythema, scaling, pruritis) Physicians Static Global Assessment (PGSA) (6 pt: 0 = clear to 5 = majority of lesions have individual scores that average 5 on a 6 pt scale) Proportion of patients with PSGA score < = 1 at 2 wks Mean change in total sign scores (0 to 15) Patient Global Assessment (PGA) (6 pt: 0 = no psoriasis; 5 worst during current exacerbation) Patient assessment of likely compliance Patient assessment of cosmetic acceptability Sponsored by the Connetics Corporation SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Authors judgement Description

107
Gottlieb 2003
(Continued)
Unclear Yes
Unclear Yes Yes Yes
not reported 2.9%
partial
Grattan 1997 (H) Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: pre-determined randomisation schedule Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 25 TD: 4 wks; FU: 16 weeks LF: not reported BC: Yes Age: 44.0 (range: 20 to 72) Gender (%M): 52.0%) Severity: BSA: 16.1% (range 4.1% to 47.8%) TSS (target sites): 6.3 (range NR) INCLUSION CRITERIA Bilateral stable chronic plaque psoriasis; adult; hospitalised for routine dithranol treatment. EXCLUSION CRITERIA Intolerance of dithranol; unstable or pustular psoriasis; calcium metabolism disorders; systemic psoriasis treatment; recent UVB or PUVA therapy; pregnancy or lactation Calcipotriol ointment, 0.005% BD (C) Dithranol in aqueous gel, (dose titration 0.1 to 2.0%), BD (D) Severity: [erythema; scaling; palpability] Total severity score Patient assessment of irritation (VAS) Investigator assessment of skin staining (none, mild, moderate or severe)
108
Participants
Interventions
Outcomes
Grattan 1997 (H)
(Continued)
Notes
Inpatient treatment to ensure high level of compliance Sponsored by Dermal Laboratories
not reported not reported
Grattan 1997 (P) Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: pre-determined randomisation schedule Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 12 TD: 4 wks: FU: 16 wks LF: 0 (0%) BC: Yes Age: 50.3 (range:33 to 75) Gender (%M): 33% (4/12) Severity: BSA: 17.1% (range 4.7% to 45.7%) TSS: 6.3 (range: 5 to 7) INCLUSION CRITERIA Bilateral stable chronic plaque psoriasis; adult; hospitalised for routine dithranol treatment EXCLUSION CRITERIA Intolerance of dithranol; unstable or pustular psoriasis; calcium metabolism disorders; systemic psoriasis treatment; recent UVB or PUVA therapy; pregnancy or lactation
Participants
109
Grattan 1997 (P)
(Continued)
Interventions
Dithranol in aqueous gel, (dose titration 0.1 to 2.0%), BD (D) Placebo (vehicle) (P) Severity: [erythema; scaling; palpability] Total severity scorePatient assessment of irritation (VAS) Investigator assessment of skin staining (none, mild, moderate or severe) Inpatient treatment to ensure high level of compliance Sponsored by Dermal Laboratories
Outcomes
Notes
Unclear Yes Yes Yes
not reported 0.0%
Green 1994 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 49 TD: 4 wks; FU: 4 wks LF: 3 (6.1%) BC: unclear Age: not reported Gender (%M): not reported Severity: mean TSS (0 to 12): 6.7
110
Participants
Green 1994
(Continued)
INCLUSION CRITERIA Mild to moderate scalp psoriasis and a history of psoriasis elsewhere on the body; adult. EXCLUSION CRITERIA Excessively thick scalp psoriasis. Other scalp disease; marked deterioration of scalp psoriasis at entry; recent systemic or UV therapy; concurrent topical corticosteroid use; vitamin D or calcium supplement; medications which could affect the course of the disease; hypercalcaemia; hepatic or renal disease; at risk of pregnancy Interventions Calcipotriol solution, 50mcg/ml, BD (C) Placebo (vehicle) (P) Signs [erythema; thickness; scaliness; aking; itching] Total Sign Score [redness, thickness, scaliness] Investigator global assessment Patient global assessment Sponsored by Leo Pharmaceutical Products Compliance assessed by unused medication returned at each visit. Compliance rate for patients in each group > 90%. Scalp trial
Outcomes
Notes
111
Greenspan 1993 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 80 TD: 3 wks; FU: 3 wks LF: 9 (11.3%) BC: unclear Age: 51.5 (range: 20 to 77) Gender (%M): 43.8% Severity: not reported INCLUSION CRITERIA Mild to moderate psoriasis EXCLUSION CRITERIA Recent systemic or topical treatment for psoriasis; contraindication to low-potency corticosteroids; pregnant, nursing or planning pregnancy Desonide lotion, 0.05% TDS (DL) Desonide cream, 0.05% TDS (DC) Placebo (vehicle lotion) (P) Severity: [erythema; scaling; induration; pruritis] Investigator global assessment Sponsorship: not stated, but three of the authors employed by Owen / Galderma laboratories SD imputation (IAGI)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
Unclear Yes Yes

112
Greenspan 1993
(Continued)
Unclear
not reported
Gribetz 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: validated system that automates the random assignment of treatment codes. Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 57 TD: 8 wks; FU: 8 wks LF: 6 (10.5%) BC: Yes Age: 47.8 (range: 21 to 88) Gender (%M): 50.9% Severity: PGA, % moderate: 72% PGA, % severe: 29.8% TSS: 5.34 (range: 3.0 to 9.0) INCLUSION CRITERIA Stable, chronic plaque psoriasis; moderate to severe inverse psoriasis affecting axillae, inguinal, inframammary or gluteal cleft regions (duration 6 mths); PGA 3; erythema 2; aged 18 EXCLUSION CRITERIA Clinically signicant laboratory abnormalities; hypersensitivity to study drug or vehicle; systemic, phototherapy or immuno-modifying agents within previous 30 dys; topical therapies within previous 14 dys; unstable plaque psoriasis, pustular, drug associated or erythrodermic psoriasis Pimecrolimus cream (Elidel), 1% BD (PM) Placebo cream, BD (P) Investigators Global Assessment of overall severity (PGA) (5 pt: clear to severe disease) Target Area Score (TSS) (erythema, induration, scaling) (0 to 9) Patient Self-Assessment (control of psoriasis over previous 1wk) (4 pt: 0 = complete control; 3 =u ncontrolled) Sponsored by Novartis Pharmaceuticals Group No instances of skin atrophy reported inverse psoriasis
113
Participants
Interventions
Outcomes
Notes
Gribetz 2004
(Continued)
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Yes Yes Description A - Adequate double-blind (patient / investigator)
Unclear Yes Yes Yes
not reported 10.5%
Guenther 2000 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 120 TD: 8 wks; FU: 20 wks LF: 14 (11.7%) BC: Yes Age: 48.5 Gender (%M): 60.8% Severity: not reported INCLUSION CRITERIA Stable chronic plaque psoriasis; BSA involvement between 5% and 20%; adult EXCLUSION CRITERIA Pregnancy; lactation; unreliable contraception; unstable plaque psoriasis; other types of psoriasis or other concomitant dermatological disorder; hypercalaemia; uncontrolled systemic disease; likelihood of prolonged UV exposure; concomitant systemic or topical therapies that might affect psoriasis; adherence to washout requirements
Participants
114
Guenther 2000
(Continued)
Interventions
Tazarotene gel, 0.1%, ON, plus mometasone furoate cream, 0.1%, OM (TM) Calcipotriol ointment, 0.005%, BD (C) 12 weeks maintenance for both groups with emollient only. IAGI (0 to 6; exacerbation to complete clearance) Erythema, scaling, thickness (0 to 4 for each) BSA involvement Patient assessments (efcacy, comfort of skin; outlook for long-term control; overall impression of treatment) Adverse events Sponsored by Allergan Inc.
Outcomes
Description B - Unclear single (investigator)
Unclear Yes Yes Yes
not reported 11.7%
Guenther 2002 (H) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Computer-generated random numbers table Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 828 TD: 4 wks; FU: 4 wks LF: 10 (1.2%) BC: Yes
115
Participants
Guenther 2002 (H)
(Continued)
Age: 48.5 (14.3SD) Gender (%M): 64.0% Severity: Mean PASI: 10.5 Mean duration psoriasis: 18.3 yrs INCLUSION CRITERIA Aged 18 to 86; chronic plaque psoriasis; BSA involvement 10% EXCLUSION CRITERIA Systemic therapy within previous six wks; topical antipsoriatic therapy within previous two wks; concurrent use of type III / IV topical corticosteroids; recent UV exposure; pregnancy; lactation; concurrent use of other medicines that could affect course of psoriasis Interventions Calcipotriol (50 mcg/g) and betamethasone dipropionate (0.5 mg/g) ointment, ON, plus placebo, OM (D1) Calcipotriol (50 mcg/g) and betamethasone dipropionate (0.5 mg/g) ointment, BD (D2) Calcipotriol, BD (C) Placebo, BD (P) PASI (head excluded) IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Percentage change in thickness score Speed of response (PASI) at one week Adverse events Quality of life: Psoriasis Disability Index EQ-5D and EQ-VAS (reported in van de Kerkhof 2004) Sponsored by Leo Pharmaceuticals 57 centres in 8 countries
Outcomes
Notes
Yes Yes Yes Yes
Computer-generated 1.2%
116
Guenther 2002 (P) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Computer-generated random numbers table Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 828 TD: 4 wks; FU: 4 wks LF: 10 (1.2%) BC: Yes Age: 48.5 (14.3SD) Gender (%M): 64.0% Severity: Mean PASI: 10.5 Mean duration psoriasis: 18.3 yrs INCLUSION CRITERIA Aged 18 to 86; chronic plaque psoriasis; BSA involvement 10% EXCLUSION CRITERIA Systemic therapy within previous six wks; topical antipsoriatic therapy within previous two wks; concurrent use of type III / IV topical corticosteroids; recent UV exposure; pregnancy; lactation; concurrent use of other medicines that could affect course of psoriasis Calcipotriol (50 mcg/g) and betamethasone diproprionate (0.5 mg/g) ointment, ON, plus placebo, OM (D1) Calcipotriol (50 mcg/g) and betamethasone diproprionate (0.5 mg/g) ointment, BD (D2) Calcipotriol, BD (C) Placebo, BD (P) PASI (head excluded) IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Percentage change in thickness score Speed of response (PASI) at one week Adverse events Quality of life: Psoriasis Disability Index EQ-5D and EQ-VAS (reported in van de Kerkhof 2004) Sponsored by Leo Pharmaceuticals 57 centres in 8 countries
Participants
Interventions
Outcomes
Notes
Risk of bias
117
Guenther 2002 (P)
(Continued)
Authors judgement Yes Yes
Description A - Adequate double-blind (patient / investigator)
Yes Yes Yes Yes
Han 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 208 TD: 12 wks; FU: 12 wks LF: 9 (4.3%) BC: Yes Age: 40.4 (8.9SD) Gender (%M): 59.8% Severity:TSS (0 to 20): 16.1 (11.0SD) Duration (yrs): 9.4 (8.9SD) INCLUSION CRITERIA Patients with chronic plaque psoriasis; aged between 18 and 65; BSA between 2% and 30% EXCLUSION CRITERIA Known allergy to study drug constituents; history of other skin diseases; pustular or erythrodermic psoriasis; topical treatments within previous two wks; PUVA within previous four wks; UVB within previous two wks; alcohol or drug abuse; renal, hepatic or immunity disorder; pregnancy or risk thereof; lactation; participation in another clinical trial within previous four wks; other morbidity likely to affect outcome or raise safety issues Tazarotene gel, 0.05%, OD (T) Calcipotriol ointment, 5 mcg/g, BD (C)
118
Participants
Interventions
Han 2001
(Continued)
Outcomes
TSS: (0 to 20?) Proportion of patients achieving effective response Curative rate Sponsorship not reported
Description B - Unclear open
Unclear Yes Yes Yes
not reported 4.3%
Harrington 1996a Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 413 TD: 8 wks; FU: 8 wks LF: 47 (11.4%) BC: Yes, except average age in placebo group higher than for A and B p = 0.02 Age: 44.6 Gender (%M): 52.8% Severity: PASI (modied): 8.3 (range: 0.6 to 59.4) Duration (yrs): 17.7 (range: 0.04 to 70) INCLUSION CRITERIA Stable chronic plaque psoriasis on trunk or limbs; adult.
119
Participants
Harrington 1996a
(Continued)
EXCLUSION CRITERIA Recent systemic medication or phototherapy for psoriasis; hepatic or renal disease; raised serum calcium; calcium supplements or vitamin D Interventions Calcipotriol cream, 50 mcg/g BD as: Cream A (dissolved) (CA) Cream B (suspended) (CB) Placebo (vehicle of A) (P) PASI (modied to exclude head) Investigator global assessment Patient global assessment Sponsored by Leo Pharmaceuticals
Outcomes
Unclear Yes Yes Yes
not reported 11.4%
partial
Henneicke-v. Z. 1993 Methods DESIGN Within patient (placebo) Between patient (active) Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
120
Henneicke-v. Z. 1993
(Continued)
Participants
N: 73 TD: 8 wks; FU: 8 wks LF: 21 (28.8%) BC: Yes Age: 40.5 (median), range: 18 to 71 (N = 52) Gender (%M): 65.8% (N = 73) Severity: TSS (0 to12): 7.4 INCLUSION CRITERIA Aged 18 to 71; moderate plaque psoriasis; 9 >TSS 4 EXCLUSION CRITERIA Systemic antipsoriatic drugs within previous four wks; UV therapy within previous one wk; drug-induced psoriasis; cancer; pregnancy; lactation; severe organ dysfunction; metabolic disorders; abuse of drugs or alcohol Omega-3-polyunsaturated fatty acids ointment, 1%, BD (O3(1)) Placebo (vehicle), 1%, BD Omega-3-polyunsaturated fatty acids ointment, 10%, BD (O3(10)) Placebo (vehicle), 10%, BD (P) Local psoriasis severity index (TSS equivalent): erythema, induration, desquamation Area of indicator lesion Pruritis Investigators subjective intra-individual comparison (left side better than right side) Patients subjective intra-individual comparison (left side better than right side) Compliance: tube weight compared with expected use Sponsorship: not reported
Interventions
Outcomes
Unclear Yes Yes Yes
not reported 28.8%
121
Highton 1995 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 277 TD: 8 wks LF: 30 (10.8%) BC: Clinical severity comparable, demographics unclear Age: not reported Gender (%M): not reported Severity: TSS (0 to 8): 3.90 BSA: 9.1% INCLUSION CRITERIA Moderately severe stable plaque psoriasis; plaque elevation score ? 4 (0 to 8); Not pregnant or nursing during the duration of the study. EXCLUSION CRITERIA Recent topical or systemic psoriasis treatment, prolonged exposure to sunlight, phototherapy; photochemotherapy; hypercalcemia; erythrodermic or pustular psoriasis. Calcium, vitamin A or D supplements Calcipotriene ointment 0.005%, BD (C) Placebo (vehicle) (P) Severity:[erythema; plaque elevation; scaling; overall disease severity] 75% improvement scores Investigator global assessment (7-pt: worse to completely clear) Sponsored by Bristol Myers Squibb SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
Unclear
not reported
122
Highton 1995
(Continued)
Yes Yes Yes
10.8% partial partial
Holick 2003 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 15 TD: 8 wks FU: 8 wks LF: 0 (0%) BC: not reported Age: 56 (range: 25 to 74) Gender (%M): 67 % Severity: not reported INCLUSION CRITERIA Chronic plaque psoriasis; two symmetrically comparable plaques, failure to respond to at least one standard treatment EXCLUSION CRITERIA Kidney disease, hypercalcaemia, hypercalciuria; systemic therapy within previous 30 days; topical therapy within previous 14 days; concomitant medications that interfere with calcium metabolism PTH (1 to 34), 20 mcg/g in Novasome A liposomal cream, BD (PTH) Novasome A liposomal cream, BD (P) Global severity score (0 to 24) PASI (for open trial phase only) Sponsored by grants from the National Institutes for Health (Department of Health and Human Services) and the Department of Defense Small Business Innovation Research (SBIR) Program Also reports uncontrolled open, large area, study for N = 10; PTH applied OD for up to 11 months PTH: parathyroid hormone
Participants
Interventions
Outcomes
Notes
123
Holick 2003
(Continued)
Hutchinson 2000 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: Unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 114 TD: 8 wks; FU: 8 wks LF: 28 (24.6%) BC: Yes Age: 42.3 Gender (%M): 74.4% Severity: Duration of psoriasis, mths, (mean): 185.1 (range: 1 to 85) PASI (mean): 11.8 INCLUSION CRITERIA Chronic plaque psoriasis of at least moderate severity, aged over 18; Caucasian or Asian origin EXCLUSION CRITERIA Systemic or intralesional therapy or photo-chemotherapy within previous two mths; topical antipsoriatics within previous wk or concomitant; other medications that could affect psoriasis; pregnancy; inadequate contraception
124
Participants
Hutchinson 2000
(Continued)
Interventions
Calcitriol ointment, 3 mcg/g BD (C) Short contact dithranol, 0.25 to 2%, OD (D) PASI IAGI (6 pt: worse to clearing) Overall global severity (5 pt: none to v. severe) Psoriasis Disability Index (quality of life) (scale NR) Cosmetic acceptability (1, good/none to 3, not acceptable): staining, irritation Adverse events Sponsorship not reported
Outcomes
Description B - Unclear open
Unclear Yes Yes Yes
not reported 24.6%
Jarratt 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Computer generated list Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Unclear N: 142 TD: 4 wks; FU: 6 wks LF: 1 (0.7%) BC: Yes Age: 45.1 (15.37SD)
125
Participants
Jarratt 2004
(Continued)
Gender (%M): 42.3% Severity: TSS (0 to 9): 6.6 GSS ( 6 pt (rescaled: 0 = very severe; 5 = clear): 1.65 (0.61SD), N = 142 INCLUSION CRITERIA Aged 12 or over; moderate to severe scalp psoriasis (global severity score 3); compliance with washout periods for systemic therapies (details not reported) EXCLUSION CRITERIA Pregnancy or risk thereof; known allergy to test products; need for systemic therapy or other concomitant antipsoriatics; excessive UV exposure Interventions Clobetasol propionate shampoo, 0.05%, OLUX OD (C) Placebo shampoo, OD (P) Treatments applied OD, left to dry for 15 minutes, then washed out Placebo represented by vehicle for clobetasol propionate Global severity score (GSS) (6 pt: 0 = clear to 5 = very severe) Total severity score (erythema, thickening, scaling) (TSS) (0 to 9) Individual sign scores for erythema, thickening, scaling pruritis, % scalp involvement (4 pt: 0 = none to 3 = severe) IAGI (5 pt: worse to clear) PAGI (5 pt: worse to clear) Sponsored by Galderma R&D Inc Missing date imputed using last observation carried forward No case of skin atrophy, teleangiectasia or acne reported Scalp trial SD imputation (TSS)
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double- blind (patient / investigator)
Yes Yes Yes Yes
126
Jekler 1992 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 30 TD: 8 wks LF: 3 (10%) BC: Not reported Age: 45.2 (14.0SD; N = 27) Gender (%M): 77.8%; N = 27 Severity: Duration disease (years): 20.5 (14.8SD; N = 27) Duration exacerbation (mths): 5.1 (6.4SD; N = 27) Severity (mean score, 0 to 3): 1.9; N = 27 INCLUSION CRITERIA Chronic plaque-type psoriasis with bilateral lesions of equal clinical severity; adult. EXCLUSION CRITERIA Topical or systemic corticosteroids; recent phototherapy. Dithranol 2% ointment one minute therapy, OD (D) Placebo (vehicle) (P) Severity: [pruritis; erythema; scaling; inltration; overall result] Investigators assessment of degree of clearing Patients assessment of degree of clearing: Sponsored by E Merck AB
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up?
Unclear Yes
not reported 10.0%
127
Jekler 1992
(Continued)
Yes Unclear not reported
Jin 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Not stated Concealment: unclear BLINDING Double-blind (patient/ investigator) WITHDRAWAL / DROPOUT Described N: 96 TD: 6 wks; FU: 6 wks LF: 7 (7.3%) BC: Yes Age: 35.8 (range: 18 to 65) Gender (%M): 57.3% Severity: TSS (0 to 20): 9.4 INCLUSION CRITERIA Chronic plaque psoriasis; aged over 18? (cannot translate) EXCLUSION CRITERIA (cannot translate) Anti IL-8 monoclonal antibody cream (M) Placebo (P) Efcacy rate Cure rate Erythema, inltration, scaling, pruritis TSS (skin damage, erythema, inltration, thickness, scaling) IAGI (4-pt: failure to cure) Sponsored by Biological Technical Medical Trade Limited
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment?
128
Jin 2001
(Continued)
Yes
Unclear Yes Yes Yes
not reported 7.3%
Jorizzo 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 89 TD: 4 wks; FU: 6 wks LF: Unclear BC: Yes Age: 49.7 (range: 21 to 84) Gender (%M): 65% Severity: Duration of psoriasis (range, years): 1 to 57 Duration of exacerbation (range, wks): 3 to 2080 % BSA affected: 8.1% INCLUSION CRITERIA Moderate to severe plaque type psoriasis. Nonhospitalised men or nonpregnant; nonlactating women 12 yrs; baseline morning serum cortisol concentration of 5 to 18 mcg/100mL. EXCLUSION CRITERIA Recent topical anti-psoriatic medication or other drug that could alter psoriatic status Clobetasol propionate emollient 0.05% BD (C) Placebo (vehicle) (P) Severity [erythema; skin thickening; scaling; pruritis] Total Severity Score (0 to 12) Investigator global assessment of improvement (6 pt: worse to cleared)
129
Participants
Interventions
Outcomes
Jorizzo 1997
(Continued)
Patient global assessment of improvement (5 pt: worse to excellent) Notes Sponsored by Glaxo Wellcome Inc. SD imputation (TSS)
Kang 1998 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: identical tubes with computer generated codes Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 30 TD: 6 wks LF: 0 (0%) BC: Psoriasis comparable, demographics unclear Age: 41 (range: 18 to 66) Gender (%M): 66.7% Severity: TSS(0 to 24): 12.27 INCLUSION CRITERIA Mild to moderate stable plaque-type psoriasis; adult. EXCLUSION CRITERIA Recent systemic therapy, UV or topical therapy for psoriasis (excluding emollient). Pregnant or breast-feeding women
130
Participants
Kang 1998
(Continued)
Interventions
Calcipotriene ointment 0.005%, BD (C) Placebo (vehicle) (P) Signs: [erythema; thickness; scaling] TSS (0 to 24) Investigator global assessment (7-pt: worse to clear) Sponsored with grants from Bristol-Myers Squibb Corporation and from Babcock Dermatologic Endowment (University of Michigan)
Outcomes
Notes
Yes Yes Yes Yes
computer generated 0.0%
partial
Kanzler 1993 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: identical containers labelled right and left; labelling method not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 18 TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Not reported Age: 45.4 (range: 21 to 66) Gender (%M): 55.6%
131
Participants
Kanzler 1993
(Continued)
Severity: not reported INCLUSION CRITERIA Bilaterally similar chronic stable plaque psoriasis. EXCLUSION CRITERIA Recent topical or systemic therapy. Interventions Tar (liquor carbonis detergens) 5%, BD (T) Placebo (vehicle) (P) Severity: [erythema; induration; scaling; pruritis] Total severity score (0 to 12) Investigator global assessment: % improvement from baseline, based on TSS Sponsorship not reported Compliance assessed by unused medication returned at each visit. Compliance rate for patients in each group > 90%. Scalp trial
Outcomes
Notes
132
Katz 1987a Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 40 TD: 12 wks; FU: 12 wks LF: 2 (5%) BC: Yes Age: 46.7 Gender (%M): 60% Severity: Duration (years): 20.8 % patients with BSA affected < 10%: 68% INCLUSION CRITERIA Plaques psoriasis in remission (> 85% resolution) after 2/3 weeks treatment with Betamethasone dipropionate Note: 38/59 (64%) achieved remission during the acute phase EXCLUSION CRITERIA Not achieving remission during acute phase treatment. Betamethasone dipropionate, intermittent maintenance (3 doses at 12 hour intervals each weekend) (B) Placebo (vehicle) (P) Signs: [erythema; induration; scaling] Area adjusted clinical score Relapse (adjusted clinical score > 35% of baseline score) Sponsorship: supported in part by a grant from Schering Plough Corporation SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
133
Katz 1987a
(Continued)
Unclear Yes Yes Yes
not reported 5.0%
Katz 1991a Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated code Concealment unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 94 TD: 24 wks; FU: 24 wks LF: 4 (4.3%) BC: Yes Age: 46.0 (range: 21 to 86) Gender (%M): 67.8% Severity: overall score not reported INCLUSION CRITERIA Plaques psoriasis in remission after 3/4 weeks treatment with Betamethasone dipropionate (erythema score = 1; induration = 0.5; scaling = 0) Note: 94/123 (76%) achieved remission during acute phase EXCLUSION CRITERIA Recent topical or systemic treatment; pregnant; nursing; intent to conceive; not achieving remission during acute phase treatment Betamethasone dipropionate, intermittent maintenance (3 doses at 12 hour intervals once a week) (B) Placebo (vehicle) (P) Signs: [erythema; induration; scaling] TSS (0 to 9) Area adjusted clinical score Treatment failure (Adjusted clinical score 2.5, or overall disease status moderate or severe) Overall disease status Patient evaluation of effectiveness. Time to relapse
134
Participants
Interventions
Outcomes
Katz 1991a
(Continued)
Sponsorship: not reported, but corresponding author employed by the Schering Corporation
Yes Yes Yes Yes
Katz 1991b Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: identical tubes labelled by computer generated code Concealment: Unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 110 TD: 2 wks LF: 2 (1.8%) BC: Inadequately reported Age: 51.7 (range: 19 to 84) Gender (%M): 80.6% Severity: Duration of disease (years): 21 (range 1 to 57) Duration of exacerbation (years): 15.4 (range < 1 to 57) Total severity score (0 to 12): median: 8 INCLUSION CRITERIA Comparable bilateral lesions of moderate or greater severity of plaque psoriasis; adult; at least 2 signs or symptoms of at least moderate severity; lesions 10cm EXCLUSION CRITERIA Pustular or erythodermic psoriasis; recent topical or systemic medication; women at risk of
135
Participants
Katz 1991b
(Continued)
pregnancy Interventions Halobetasol propionate cream, 0.05% BD (H) Placebo (vehicle) (P) Severity: (0 to 3) [erythema; plaque elevation; scaling pruritis] Total severity score (0 to 12) Patient global assessments of effectiveness and overall rating (5 pt: poor to excellent) Sponsorship: supported by an educational grant from Westwood-Squibb Pharmaceuticals, a Bristol-Myers Squibb company
Outcomes
Notes
Yes Yes Yes Unclear
not reported
Kaufmann 2002 (H) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated randomisation schedule Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 1603 TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Yes Age: 48.4 (range: 17 to 90)
136
Participants
Kaufmann 2002 (H)
(Continued)
Gender (%M): 60.5% Severity: PASI mean: 10.0 (range: 1.2 to 49.5) Duration: 19.2 (range: 0 to 75) INCLUSION CRITERIA Patients aged 18 and over with chronic plaque psoriasis; BSA at least 10% EXCLUSION CRITERIA Unstable psoriasis in treatment areas; other skin diseases that could confound treatment assessments; concomitant antipsoriatic therapy; hypercalcaemia; application of study corticosteroid to untargeted lesion; pregnancy; lactation Interventions Calcipotriol 50 mcg/g + betamethasone dipropionate 0.5 mg/g combination ointment, OD (D) Calcipotriol, 50 mcg/g, in combination vehicle ointment OD (C) Betamethasone dipropionate 0.5 mg/g, in combination vehicle ointment, OD (B) Placebo (combination vehicle) ointment, OD (P) PASI, modied (change score) Investigators global assessment of disease severity (6-pt: disease absent to very severe) Patients global assessment of disease severity (6 pt: worse to cleared) Sponsored by Leo Pharmaceuticals Compliance rates reported for each regimen
Outcomes
Notes
Yes Yes Yes Yes
137
Kaufmann 2002 (P) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated randomisation schedule Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 1603 TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Yes Age: 48.4 (range: 17 to 90) Gender (%M): 60.5% Severity: PASI mean: 10.0 (range: 1.2 to 49.5) Duration: 19.2 (range: 0 to 75) INCLUSION CRITERIA Patients aged 18 and over with chronic plaque psoriasis; BSA at least 10% EXCLUSION CRITERIA Unstable psoriasis in treatment areas; other skin diseases that could confound treatment assessments; concomitant antipsoriatic therapy; hypercalcaemia; application of study corticosteroid to untargeted lesion; pregnancy; lactation Calcipotriol 50 mcg/g + betamethasone dipropionate 0.5 mg/g combination ointment, OD (D) Calcipotriol, 50 mcg/g, in combination vehicle ointment OD (C) Betamethasone dipropionate 0.5 mg/g, in combination vehicle ointment, OD (B) Placebo (combination vehicle) ointment, OD (P) PASI, modied (change score) Investigators global assessment of disease severity (6-pt: disease absent to very severe) Patients global assessment of disease severity (6 pt: worse to cleared) Sponsored by Leo Pharmaceuticals Compliance rates reported for each regimen
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Authors judgement Unclear Yes Description B - Unclear double-blind (patient / assessor)
138
Kaufmann 2002 (P)
(Continued)
Yes Yes Yes Yes
Kim 1994 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (unclear who was blinded) WITHDRAWAL / DROPOUT Not described N: 10 TD: 8 wks; FU: 8 wks LF: 0 (0%) BC: Yes Age: 32.1 (range 20 to 52) Gender (%M): 60% Severity: PASI: 10.49 (1.60SD) Duration: 6.7 years (range 0.2 to 15) INCLUSION CRITERIA Psoriasis EXCLUSION CRITERIA Not identiable Calcipotriol ointment 50 mcg/g, BD (C) Desoxymethasone ointment 2.5 mg/g, BD (D) PASI Erythema, inltration, desquamation (0 to 9) Sponsorship not reported
Participants
Interventions
Outcomes
Authors judgement
Description
139
Kim 1994
(Continued)
Unclear Yes
B - Unclear double-blind (unclear who was blinded)
Unclear Yes Yes Yes
not reported 0.0%
Kiss 1996 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 239 TD: 8 wks LF: 29 (12.1%) BC: Not reported Age: not reported Gender (%M): not reported Severity: not reported INCLUSION CRITERIA Moderate scalp psoriasis; adult; overall disease severity 4 EXCLUSION CRITERIA None reported Calcipotriene solution 0.0025% and 0.005% BD (C) Placebo (vehicle) (P) Severity: [scaling; erythema; plaque elevation; pruritis] Overall severity (9 pt: none to v. severe) Investigator global assessment (4 pt: worsened to cleared)
Participants
Interventions
Outcomes
140
Kiss 1996
(Continued)
Notes
Sponsored by Bristol Myers Squibb Pharmaceuticals Carder 1996 reports nding for subgroup (N = 29) Scalp trial
Unclear Yes Unclear Unclear
not reported 12.1% not reported not reported
Klaber 1994 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 474 TD: 4 wks LF: Assessment: 6 (1.3%) TSS: 29 (6.1%) BC: Yes Age: 44.1 (range: 18 to 90) Gender (%M): 51.5% Severity: TSS (0 to 12): 6.5 (range: 2 to 12) Duration of scalp psoriasis (yrs): 13.1 (range: 0.1 to 67.0) INCLUSION CRITERIA Adults; stable, mild-to-moderate scalp psoriasis; history of psoriasis on body EXCLUSION CRITERIA
141
Participants
Klaber 1994
(Continued)
More extensive, severe or infected psoriasis; recent systemic antipsoriatic treatment or UV; concurrent vitamin D, calcium or other relevant medication; signicant hepatic or renal disease; hypercalcaemia; risk of pregnancy; pregnancy; lactation Interventions Calcipotriol solution 50 mcg/ml, BD (C) Betamethasone 17-valerate solution 1 mg/ml BD (B) Investigator global assessment (5-pt: worse to cleared) Patient global assessment (5-pt: worse to cleared) Total sign score [erythema, thickness, scaliness] (0 to 12) Assessment of extent of scalp psoriasis Assessment of acceptability Sponsored by Leo Pharmaceutical Products Scalp trial
Outcomes
Notes
Unclear Yes Yes Yes
not reported 1.3%
Klaber 2000b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described
142
Klaber 2000b
(Continued)
Participants
N: 475 TD: 8 wks; FU: 24 wks (N = 166) LF: 52 (10.9%) BC: Yes Age: 45.3 Gender (%M): 52.0% Severity: Total Severity Score (0 to 12): 5.1 INCLUSION CRITERIA Mild or moderate scalp psoriasis EXCLUSION CRITERIA Other forms of psoriasis; topical antipsoriatic treatment within previous two wks; systemic antipsoriatic treatment or UV therapy within previous four wks; concomitant vitamins, calcium or other medications that could affect the course of psoriasis; known hypersensitivity to study medications; pregnancy; inadequate contraception; lactation; hypercalaemia; signicant renal or hepatic disease Calcipotriol solution, 50 mcg/g, (Dovonex), BD (C) Coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ), OD (T) IAGI (6 pt: worse to cleared) TSS (0 to 12) Patients global assessment of disease severity (VAS) Sponsored by Leo Pharmaceuticals All patients who achieved at least a slight improvement in scalp psoriasis then received 16 weeks of treatment with calcipotriol BD Scalp trial
Interventions
Outcomes
Notes
Unclear Yes Yes Yes
not reported 10.9%
143
Kragballe 1988b Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 30 TD: 6 wks LF: 3 (10%) BC: Yes Age: 39 (range: 18 to 65) Gender (%M): 30.0% Severity: Duration (yrs): 15.3 (range: 1 to 35) TSS (0 to 9): 6.9 % BSA: 18.7% (range: 12 to 50%) INCLUSION CRITERIA Stable symmetrically distributed moderate; chronic plaque-type psoriasis; outpatients; adult. Women above child bearing age or using adequate contraception. EXCLUSION CRITERIA Recent topical, systemic, intralesional or UV radiation therapy (excluding bland emollients) ; non-normal serum levels of calcium and creatinine; taking calcium tablets Calcipotriol cream, 10 mcg/g, 33 mcg/g or 100 mcg/g, BD C(10); C(33); C(100) Placebo (vehicle) (P) Severity: [erythema; thickness; scaling] TSS (0 to 9) Investigator global assessment (5-pt: worse to clear) Patient global assessment (5-pt: worse to clear) Sponsorship: not reported
Participants
Interventions
Outcomes
144
Kragballe 1988b
(Continued)
Unclear Yes Yes Yes
not reported 10.0%
Kragballe 1991a Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 345 TD: 6 wks LF: 3 (0.9%) BC: Yes Age: 45.2 (range: 18 to 90) Gender (%M): 58.8% Severity: PASI: 8.35 (range: 0.60 to 48.5) Duration (yrs): 19.5 (range: 0.5 to 76) INCLUSION CRITERIA Adult; symmetrical chronic plaque psoriasis; inpatients and outpatients EXCLUSION CRITERIA Unstable psoriasis; recent systemic or UV therapy; hypercalcaemia; impaired renal/ hepatic function; high dose calcium /Vitamin D intake; unresponsive to corticosteroids; concomitant medication Calcipotriol ointment, 50 mcg/g, BD (C) Betamethasone valerate ointment, 0.1%, BD (B) PASI Total sign score [erythema, thickness, scaliness] (0 to 12) Patient assessment of response Sponsored by Leo Pharmaceuticals Inpatients / outpatients SD imputation (TSS)
145
Participants
Interventions
Outcomes
Notes
Kragballe 1991a
(Continued)
Unclear Yes Yes Yes
not reported 0.9%
Kragballe 1998b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: not stated BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 699 TD: 8 wks; FU: 8 wks LF: 8 (1.1%) BC: Psoriasis comparable, demographics unclear Age: not stated Gender (%M): not stated Severity: not stated INCLUSION CRITERIA Adult; stable chronic plaque psoriasis on trunk and limbs EXCLUSION CRITERIA Pregnancy; risk of pregnancy; lactation; recent systemic or UV therapy; concomitant medication; hypercalcaemia or renal disease; planned exposure to sun Calcipotriol cream, 50 mcg/g BD (C2) Calcipotriol cream, 50 mcg/g OM plus clobetasone17-butyrate cream, 0.5 mg/g ON (CL) Calcipotriol cream, 50 mcg/g OM plus betamethasone 17-valerate cream, 1 mg/g ON (CB) Calcipotriol cream, 50 mcg/g OM plus vehicle ON (C1)
146
Participants
Interventions
Kragballe 1998b
(Continued)
Outcomes
PASI Investigator overall assessment of response (6 pt: worse to clearance) Patient overall assessment of response (6 pt: worse to clearance) Sponsored by Leo Pharmaceuticals
Unclear Yes Unclear Yes
not reported 1.1% not reported partial
Kragballe 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Computer generated randomization schedule, using centralized telephone voice response system Concealment: Adequate BLINDING Double-blind (patient / investigator) (Groups A and B) Single-blind (investigator) (Group C) WITHDRAWAL / DROPOUT Described N: 972 TD: 8 wk; FU: 12 wks LF: 99 (10.2%) BC: Yes Age: 47.7 (range: 18 to 97) Gender (%M): 63.8% Severity: Duration (yrs): 18.5 (range: 0 to 70) PASI: 10.5 (range: 2 to 49)
147
Participants
Kragballe 2004
(Continued)
% with moderate disease: 64.3% INCLUSION CRITERIA Aged 18 and over; chronic plaque psoriasis amenable to topical treatment; BSA 10% of at least one body region (arms, trunk, legs) EXCLUSION CRITERIA Pregnancy or risk thereof; lactation; unstable psoriasis or other inammatory skin disease; concurrent systemic or UV therapy; concurrent topical therapy for trunk or limbs; abnormal calcium homeostasis Interventions TCP OD for 8 wks then: calcipotriol ointment 50 mcg/g OD for 4 wks (A) TCP OD for 4 wks then: calcipotriol ointment 50 mcg/g OD (weekdays) and TCP OD (weekends) for 8 wks (B) Calcipotriol ointment 50 mcg/g BD for 12 wks (C) TCP: 2 compound product: calcipotriol ointment 50 mcg/g, plus betamethasone dipropionate 0.5 mg/g ointment PASI Investigators global assessment of severity (PGA) (6pt: absence of disease to very severe disease) Self reported compliance with trial medication Sponsored by Leo Pharmaceuticals Request data: none supplied Reversible skin atrophy: A: 1/322; B: 0/322; C: 0/327
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Authors judgement Yes Yes Description A - Adequate double-blind (patient / investigator) (Groups A and B) single-blind (investigator) (Group C) computer-generated 10.2%
Yes Yes Yes Yes
148
Krueger 1998 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 45 TD: 6 wks LF: 0 (0%) BC: Reported to be similar Age: 50 (range: 23 to 83) Gender (%M): 84% Severity: not reported INCLUSION CRITERIA Mild to moderate bilateral psoriatic plaques; adult; total severity score ?6. EXCLUSION CRITERIA Pregnant; nursing or of likely to conceive; recent use of certain topical agents; recent systemic retinoids, UV phototherapy or systemic anti psoriasis drugs Tazarotene gel 0.01% or 0.05% BD (T) Placebo (vehicle) (P) Severity: [erythema; plaque elevation; scaling] TSS (0 to 12) Investigator global assessment (6 pt: no change/worse to completely clear) Sponsored by Allergan, Inc, California
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments?
Unclear Yes Yes
149
Krueger 1998
(Continued)
Yes
Kse 1997 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Unclear WITHDRAWAL / DROPOUT Described N: 43 TD: 10 days FU: 20 days LF: 0 (0%) BC: Yes Age: not stated Gender (%M): not stated Severity: not stated INCLUSION CRITERIA Psoriasis of the scalp EXCLUSION CRITERIA Not reported Calcipotriol ointment 50 mcg/g, occluded, ON (CO) Clobetasol 17-propionate solution BD (CP) TSS (0 to 9) Sponsorship not reported Scalp trial
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Authors judgement Unclear Unclear Description B - Unclear not reported
Unclear Yes
not reported 0.0%

150
Kse 1997
(Continued)
Unclear Yes
not reported
Landi 1993 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Unclear WITHDRAWAL / DROPOUT Described N: 40 TD: 6 wks; FU: 10 wks LF: 0 (0%) BC: Psoriasis comparable, demographics unclear Age: range: 17 to 84 Gender (%M): not stated Severity: PASI: mean: 11.6 (range: 3.0 to 35.1) INCLUSION CRITERIA Adult; mild and moderate psoriasis EXCLUSION CRITERIA Not reported Calcipotriol ointment, 50 mcg/g, BD (C) Clobetasol propionate 0.05% ointment, BD (CP) PASI Sponsored by Leo Pharmaceuticals Landi, 1993 reports the ndings of a single centre, one of three centres reported in Landi et al, 1993 (N = 120)
Participants
Interventions
Outcomes Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Authors judgement Yes Unclear Description A - Adequate not reported
151
Landi 1993
(Continued)
Unclear Yes Yes Yes
Lane 1983 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 157 TD: 3 wks; FU: 3 wks LF: 18 (11.5%) BC: Yes Age: 39.6 Gender (%M): 52.5% Severity: TSS (0 to 20): 10.6 INCLUSION CRITERIA History and physical nding compatible with psoriasis including scaling erythema, epidermal thickening and/or crusting; all ages >1 year; stable disease. EXCLUSION CRITERIA Recent topical or systemic corticosteroid treatment; oral antihistamine; antipruritic therapy, UV or X-ray therapy or any medication affecting the study; pregnant Betamethasone dipropionate ointment, 0.05% OD (B) Diorasone diacetate ointment, 0.05% OD (D) Placebo (vehicle) (P) Severity: [scaling; erythema; pruritis; thickening; crusting; overall condition] Total severity score (0 to 20) Sponsorship not reported SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias
152
Lane 1983
(Continued)
Unclear Yes Yes Yes
not reported 11.5%
Langner 1992 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: Unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 29 TD: 6 wks; FU: 6 wks LF: 0 (0%) BC: Yes Age: mean: 40.5 (range: 16-77) Gender (%M): 69.0% Severity: not reported INCLUSION CRITERIA Severe chronic psoriasis; symmetrical lesions; adult; outpatients EXCLUSION CRITERIA Pregnancy or inadequate contraception. Calcitriol ointment, 3 mcg/g BD (C) Placebo (vehicle) (P) Severity: [erythema; pustules, desquamation, encrustation, vesiculation and pruritis] Investigator global assessment (6 pt: worse to clear)
Participants
Interventions
Outcomes
153
Langner 1992
(Continued)
Notes
Sponsorship not reported All patients received two weeks pre-treatment with vehicle BD
Unclear Yes Yes Yes
not reported 0.0% partial yes
Langner 1993 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 32 TD: 6 wks; FU: 6 wks LF: 2 (6.3%) BC: Yes Age: mean: 42.4 (range: 16 to 77) Gender (%M): 62.5% Severity: global severity score (0 to 4): 3.5 INCLUSION CRITERIA Bilateral; symmetrical; severe chronic plaque psoriasis; outpatients. EXCLUSION CRITERIA Pregnancy or inadequate contraception. Use of calcium; vitamin D or analogues; calciumcontaining antacids; digitalis; thiazide diuretics or glucocorticosteroids
Participants
154
Langner 1993
(Continued)
Interventions
Calcitriol ointment 15 mcg/g BD (C) Placebo (vehicle) (P) Severity: [erythema; scaling; induration; pruritis] PASI Investigator global assessment (6 pt: worse to clear) Sponsorship not reported All patients received two weeks pre-treatment with vehicle BD
Outcomes
Notes
Unclear Yes Yes Yes
not reported 6.3%
Langner 2001 (H) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 44 TD: 6 wks; FU: 6 wks (14 wks for responders) LF: 4 (9.1%) BC: not reported Age: not reported Gender (%M): 54.5% Severity: not reported
155
Participants
Langner 2001 (H)
(Continued)
INCLUSION CRITERIA Adults with chronic plaque psoriasis; BSA = 20% EXCLUSION CRITERIA Pregnancy; inadequate contraception Interventions Calcitriol ointment, 3 mcg/g, BD (C) Betamethasone valerate ointment, 0.1%, BD (B) IAGI (5 pt: worse to clearance) Sponsorship not reported All patients received two weeks pre-treatment with vehicle BD
Outcomes Notes
Langner 2001 (P) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Unclear Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 44 TD: 6 wks; FU: 6 wks (14 wks for responders) LF: 4 (9.1%) BC: not reported
156
Participants
Langner 2001 (P)
(Continued)
Age: not reported Gender (%M): 54.5% Severity: not reported INCLUSION CRITERIA Adults with chronic plaque psoriasis; BSA = 20% EXCLUSION CRITERIA Pregnancy; inadequate contraception Interventions Calcitriol ointment, 3 mcg/g, BD (C) Placebo ointment, BD (P) IAGI (5 pt: worse to clearance) Sponsorship not reported All patients received two weeks pre-treatment with vehicle BD
Outcomes Notes
Lassus 1991 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Block randomisation Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
157
Lassus 1991
(Continued)
Participants
N: 50 TD: 12 wks; FU: 12 wks LF: 8 (16%) BC: Yes Age: 42.8 (range: 22 to 50; N = 42) Gender (%M): 45.2% (N = 42) Severity: TSS (0 to 12): 7.72 INCLUSION CRITERIA Stable psoriasis of at least one years duration; mild to moderate plaque psoriasis; nummular, discoid or guttate psoriasis; stable aged 18 to 50; localised lesions EXCLUSION CRITERIA Pregnancy; lactation; antipsoriatic therapy within previous two wks; patients declining to abstain from alcohol during treatment period Oleum horwathiensis (Psoricur), OD (O) Placebo, OD (P) TSS (0 to 12): Severity: [scaling, pruritis, erythema, induration] IAGI (5 pt: poor to healed) Sponsorship: not reported SD imputation (TSS)
Interventions
Outcomes
Notes
Yes Yes Yes Yes
block 16.0%
158
Lebwohl 2002 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported (but ratio 3:1 used) Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 81 TD: 2 wks; FU: 4 wks LF: 5 (6.2%) BC: Yes Age: not reported Gender (%M): not reported Severity: pruritis (0 to 4): 2.11 INCLUSION CRITERIA Mild to moderate plaque type psoriasis; aged at least 18; TSS (0 to 12) 3; target lesions in at least one of 5 anatomical regions; BSA 20% EXCLUSION CRITERIA Investigational medication within previous four wks; topical antipsoriatic treatment within previous two wks; systemic antipsoriatic treatment within previous four wks; concurrent UV treatment or sunbathing; pregnancy; lactation; inadequate contraception; men wishing to father children during the study; concurrent drug or alcohol abuse Clobetasol propionate foam, 0.05%, BD (maximum of 50 g/wk) (C) Placebo foam, BD (P) IAGI (7 pt: worse to completely clear) PAGI (7 pt: worse to completely clear) Total severity score: erythema, scaling, thickness, pruritis (0 to 4) Adverse events Medicines consumption (compliance) Sponsored by Connetics Corporation Only non-scalp sites treated
Participants
Interventions
Outcomes
Notes
159
Lebwohl 2002
(Continued)
Unclear Yes Yes Yes
Lebwohl 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 167 TD: 8 wks; FU: 8 wks LF: 30 (18%) BC: Yes Age: 48.0 Gender (%M): 58.7% Severity: SSS (0 to 6) (median): 3 (range: 1.5 to 5.0); % with concurrent plaque-type lesions: 85% INCLUSION CRITERIA Age limit unclear (stated as 2 and 16); chronic plaque psoriasis affecting intertriginous and facial skin; disease stable or slowly worsening for 1 wk; target lesion of moderate erythema and TSS (0 to 12) 4 EXCLUSION CRITERIA Systemic therapy or phototherapy within previous four wks; topical therapy within previous two wks; inhaled / intranasal corticosteroids within previous two wks; other topical agents (excluding sunscreen) within previous one dy; recently diagnosed (< six mths) or recent exacerbation of inverse psoriasis; uncontrolled chronic co-morbidity; pregnancy; lactation; previous use of tacrolimus ointment for facial or intertriginous psoriasis Tacrolimus ointment 0.1%, BD Placebo ointment, BD Inverse psoriasis severity score (Static Severity Score) (SSS) (6 pt: clear to very severe) IAGI (PGA)(7 pt: exacerbation to clear) Signs (0 to 3 each) (erythema, induration, desquamation; overall severity) Patient satisfaction (% agreeing with range of statements)
160
Participants
Interventions
Outcomes
Lebwohl 2004
(Continued)
Notes
Sponsored by Fujisawa Healthcare Inc Loss to follow up reported as 11/167 Non-study body sites received usual topical treatment No adequate effectiveness data reported or available from sponsor Inverse psoriasis
Unclear Yes Yes Yes
not reported 18.0%
Lepaw 1978 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: predetermined schedule using identical containers coded with patient number Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 29 TD: 2 wks; FU: 2 wks LF: 2 (6.9%) BC: Inadequately reported Age: 14 to 75 Gender (%M): 55.2% Severity: not reported IN CLUSION CRITERIA Bilaterally similar psoriatic lesions of the scalp; adults or adolescents EXCLUSION CRITERIA
161
Participants
Lepaw 1978
(Continued)
Systemic therapy, topical scalp treatments Interventions Halcinonide solution 0.1%, TDS (H) Placebo (vehicle), TDS (P) Overall therapeutic response Overall comparative response Sponsorship not reported Scalp trial
Outcomes
Notes
Lister 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 171 TD: 8 wks; FU: 16 wks LF: not reported BC: Psoriasis comparable, demographics unclear Age: not stated Gender (%M): not stated
162
Participants
Lister 1997
(Continued)
Severity: TSS (scale NR): 6.24 INCLUSION CRITERIA Chronic plaque psoriasis EXCLUSION CRITERIA Unclear Interventions Dithranol cream 1 to 3%, OD (D) Calcipotriol, BD (C) Total sign score: [erythema, scaling, induration] (scale NR) Investigator and patient global assessments (scales NR) Relapse rates Sponsored by Bioglan Laboratories
Outcomes
Description B - Unclear single-blind (investigator)
not reported not reported partial partial
Medansky 1987 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
163
Medansky 1987
(Continued)
Participants
N: 121 TD: 3 wks; FU: 3 wks LF: 6 (5.0%) BC: Yes, except duration of disease (p = 0.04) Age: 53.8 (range: 16 to 80) Gender (%M): 67.8% Severity: Duration (yrs): 17.9 (range: 1 to 52) TSS (0 to 9): 6.6 INCLUSION CRITERIA Aged 12; chronic plaque psoriasis, stable or worsening; duration 1 year; Total Sign Score 6 EXCLUSION CRITERIA Concomitant medication; recent systemic corticosteroids or antimetabolites; recent topical corticosteroids; pregnancy; lactation, those needing > 90 g/wk topical steroid, other forms of psoriasis Mometasone furoate ointment, 0.1% OD (M) Vehicle OD (P) Signs: [erythema; induration; scaling] Total sign score (0 to 9) Investigator global assessment (6 pt: no change or worse to cleared or marked improvement) Supported in part by a grant from Schering Corporation SD imputation (TSS)
Interventions
Outcomes
Notes
Unclear Yes Yes Yes
not reported 67.8%
partial
164
Medansky 1996 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: schedule Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 134 TD: 3 wks; FU: 3 wks LF: 6 (4.5%) BC: unclear Age: 47 (range: 20 to 81) Gender (%M): not stated Severity: TSS(0 to 9): 6.5 % unstable psoriasis: 28% INCLUSION CRITERIA Mild-to-moderate symmetrical chronic plaque psoriasis; adult; TSS (0 to 9) 6 EXCLUSION CRITERIA Recent topical or systemic antipsoriatic therapy; recent lithium, NSAIDs or beta-blockers Diorasone diacetate ointment, 0.05%, BD (D) Calcipotriene ointment 0.005%, BD (C) Signs: [erythema, scaling, induration] Total sign score (0 to 9) Physician overall evaluation (7 pt: worse to clear) Physician comparative evaluation Patient comparative evaluation Sponsored by Dermik Laboratories Inc. Adverse events: itching and burning SD imputation (TSS/IAGI)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / assessor)
Unclear
not reported
165
Medansky 1996
(Continued)
Yes Yes Unclear
4.5% partial not reported
Molin 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 421 TD: 8 wks; FU: 8 wks LF: 4 (1%) BC: Psoriasis comparable, demographics not reported Age: not stated Gender (%M): not stated Severity: no summary measure reported INCLUSION CRITERIA Adult outpatients; mild-to-moderate stable and chronic plaque psoriasis of limbs and trunk EXCLUSION CRITERIA None reported Calcipotriol cream 50 mcg/g, BD (C) Betamethasone 17-valerate cream, 1 mg/g, BD (B) PASI (0 to 64.8) Severity scores Investigator global assessment of response (5 pt: worse to cleared) Patient global assessments of response (5 pt: worse to cleared) Sponsored by Leo Pharmaceutical Products
Participants
Interventions
Outcomes
166
Molin 1997
(Continued)
Yes
double-blind (patient / assessor)
not reported 1.0% not reported partial
Monastirli 2000 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 70 TD: 10 wks; FU: 10 wks LF: Not reported BC: Yes Age: 45.7 Gender (%M): 57.1% Severity: Duration (yrs): 17 PASI D: 7.31 (1.79SD, N = 35) C: 6.29 (1.63SD, N = 35) INCLUSION CRITERIA Inpatients with chronic plaque psoriasis EXCLUSION CRITERIA Pregnancy; lactation; ineffective contraception; systemic treatment within previous two mths; hepatic or renal disease; hypercalcaemia; known hypersensitivity to study medications Dithranol, 2%, 30 minutes OD (D) Calcipotriol ointment, 50 mcg/g, BD (C) PASI (excluding head)
Participants
Interventions
Outcomes
167
Monastirli 2000
(Continued)
Notes
Sponsorship not reported Inpatient treatment
Mortensen 1993b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 34 TD: 3 wks; FU: 4 wks LF: 0 (0%) BC: Psoriasis comparable, demographics inadequately reported. Age: 43 (range: 26 to 75) Gender (%M): 58.8% Severity: PASI: 12.2 INCLUSION CRITERIA Stable plaque-type psoriasis; adult outpatients; normal hepatic and renal function. EXCLUSION CRITERIA Recent UV or other psoriasis treatments; disease or medication inuencing calcium or bone metabolism
Participants
168
Mortensen 1993b
(Continued)
Interventions
Calcipotriol ointment 50 mcg/g BD (C) [max. 100 g/wk] Placebo (vehicle) (P) PASI Investigator global assessment: % improvement from baseline, based on PASI Patient global assessment: % improvement from baseline, based on PASI Sponsored by Leo Pharmaceuticals, Denmark
Outcomes
Unclear Yes Yes Yes
not reported 0.0%
partial
Olsen 1991 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 378 TD: 2 wks; FU: 3 wks LF: 1 (0.3%) BC: Yes Age: 46 (range: 18 to 88) Gender (%M): 45% Severity: Duration (yr): 12.0 (9.7SD, N = 377); range: 0.4 to 55.0
169
Participants
Olsen 1991
(Continued)
Severity: 80% moderate (6 TSS < 7.5): 20% severe (TSS > 7.5) INCLUSION CRITERIA Moderate to severe scalp psoriasis (TSS (0 to 9) 6); stable or worsening; adult. EXCLUSION CRITERIA Recent systemic, topical or UV treatment for psoriasis. Interventions Clobetasol propionate 0.05% BD (C) Placebo (vehicle) (P) Severity: [erythema; induration; scaling, pruritis] TSS (0 to12) Investigator global assessment (6 pt: worse to cleared) Patient global assessment (4 pt: poor to excellent) Sponsored in part by Glaxo Inc. Scalp trial SD imputation (TSS)
Outcomes
Notes
Unclear Yes Yes Yes
not reported 0.3%
170
Olsen 1996 (1) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described (for both trials together) N: 181 TD: 4 wks; FU: 4 wks LF: 3 (1.7%) BC: Yes Age: 49 (range: 15 to 76) Gender (%M): 68.0% Severity: Duration (yrs): 19 (range: 1 to 60) %BSA affected: 12.0% (range: 1 to 80%) %BSA treated: 11% (range: 1 to 80%) Fluticasone propionate 0.005% ointment (F) (max. 100 g/wk) Placebo (vehicle) (P) Investigator global assessment (6 pt: cleared to worse) Severity: [erythema; induration; scaling; pruritis] Patient subjective assessment [treatment effect: 1 = excellent to 4 = poor] Sponsorship not reported
Participants
Interventions
Outcomes
Unclear Yes Yes Yes
not reported 1.7%
171
Olsen 1996 (2) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described (for both trials together) N: 207 TD: 4 wks; FU: 4 wks LF: 2 (1.0%) BC: Yes Age: 45 (range: 12 to 87) Gender (%M): 52.7% Severity: Duration (yrs): 16 (range: 0.8 to 52) %BSA affected: 12.5% (range: 1 to 80%) %BSA treated: 12% (range: 1 to 80%) Fluticasone propionate 0.005% ointment (F) (max. 100 g/wk) Placebo (vehicle) (P) Investigator global assessment (6 pt: cleared to worse) Severity: [erythema; induration; scaling; pruritis] Patient subjective assessment [treatment effect: 1 = excellent to 4 = poor] Sponsorship not reported
Participants
Interventions
Outcomes
Unclear Yes Yes Yes
not reported 1.0%
172
Oranje 1997 Methods DESIGN Between patient Patient / parent delivery ALLOCATION Random Method of randomisation: computer generated random number table used by 7/14 centres to randomly select 3 patients Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 77 TD: 8 wks; FU: 8 wks LF: 0 (0%) BC: Yes Age: 10 (range: 2 to 14) Gender (%M): 46.8% Severity: Not reported INCLUSION CRITERIA Mild to moderate chronic plaque psoriasis; children aged 2 to 14. EXCLUSION CRITERIA Acute guttate; pustular, erythrodermic or worsening psoriasis; psoriasis mainly on the face; scalp or diaper area; systemic treatment; recent phototherapy; concurrent Vitamin D, calcium or other intercurrent medication; renal; hepatic or osteoarthritic disease Calcipotriol ointment, 50 mcg/g BD (C) Placebo (vehicle) (P) PASI: Severity: [redness; thickness; scaliness, area] Extent of disease Investigator global assessment Patient global assessment (by parent / guardian for those aged < 8) Compliance Sponsored by Leo Pharmaceutical Products, Denmark Children
Participants
Interventions
Outcomes
Notes
173
Oranje 1997
(Continued)
Yes Yes Yes Yes
computer-generated 0.0% partial
Ormerod 1997 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 12 TD: 2 wks; FU: 2 wks LF: unclear BC: unclear Age: not reported Gender (%M): not reported Severity: TSS (0 to 24): 12.2 INCLUSION CRITERIA Bilaterally similar chronic; stable plaque psoriasis. EXCLUSION CRITERIA Recent systemic or UV therapy Betamethasone valerate ointment, 0.1% BD (B) White soft parafn, BD (P) Signs:[erythema; elevation; scaling] Total sign score (0 to 24) Sponsored by Wyeth-Ayerst Research and Glaxo Dermatology
Participants
Interventions
Outcomes
174
Ormerod 1997
(Continued)
Yes
Unclear Unclear Yes Unclear
not reported not reported partial not reported
Ormerod 2000 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 17 TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Not reported Age: not reported Gender (%M): not reported Severity: TSS (0 to 24): 15.5 (SD: 3.7; N = 17) INCLUSION CRITERIA Stable plaque psoriasis EXCLUSION CRITERIA Pregnancy; ineffective contraception; lactation NG-monomethyl-L-arginine (L-NMMA) cream, 25%, BD NG-monomethyl-L-arginine (L-NMMA) cream, 5%, BD Placebo (P) TSS (elevation, erythema, scaling) (0 to 24) Sponsorship: not reported
Participants
Interventions
Outcomes Notes Risk of bias
175
Ormerod 2000
(Continued)
Ormerod 2005 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: randomised in blocks of four by the pharmacy department using Minitab Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Unclear N: 24 TD: 12 wks; FU: 12 wks LF: 2 (8.3%) BC: Yes Age: 47.5 (range: 28 to 78) Gender (%M): 75.0% Severity: TSS (0 to 24): 17.0 (3.3SD, N = 22) INCLUSION CRITERIA Chronic plaque psoriasis; aged 18 and over; no signicant co morbidity; transminase levels within double normal upper limit; EXCLUSION CRITERIA Planned exposure to sunlight over trial duration; pregnancy, or risk thereof; lactation; systemic or UV therapy within previous four wks; topical therapy within previous two wks; known allergy to macrolide drugs; renal or hepatic disease; renal malignancy within previous ve yrs;
Participants
176
Ormerod 2005
(Continued)
Interventions
Topical sirolimus, 2.2% for 6 wks then 8% for a further 6 wks (S) Placebo (P) Dosing frequency not reported Total Sign Score (TSS) of target plaque (erythema, thickening, scaling)(0 to 24) Sponsored by Wyeth Research, Philadelphia No systemic adverse event was considered clinically signicant Daily dosing frequency unclear
Outcomes Notes
Yes Yes Yes Yes
block 9.3%
Ortonne 1994 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Patients allocated sequentially upon inclusion Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 188 TD: 6 wks; FU: 6 wks LF: 32 (17.0%) BC: Yes Age: 46.0 (range: 20 to 85) Gender (%M) 67.3% Severity:
177
Participants
Ortonne 1994
(Continued)
Duration (yrs): 14.9 %BSA: 18.9% PASI: 11.67 % unstable psoriasis: 40% INCLUSION CRITERIA Chronic plaque psoriasis; stable or worsening; BSA 10 to 40%; PASI 1 to 30; outpatients EXCLUSION CRITERIA Pregnancy; lactation; concurrent disease; concomitant therapy; hypersensitivity to Vitamin D or analogues; planned exposure to sun Interventions Calcipotriol ointment, BD (C) Calcipotriol ointment OM, plus Betamethasone dipropionate ointment ON (CB) PASI Investigator global assessment Sponsored by Leo Pharmaceuticals
Outcomes
Yes Yes Yes Yes
sequential 17.0%
178
Ortonne 2003 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: Computer generated randomisation by blocks of four using RANUNI routine of the SAS system. Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 75 TD: 6 wks; FU: 6 wks LF: 10 (13.3%) BC: Yes, within patient design but comparability of lesions at baseline not reported Age: 44.5 (14.5SD: range: 18.8 to 70.7) Gender (%M): 53% Severity: not reported INCLUSION CRITERIA Patients with stable chronic plaque psoriasis, localised on sensitive areas: face, hairline, retroauricular and exural areas; aged 18 to 70; one to four bilateral lesions of similar severity EXCLUSION CRITERIA Pregnancy or risk thereof; lactation; concomitant disease; acute guttate, pustular, erythrodermic or arthropathic psoriasis; history of hypercalcaemia, renal dysfunction; calcium based calculi, conditions requiring systemic supplements of vitamin D or calcium; previous topical therapy within previous 2 wks (4 wks for retinoids); previous systemic therapy within previous 4 wks (16 wks for retinoids) Calcitriol ointment 3 mcg/g BD (C1) Calcipotriol ointment 50 mcg/g BD (C2) Investigators Global Assessment of local safety for each lesion (3 pt: 0: poor to 2: excellent) Mean of worst sign scores (0 to 9) (signs: perilesional erythema; perilesional oedema; stinging / burning) Investigators Global Assessment of Improvement (IAGI) (7 pt: worse to clear) Patients preference for tolerance, efcacy and global preference (5 pt: RHS > LHS: -2 to LHS > RHS: 2) Sponsorship not reported, but two authors work for Galderma, France inverse psoriasis SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
179
Ortonne 2003
(Continued)
Yes
single-blind (investigator)
Yes Yes Yes Yes
computer-generated block 13.3% partial partial
Ortonne 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Computer generated randomisation schedule Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 501 TD: 8 wks; FU: 8 wks LF: 21 (4.2%) BC: Yes Age: 51.2 (15.0SD, N = 501) Gender (%M): 54.9% Severity: PASI: 9.8 (6.1SD, N = 501) Duration (yrs): 19.4 (14.6SD, N = 501) INCLUSION CRITERIA Stable chronic plaque psoriasis amenable to topical treatment; aged 18 and over EXCLUSION CRITERIA Pregnancy or risk thereof; lactation; unstable psoriasis or other inammatory diseases; abnormality of calcium metabolism or hypercalcaemia; systemic or phototherapy within previous four wks; topical therapy within previous two wks; other topical therapy for trunk or limbs during study period; corticosteroid treatment of scalp (WHO: class IV) or facial area (WHO: class III/IV) during study period TCP ointment ON for 4 wks then: calcipotriol ointment 50 mcg/g ON for 4 wks (A) Tacalcitol ointment 4 mcg/g ON for 8 wks (T) TCP: two compound product: calcipotriol 50 mcg/g, plus betamethasone dipropionate 0.5 mg/g ointment
180
Participants
Interventions
Ortonne 2004
(Continued)
Outcomes
PASI: mean % reduction IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Sponsored by Leo Pharmaceutical Products
Yes Yes Yes Yes
Papp 2003 (H) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated random code Concealment: Adequate BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 1043 TD: 4 wks; FU: 4 wks LF: 15 (1.4%) BC: Yes Age: 47.1 Gender (%M): 58.4% Severity: mean PASI: 10.8 (range: 1 to 36) Duration: 18.7 years INCLUSION CRITERIA Chronic plaque psoriasis; aged at least 18; BSA 10%
181
Participants
Papp 2003 (H)
(Continued)
EXCLUSION CRITERIA Other types of psoriasis or skin diseases; hypercalcaemia; systemic antipsoriatic treatment or UV therapy within previous six wks; topical antipsoriatic therapy within previous two wks; other concomitant medication that might affect psoriasis; contraindications for corticosteroid treatment; planned exposure to UV light; pregnancy; lactation Interventions Calcipotriol 50 mcg/g + betamethasone dipropionate 0.5 mg/g combination ointment, BD (D) Calcipotriol, 50 mcg/g, in combination vehicle ointment BD (C) Betamethasone dipropionate 0.5 mg/g, in combination vehicle ointment, BD (B) Placebo (combination vehicle) ointment, BD (P) PASI (head excluded) Total severity score (9 pt, absent to very severe) IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Sponsored by Leo Pharmaceuticals
Outcomes
Yes Yes Yes Yes
182
Papp 2003 (P) Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer generated random code Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 1043 TD: 4 wks; FU: 4 wks LF: 15 (1.4%) BC: Yes Age: 47.1 Gender (%M): 58.4% Severity: mean PASI: 10.8 (range: 1 to 36) Duration: 18.7 years INCLUSION CRITERIA Chronic plaque psoriasis; aged at least 18; BSA 10%; EXCLUSION CRITERIA Other types of psoriasis or skin diseases; hypercalcaemia; systemic antipsoriatic treatment or UV therapy within previous six wks; topical antipsoriatic therapy within previous two wks; other concomitant medication that might affect psoriasis; contraindications for corticosteroid treatment; planned exposure to UV light; pregnancy; lactation Calcipotriol 50 mcg/g + betamethasone dipropionate 0.5 mg/g combination ointment, BD (D) Calcipotriol, 50 mcg/g, in combination vehicle ointment BD (C) Betamethasone dipropionate 0.5 mg/g, in combination vehicle ointment, BD (B) Placebo (combination vehicle) ointment, BD (P) PASI (head excluded) Total severity score (9 pt, absent to very severe) IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Sponsored by Leo Pharmaceuticals
Participants
Interventions
Outcomes
Authors judgement Yes
Description A - Adequate
183
Papp 2003 (P)
(Continued)
Yes
Yes Yes Yes Yes
Pariser 1996 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Not described N: 235 TD: 8 wks; FU: 8 wks LF: Unclear BC: Psoriasis comparable, demographics not reported. Age: 45.1 (range: 18 to 86) Gender (%M): not reported Severity: TSS (0 to 9): 4.75 INCLUSION CRITERIA Stable plaque-type psoriasis; otherwise healthy, non-pregnant patients; at least 4/9 for plaque elevation. BSA range: 5 to 20% EXCLUSION CRITERIA None reported Calcipotriene ointment, 0.005% OD (C) Placebo (vehicle) (P) Severity: [scaling; erythema; plaque elevation] TSS (0 to 9) Investigator global assessment (10 pt: ) Sponsored by Bristol-Myers Squibb Pharmaceutical Research Institute SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
184
Pariser 1996
(Continued)
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear Double-blind (patient / assessor)
Pauporte 2004 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 89 TD: 3 wks; FU: 4 wks LF: 4 (4.5%) BC: Yes Age: 46 (15SD) Gender (%M): 44.8% Severity: TSS (0 to 9): 7.15 INCLUSION CRITERIA Moderate to severe scalp psoriasis, stable or slowly exacerbating > 1 wk; aged 12; good general health; scalp involvement 20%; TSS (0 to 9) 6 EXCLUSION CRITERIA Pregnancy or risk thereof; lactation; patients requiring topical or systemic treatments that could affect psoriasis; systemic corticosteroids within previous 4wks;topical therapies within previous one wk; concomitant use of other scalp therapies
Participants
185
Pauporte 2004
(Continued)
Interventions
Fluocinolone acetonide 0.01% topical oil (Derma-Smoothe/FS), plus occlusion ON or for at least 4 hours (F) Placebo oil, plus occlusion ON or for at least 4 hours (P) Patients washed their hair with a non-medicated shampoo after treatment Total severity score (0 to 9) (erythema, thickening, scaling) Investigators assessment of global improvement (IAGI) (7 pt: cleared to exacerbation) Sponsorship not reported, but the corresponding author worked for Hill Dermaceuticals Inc, US To be eligible for inclusion in the efcacy analysis, patients were permitted to deviate from the treatment plan <= 2 consecutive days and <=4 /10 days No case of skin atrophy or telangiectasia reported Scalp trial
Outcomes
Notes
Unclear Yes Yes Yes
not reported 4.5%
Perez 1996 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
186
Perez 1996
(Continued)
Participants
N: 84 TD: 10 wks: FU: 52 wks LF: 0 (0%) BC: Yes Age: 46 (range: 19 to 76) Gender (%M): 65.5% Severity: TSS (0 to 9): 7.6? INCLUSION CRITERIA Stable plaque or erythrodermic psoriasis; unsatisfactory response to at least one previous treatment (topical steroids / UVB / PUVA / MTX); adult; BSA10% EXCLUSION CRITERIA Pregnant, nursing or inadequate contraception; hepatic or renal impairment; recent systemic therapy or phototherapy or topical medications (excluding emollients) Calcitriol, 1.5 mcg/g OD (C) Placebo (vehicle) (P) Severity: [erythema; plaque thickness; scaling] Total severity score (0 to 9) Investigator global assessment (5 pt, worse to excellent improvement) PASI (reported only for patients participating in follow up study) Supported by the NIH General Clinical Research Center Uncontrolled follow up study (N = 22) involving large area administration of Calcitriol. Twelve month results based on N = 6
Interventions
Outcomes
Notes
Unclear Yes Yes Yes
not reported 0.0%
187
Pinheiro 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 132 TD: 8 wks; FU: 8 wks LF: 10 (7.6%) BC: Yes Age: 48.2 (range: 17 to 90) Gender (%M): 59.1% Severity: Duration (yrs): 16.9 (range: 0.5 to 60) % severe: 13.6% INCLUSION CRITERIA Chronic plaque psoriasis; Adult; BSA 100 cm EXCLUSION CRITERIA Hypersensitivity to trial medications; concomitant treatment with Vitamin D/calcium/other relevant agent; pregnancy; risk of pregnancy; lactation; unable to comply with protocol Calcipotriol ointment, 50 mcg/g BD (C) Coal tar 5%/allantoin 2%/hydrocortisone cream 0.5% BD (T) Signs: [redness; thickness; scaliness] Total sign score (0 to 12) Investigator global assessment (5-pt: worse to cleared) Area of affected skin (area scales) Patient evaluation of overall response (VAS) Sponsored by Leo Pharmaceuticals SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Authors judgement Unclear No Description B - Unclear open
Unclear
not reported
188
Pinheiro 1997
(Continued)
Yes Yes Yes
7.6%
Reygagne 2002b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Not described N: 151 TD: 4 wks; FU: 4 wks LF: not reported BC: Yes (clinical only) Age: not reported Gender (%M): not reported Severity: TSS (0 to 9): 4.90 (1.74SD, N = 151) GSS (0 to 5): 3.50 (0.60SD, N = 151) INCLUSION CRITERIA Moderate to severe scalp psoriasis EXCLUSION CRITERIA Not reported Clobetasol propionate 17% 0.05% shampoo, OD (short contact: 15 minutes) (CL) Calcipotriol solution 0.005%, BD (CA) Total Severity Score (0 to 9) (erythema, desquamation, thickening) (TSS) Global severity score (0 to 5) (GSS) Sponsorship not reported, but two of the authors worked for Galderma R&D, France Abstract only Scalp trial
Participants
Interventions
Outcomes
Notes
189
Reygagne 2002b
(Continued)
Yes
single-blind (investigator)
Ruzicka 1998 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not stated Concealment: unclear BLINDING Double-blind (patient/ assessor) WITHDRAWAL / DROPOUT Described N: 178 TD: 2+4 wks; FU: 14 wks LF: 7 (3.9%) BC: Psoriasis comparable, demographics not reported Age: 42 (range: 18 to 80) Gender (%M): 55.6% Severity: PASI: 6.0 INCLUSION CRITERIA Adults; chronic plaque-type psoriasis; BSA 30%; calcium levels, renal and liver function within normal range EXCLUSION CRITERIA Pregnancy; lactation; recent systemic or UV therapy Calcipotriol 0.005% ointment BD, 6 weeks (C) Calcipotriol 0.005% ointment BD, 2 weeks, then Calcipotriol ointment 0.005% OM plus Betamethasone valerate ointment ON, 4 weeks (CB) PASI Investigator global assessment (6 pt: deterioration to complete healing): Patient evaluation of overall response (5 pt: scale NR) Sponsorship not stated One author employed by Schering AG
190
Participants
Interventions
Outcomes
Notes
Ruzicka 1998
(Continued)
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double-blind (patient/ assessor)
Unclear Yes Yes Yes
Salmhofer 2000 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 63 TD: 4 wks; FU: 8 wks LF: 5 (7.9%) BC: Yes Age: 47 (15.4SD, range: 19 to 83) Gender (%M): 54.0% Severity: Duration (months): 141 (124SD) PASI: 5.5 (2.65SD) INCLUSION CRITERIA Stable chronic plaque psoriasis; aged over 19; symmetrical lesions EXCLUSION CRITERIA Other types of psoriasis; BSA affected > 30%; concurrent systemic antipsoriatic therapy; pregnancy; lactation; concurrent infectious disease; other concurrent dematoses; hypercalcaemia; severe hepatic / renal disease
Participants
191
Salmhofer 2000
(Continued)
Interventions
Calcipotriol ointment, 5 mcg/g, BD (C) Calcipotriol ointment, 5 mcg/g, OM plus diucortolone valerate ointment, 0.1%, ON (D) PASI IAGI (7 pt: extreme deterioration to complete healing) PAGI (7 pt: extreme deterioration to complete healing) Sponsored by Schering Wien GmbH
Outcomes
Unclear Yes Yes Yes
not reported 7.9%
Sanchez 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Unclear WITHDRAWAL / DROPOUT Described N: 28 TD: 8 wks; FU: 8 wks LF: 3 (10.7%) BC: yes Age: 49.5 (range: 22 to 73) Gender (%M): 50% Severity: PASI: 7.7 (range: 4 to 10) INCLUSION CRITERIA
192
Participants
Sanchez 2001
(Continued)
Patients with plaque type psoriasis; EXCLUSION CRITERIA Systemic treatment within previous four wks; topical treatment within previous two wks; known hypersensitivity to sulphides; hypothyroidism; lactation Interventions Propylthiouracil cream, 5%, TD Calcipotriol ointment, 50 mcg/g, BD PASI Sponsorship not reported
Unclear Yes Yes Yes
not reported 10.7%
Santoianni 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: computer-generated list using block randomisation; pharmacy dispensed treatments in identical tubes Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 85 TD: 3 wks; FU: 3 wks LF: 4 (4.7%) BC: clinical only Age: 51.9 (range: 18.8 to 88.5)
193
Participants
Santoianni 2001
(Continued)
Gender (%M): 55.3% Severity: PASI: 6.2 INCLUSION CRITERIA Outpatients with disseminated keratotic plaque psoriasis; aged over 18 EXCLUSION CRITERIA Not reported Interventions Betamethasone 17-valerate 21 acetate plus tretinoine plus salicylic acid, OD Placebo, OD PASI IAGI (5 pt: worse to cured) PAGI (5 pt: no change to excellent): Adverse events Sponsored by IDI Farmaceuticia SpA
Outcomes
Yes Yes Yes Yes
partial
194
Scarpa 1994 Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Blinding unclear WITHDRAWAL / DROPOUT Not described N: 160 TD: 6 wks; FU: 10 wks LF: not reported BC: Demographics comparable, severity not reported Age: 50 Gender (%M): 68.1% Severity: not reported INCLUSION CRITERIA Plaque-type psoriasis EXCLUSION CRITERIA Not reported Calcipotriol ointment, 50 mg/g, BD (C) Betamethasone dipropionate ointment, 0.05% + salicylic acid, 3%, BD (B) Investigator global assessment (5 pt: null to excellent) Patients overall acceptance (5 pt: null to excellent) Sponsorship not reported
Participants
Interventions
Outcomes
195
Scarpa 1996 Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: block randomisation (6 patients) Concealment: unclear BLINDING Double-blind (patient /investigator) WITHDRAWAL / DROPOUT Described N: 76 TD: 6 wks; FU: 8 wks LF: 13 (17.1%) BC: Yes Age: not reported Gender (%M): not reported Severity: TSS: (0 to 12): 7.92 INCLUSION CRITERIA Chronic plaque psoriasis EXCLUSION CRITERIA Concomitant medications (except emollients, tar shampoo and salicylic acid); topical or systemic steroids; calcium or vitamin D intake; antipsoriatic medications Tacalcitol ointment, 4 mcg/g, OD (T) Betamethasone-17-valerate ointment 0.1%, OD (B) Severity [erythema; thickness; scaling] Total severity score (0 to 12) Comparison of lesions, based on difference in TSS Investigator global assessment (6-pt: worsening to healing) Patient assessment of difference Sponsorship not reported SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Authors judgement Unclear Yes Description B - Unclear double-blind (patient /investigator)
Yes Yes
block 17.1%
196
Scarpa 1996
(Continued)
Yes Yes
partial
Scarpa 1997 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: Not reported; tubes labelled left or right and with patient ID number Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 157 TD: 6 wks; FU: 7 wks LF: 23 (14.6%) BC: Yes Age: 49 (15SD; N = 134) Gender (%M):65.6% (N = 157) Severity: TSS (0 to 12): 7.7 INCLUSION CRITERIA Stable chronic plaque psoriasis; symmetrical lesions; in- and outpatients EXCLUSION CRITERIA Pregnancy; lactation; inadequate contraception; recent systemic, light or topical therapy; severe renal failure; liver and cardiac dysfunction; hypercalcemia; hyper phosphoremia; AIDS; drug addiction Tacalcitol ointment, 4 mcg/g, OD (T) Placebo (vehicle), OD (P) Signs: scaling; erythema; scaling TSS (0 to 12) Patient compliance (tube count; tube contents) Sponsorship: not reported, but Istituto Gentili SpA provided medications and appears to have undertaken the randomisation. SD imputation (TSS)
Participants
Interventions
Outcomes
Notes

197
Scarpa 1997
(Continued)
Unclear Yes
Unclear Yes Yes Yes
not reported 14.6%
Scher 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 31 patients TD: 24 wks; FU: 24 wks LF: not reported BC: Yes Age: 43 Gender (%M): 71% Severity: not reported INCLUSION CRITERIA Adults with psoriasis affecting at least two ngernails with at least three of the following characteristics: pitting, onycholysis, subungual hyperkeratosis, leukonychia, nail plate crumbling / loss, splinter haemorrhages, nail-bed discoloration EXCLUSION CRITERIA Duration of psoriasis < 6 mths; fungal infection of the nail; topical treatments for nails within previous 4 wks; intralesional corticosteroids or UV within previous 6 wks; systemic antipsoriatics within previous 12 wks Tazarotene gel, 0.1%, ON (T) Tazarotene gel, 0.1%, plus occlusion, ON (TO) Placebo gel, plus occlusion, ON (PO) Placebo gel, ON (P)
Participants
Interventions
198
Scher 2001
(Continued)
Outcomes
Pitting, onycholysis, nail plate crumbling / loss, splinter haemorrhages, nail-bed discoloration (7 pt scale) Adverse events Funded by an unrestricted educational grant from Allergen Skin Care, Irvine, CA Nail trial
Notes
not reported not reported partial
Sears 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 190 patients TD: 3 wks; FU: 3 wks LF: 21 (11%) BC: Yes Age: 44 (range: 19 to 73) Gender (%M): 47.9% Severity: Duration (yrs): 17 (range: 1 to 56) TSS (0 to 9): 6.0 INCLUSION CRITERIA
199
Participants
Sears 1997
(Continued)
Mild or moderate psoriasis not spontaneously remitting; adults aged 18 to 70; total sign score 3 to 8 EXCLUSION CRITERIA Acute systemic illness; hypothamic-pituitary-adrenal system disorder, severe hepatic or renal disorder; psoriatic infection; lactation, pregnancy or inadequate contraception; recent use of any corticosteroid, long-acting antihistamines, retinoids; drugs exacerbating or inuencing psoriasis; antimetabolic therapy; PUVA; ACE inhibitor; intolerant of topical corticosteroids or study medication Interventions Hydrocortisone buteprate 0.1% cream, BD (H) Placebo (vehicle) (P) Signs:[erythema; skin thickening; scaling] Total sign score (0 to 9) Pruritis Investigator and patient evaluations of efcacy (4 pt: poor to excellent) Investigator global assessment (7 pt: exacerbation to cleared) Compliance (actual vs. expected usage) Sponsorship: not reported
Outcomes
Notes Risk of bias Item Allocation concealment? Seidenari 1997 (H) Methods
DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 14 TD: 6 wks; FU: 8 wks LF: 3 (21.4%) BC: Yes Age: 46 (range 23 to 69, N = 26) Gender (%M): 46.2% (N = 26) Severity: TSS: 6.31 (1.25SD, N = 11) INCLUSION CRITERIA Symmetrical, stable psoriatic plaques; adult; in- or outpatients.
200
Participants
Seidenari 1997 (H)
(Continued)
EXCLUSION CRITERIA Recent topical, UV or systemic therapy. Inadequate contraception Interventions Tacalcitol ointment 4 mcg/g OD (T) Betamethasone valerate ointment 0.1%, OD (B) Signs: [erythema; thickening; scaling] Total sign score (0 to 12) Demographic characteristics summarised over both studies, placebo and active controls (N = 26)
Outcomes
Notes
Unclear Yes Yes Yes
not reported 21.4%
Seidenari 1997 (P) Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 12 TD: 6 wks; FU: 8 wks LF: 1 (8%) BC: Yes Age: 46 (range 23 to 69, N = 26)
201
Participants
Seidenari 1997 (P)
(Continued)
Gender (%M): 46.2% (N = 26) Severity: TSS: 6.50 (0.76SD, N = 11) INCLUSION CRITERIA Symmetrical, stable psoriatic plaques; adult; in- or outpatients. EXCLUSION CRITERIA Recent topical steroids, UV light, systemic or PUVA therapy. Inadequate contraception Interventions Tacalcitol ointment 4 mcg/g OD (T) Placebo (vehicle) (P) Signs: [erythema; thickening; scaling] Total sign score (0 to 12) Demographic characteristics summarised over both studies (N = 26) Sponsorship not reported
Outcomes
Notes
Unclear Yes Yes Yes
not reported 8.0%
Shuttleworth 1998 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: predetermined randomization schedule in blocks of ten Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
202
Shuttleworth 1998
(Continued)
Participants
N: 40 TD: 4 wks; FU: 4 wks LF: 3 (7.5%) BC: yes Age: 41.4 (12.0SD) Gender (%M):60.0% Severity: Investigators overall assessment (0 to 9): 4.85 Patients overall assessment (0 to 4): 2.43 INCLUSION CRITERIA Scalp psoriasis; aged 18 to 70 EXCLUSION CRITERIA Pregnancy; lactation; inadequate contraception; known hypersensitivity to study medication; participation in other study within previous month; concurrent systemic medication likely to affect psoriasis; photosensitivity; PUVA within previous two wks; helmet (diffuse) psoriasis; concurrent topical antipsoriatics; eye disease Ciclopirox olamine shampoo, 1.5%, 3 times / wk Placebo shampoo, 3 times / wk IAGI (7-pt: very much worse to completely cleared) Area affected Investigators overall assessment (extent of scalp psoriasis) (10 pt: normal to 75% scaling) Scaling (0 to 4.5) Pruritis Patient overall assessment (5 pt: poor to excellent) Adverse events Sponsored by Stiefel Laboratories Study was underpowered to detect a statistically signicant difference due to recruitment difculties Scalp trial
Interventions
Outcomes
Notes
Yes Yes Yes
block 7.5%
203
Shuttleworth 1998
(Continued)
Yes
Staberg 1998b Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 10 TD: 6 wks; FU: 6 wks LF: 1 (10%) BC: Yes Age: 50 (26 to 76) Gender (%M): not reported Severity: TSS (0 to 9): 7.3 INCLUSION CRITERIA Symmetrical chronic plaque psoriasis; inpatients; adult EXCLUSION CRITERIA None reported Calcipotriol cream, 1200 mcg/g BD (C) Placebo cream (P) Signs: [inltration; erythema; scaling] Total sign score (0 to 9) Sponsorship: Leo Pharmaceutical Products supplied the drugs and undertook the statistical analysis
Participants
Interventions
Outcomes
Notes
Unclear
not reported
204
Staberg 1998b
(Continued)
Yes Yes Yes
10.0% partial
Stein 2001 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: investigator undertook randomisation Concealment: inadequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 40 TD: 12 wks; FU: 12 wks LF: 3 (7.5%) BC: unclear Age: range: 20 to 70 + Gender (%M): not reported Severity: TSS (elbows) (0 to 12): 7.0 INCLUSION CRITERIA Mild to moderate symmetrical plaque, psoriasis; aged at least 18 EXCLUSION CRITERIA Systemic treatment within previous four wks; topical treatment within previous two wks; investigational medication within previous four wks Betamethasone valerate foam, 0.12% (Luxiq ), BD (B) Placebo foam, BD (P) IAGI (7 pt: worse to completely clear) Composite severity score (sum of change scores in erythema, scaling, thickness) (0 to 12) Pruritis BSA involvement Compliance (weight of containers) Sponsored by the Connetics Corporation SD imputation (IAGI)
Participants
Interventions
Outcomes
Notes

205
Stein 2001
(Continued)
No Unclear
C - Inadequate Double-blind (patient / investigator)
Stuecker 2001 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Blinding unclear WITHDRAWAL / DROPOUT Described N: 13 TD: 12 wks; FU: 12 wks LF: 2 (15.4%) BC: yes Age: 52.9 (12.2SD, range: 38 to 67) Gender (%M): 76.9% Severity: Duration: 20.8 (12.7SD) PASI: 9.11 (4.88SD, range: 2.20 to 18.70) INCLUSION CRITERIA Stable psoriasis vulgaris; aged 18 to 70 EXCLUSION CRITERIA Topical treatment within previous one wk; modication of systemic treatment within previous three mths; phototherapy within previous six wks; known hypersensitivity to study medications; avocado oil allergy; BSA 60% Calcipotriol cream, BD Vitamin B12 cream (with avocado oil), BD
Participants
Interventions
206
Stuecker 2001
(Continued)
Outcomes
PASI (modied to exclude head and neck; each side given weighting of 50%) IAGI (4 pt: poor to very good) PAGI (4 pt: poor to very good) Tolerability Sponsored by Regeneratio Pharma AG
Unclear Yes Yes Yes
not reported 15.4%
Stutz 1996 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation computer-generated randomisation code to allocate sides Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 15 TD: 3 wks; FU: 3 wks LF: 2 (13.3%) BC: Not reported Age: range: 21 to 68 Gender (%M): not reported Severity: TSS (scale not reported): 2.8 (0.3SD) INCLUSION CRITERIA Mild plaque psoriasis EXCLUSION CRITERIA
207
Participants
Stutz 1996
(Continued)
Prescription treatments within previous two wks Interventions Polymyxin B cream, 200,000U/g, TD Placebo cream, TD Total severity Erythema, scaling, thickness Sponsored by Babcock Dermatologic Endowment and by the alumni of the Department of Dermatology, University of Michigan Medical Center, MI
Outcomes
Notes
Yes Yes Yes Unclear
computer-generated 13.3% partial not reported
Sudilovsky 1981 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: identical tubes allocated by random numbers table Concealment: adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 78 (57% psoriasis) TD: 3 wks; FU: 3 wks LF: 0% BC: Inadequately reported Age: not reported Gender (%M): not reported
208
Participants
Sudilovsky 1981
(Continued)
Severity: not reported INCLUSION CRITERIA Bilateral lesions of similar severity and duration EXCLUSION CRITERIA Recent corticosteroid medication; history of poor response to corticosteroids; concomitant local or systemic therapy that could affect psoriasis Interventions Halcinonide cream 0.1% OD + vehicle cream BD (H) Placebo (vehicle) TDS (P) Comparative therapeutic response (3 pt: equal response to markedly superior response) Absolute therapeutic response (4 pt: poor (< 25% improvement) to excellent (75 to 100% improvement)) Investigator global assessment: reects comparative and absolute responses (methodology unclear) Sponsored by the Squibb Institute for Medical Research Part of a larger study involving patients with atopic dermatitis and trialling other dosages; aggregated demographics reported
Outcomes
Notes
Unclear Yes Unclear Unclear
not reported 0.0% not reported not reported
209
Sutton 2001 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 53 patients TD: 8 wks; FU: 12 wks LF: 5 (9.4%) BC: yes Age: range: 26 to 67 Gender (%M): 58.5% Severity: Duration (yrs): 2 to 50 INCLUSION CRITERIA Psoriasis; good general health EXCLUSION CRITERIA Women of childbearing potential; systemic retinoids within previous six mths; NSAIDs, cytostatic agents or folic acid-containing vitamin preparations within previous one mth; topical or UV treatments within previous two wks Methotrexate gel (Azone ), 1%, OD Placebo gel, OD IAGI (6 pt: worse to cleared) Total severity score (erythema, thickness, scaling, pruritis) (0 to 20) Adverse events Sponsored by Cato Research Ltd and Durham Pharmaceuticals LLC, NC Treated lesions <= 20% BSA
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / investigator)
Unclear Yes
not reported 9.4%
210
Sutton 2001
(Continued)
Yes Yes
partial
Syed 1996 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Not reported Concealment: Unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 60 TD: 4 wks; FU: 52 wks LF: 0 (0%) BC: Yes Age: 25.6 (range: 18 to 50) Gender (%M): 60.0% Severity: PASI: 9.3 (range: 4.8 to 16.7) Duration (yrs): 8.5 (range: 1 to 21) INCLUSION CRITERIA Mild-to-moderate chronic plaque-type psoriasis; EXCLUSION CRITERIA Pregnancy; lactation; cytotoxic drugs; beta-blockers; recent systemic medication, UV therapy; epilepsy Aloe vera extract 0.5% hydrophilic cream, TDS (5 days/wk) Placebo cream, TDS (5 days/wk) PASI Cure rate Signicant clearing Sponsorship not reported Concomitant water soluble emollients permitted SDs imputed (PASI)
Participants
Interventions
Outcomes
Notes
Risk of bias
211
Syed 1996
(Continued)
Unclear Yes Yes Yes
not reported 0.0%
Syed 2001b Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 60 patients TD: 4 wks; FU: 8 wks LF: 0 (0%) BC: yes Age: 29.3 (range: 18 to 70) Gender (%M): 61.7% Severity: Duration (yrs): 9.6 (range: 1 to 24) PASI: 9.8 (range: 5.3 to 17.5) INCLUSION CRITERIA Chronic, mild to moderate, plaque type psoriasis; outpatients; PASI > 4 or BSA > 20% EXCLUSION CRITERIA Topical or systemic corticosteroids or cytotoxic drugs or beta-blockers or phototherapy within previous three mths; pregnancy; lactation; alcoholic problems; concurrent renal, hepatic or haematological abnormalities Methotrexate gel (Azone ), 0.25%, BD (5 days/wk) Placebo gel, BD, (5 days/wk)
Participants
Interventions
212
Syed 2001b
(Continued)
Outcomes
PASI Plaques cleared Adverse events Compliance ( 40 topical applications during 4 wk period) Sponsorship not reported SD imputation (PASI)
Notes
Unclear Yes Yes Yes
not reported 0.0%
Tham 1994 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: computer generated random numbers Concealment: unclear BLINDING Single-blind (investigator) WITHDRAWAL / DROPOUT Described N: 30 TD: 6 wks; FU: 6 wks LF: 3 (10%) BC: Yes Age: 40 (range: 20 to 74) Gender (%M): 56.7% Ethnicity: Chinese (70.0%), Indian (16.7%), Malay (10.0%) and Sikh (3.3%) Severity: Duration (years): 9.7 (range: 2 to 20)
213
Participants
Tham 1994
(Continued)
PASI: 6.65 INCLUSION CRITERIA Stable symmetrical chronic plaque-type psoriasis; adult EXCLUSION CRITERIA Recent systemic or UV therapy; hypercalcaemia; high calcium or vitamin D intake; impaired renal or hepatic function; previous poor response to tar; concomitant medications Interventions Calcipotriol ointment 50 mcg/g, BD (C) White soft parafn, OM plus coal tar solution BP in aqueous cream 15% ON (T) PASI (modied to exclude head) Severity: [erythema; inltration; desquamation] Investigator global assessment (5-pt: worse to cleared) Patient global assessment (5-pt: worse to cleared) Sponsored by Leo Pharmaceutical Products
Outcomes
Description B - Unclear single-blind (investigator)
Yes Yes Yes Yes
214
Tosti 1998 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / assessor) WITHDRAWAL / DROPOUT Described N: 58 (29 pts with 129 ngernails; 44 pts with 270 toenails) TD: 12 wks; FU: 26 wks LF: 5 (8.6%) BC: Psoriasis comparable, demographics unclear Age: 51.8 (14.8SD) Gender (%M): 60.3% Severity: Duration (yrs): 7.7 Subungual hyperkeratosis (ngernails): 2.3 (0.1SEM) Subungual hyperkeratosis (toenails): 2.8 (0.1SEM) INCLUSION CRITERIA Nail bed psoriasis with severe subungual hyperkeratosis; adult EXCLUSION CRITERIA Onchymycosis; pregnancy; lactation; severe renal or hepatic insufciency; hypersensitivity to study medication; concomitant vitamin D, or antipsoriatic therapy Calcipotriol ointment 50 mcg/g, BD (C) Betamethasone dipropionate, 64 mg/g + salicylic acid, 0.03g/g, ointment, BD (B) Nail thickness (nail plate + hyperkeratotic nail bed, mm) Nail thickness, % reduction from baseline Patient assessment of acceptability (5-pt: 0 = nil; 4 = excellent) Part sponsorship from Prodotti Formenti SRL Nail trial
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Authors judgement Unclear Yes Description B - Unclear double-blind (patient / assessor)
Unclear
not reported
215
Tosti 1998
(Continued)
Yes Yes Yes
8.6%
partial
van de Kerkhof 1989 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: Adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 10 TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Yes Age: range: 28 to 72 Gender (%M): 70% Severity: TSS (0 to 9): 7.2 INCLUSION CRITERIA Patients with symmetrical chronic stable plaque psoriasis EXCLUSION CRITERIA Topical antipsoriatic therapy within previous 2 wks; systemic antipsoriatic therapy within previous 1 mth; BSA affected <= 15% Calcitriol solution 2 mcg/ml, BD (C) Placebo (vehicle) (P) Severity: [erythema; thickness; scaling] TSS (0 to 9) Sponsorship: not reported, but one of the authors worked for Hoffmann-La Roche, Switzerland Authors state that allocation was concealed to the investigator, but provide no justication Low dose SD imputation (TSS)
Participants
Interventions
Outcomes
Notes
Risk of bias
216
van de Kerkhof 1989
(Continued)
Unclear Yes Yes Yes
van de Kerkhof 1996a Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 122 TD: 8 wks; FU: 12 wks LF: 19 (15.6%) BC: Inadequately reported Age: 44.8 (13.69SD) Gender (%M): 62.3% Severity: Duration (mths): 233.5 (175.9SD) BSA: 5.6% INCLUSION CRITERIA Stable plaque psoriasis; not localised on the scalp; BSA: 5.6%; Score 2 for erythema and desquamation and Score sum > 5; Caucasian adults and adolescents EXCLUSION CRITERIA Increased serum calcium or serum phosphate level; recent systemic or topical antipsoriatic treatment; serious disease; known allergy to study medication; recent participation in another clinical trial; expected poor compliance; calcium supplements; drugs inuencing calcium metabolism; corticosteroids; barbiturates; phenytoin; NSAIDs; pregnancy
Participants
217
van de Kerkhof 1996a
(Continued)
Interventions
Tacalcitol 4 mcg/g OD (T) Placebo (vehicle) (P) Signs: [erythema; inltration; desquamation] Total sign score (0 to 12) Severity Preference assessment Area of test lesions Investigator global assessment (4 pt: poor to v. good) Patient global assessment (4 pt: poor to v. good) Assessment of benet Post-treatment relapse Sponsored by Hermal Kurt Herrmann Maximum treatment area: 10% BSA SD imputation (TSS)
Outcomes
Notes
not reported 15.6%
not reported
218
van de Kerkhof 2002a Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 88 patients TD: 4 wks; FU: 5 wks LF: 7 (8.0%) BC: Yes Age: not reported Gender (%M): not reported Severity: PASI: 16.9 (range: 4.3 to 48.0) INCLUSION CRITERIA Inpatients or outpatients; aged 18 or over; chronic plaque psoriasis; scalp involvement EXCLUSION CRITERIA Other forms of psoriasis; systemic antipsoriatic treatment within previous six wks; UV treatment within previous six wks; impaired renal or hepatic function; history of urolithiasis or hypercalciurea; arthritis; immobilisation; hypo- or hyperthyroidism; heavy exposure to sunlight; pregnancy; lactation; planning of pregnancy Calcipotriol ointment, 50 mcg/g (80 to 100 g/wk) and calcipotriol scalp solution, 50 mg/ ml (30 to 50 ml/wk) (C) Dithranol / tar regimen (D) PASI (scalp assessed separately) TSS (SCALP: erythema, thickness, scaling) (0 to 12) IAGI (6 pt: worse to clearance) PAGI (6 pt: worse to clearance) Adverse events Sponsored by Leo Pharmaceutical Products Includes inpatients Reports medication quantities used: patients complied well High dose calcipotriol IAGI/PAGI: combined scalp/body TSS: scalp only PASI: body only
Participants
Interventions
Outcomes
Notes
219
van de Kerkhof 2002a
(Continued)
Unclear No
B - Unclear open
Unclear Yes Yes Yes
van der Vleuten 1995 Methods DESIGN Within patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Described N: 10 TD: 2 wks; FU: 2 wks LF: 0 (0%) BC: Inadequately reported Age: range: 20 to 72 Gender (%M): 40% Severity: Duration (yrs): 3 to 53 PASI (modied): 17.1 (2.1SEM) INCLUSION CRITERIA Adult; inpatient; severe, disabling psoriasis; resistant to topical therapy EXCLUSION CRITERIA Recent or concomitant oral antipsoriatic therapy, no topical or systemic treatments except corticosteroids for the scalp and face Calcipotriol ointment, 50 mcg/g, BD Dithranol in paste or petroleum, 0.05% to 4%, 24 hour application on alternate days PASI (excludes scalp)
Participants
Interventions
Outcomes
220
van der Vleuten 1995
(Continued)
Notes
Sponsorship not reported Inpatients
Vanderploeg 1976 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: identical tubes allocated by sequential admission number, corresponding to a standard randomization schedule using a double-blind code Concealment: adequate BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 36 TD: 3 wks; FU: 3 wks LF: 3 of 36 (8.3%) BC: Yes Age: 45.7 (range: 10 to 66; N = 33) Gender (%M): 48.5% (N = 33) Severity: TSS (0 to 20): 9.9 INCLUSION CRITERIA Psoriasis or atopic dermatitis EXCLUSION CRITERIA Recent systemic or topical steroids; concomitant medications
Participants
221
Vanderploeg 1976
(Continued)
Interventions
Betamethasone dipropionate ointment, 0.05%, BD (B) Vehicle, BD (P) Signs: [scale; erythema; pruritis; thickness; crusting] Total sign score (0 to 20) Investigator global assessment (5 pt: exacerbation to excellent improvement) Sponsorship: not reported Part of a larger trial that included patients with atopic dermatitis (50% psoriasis) SD imputation (TSS)
Outcomes
Notes
Yes Yes Yes Yes
sequential 8.3%
Veien 1997 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: block Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 287 TD: 8 wks FU: 12 wks LF: 0 (0%) BC: Psoriasis comparable, demographics inadequately reported Age: 45.0 Gender (%M): 53.7%
222
Participants
Veien 1997
(Continued)
Severity: BSA: 7.9% (range: 1 to 75%) TSS (0 to 12): 7.59 INCLUSION CRITERIA Adult; stable plaque psoriasis; TSS > 5; erythema 2, scaling 2 EXCLUSION CRITERIA Pregnancy; lactation; high serum calcium, serum phosphate, serum creatinine; unresponsive to calcipotriol; intolerant to study ingredients; serious co-morbidity Interventions Tacalcitol ointment, 4mcg/g, OD plus Tacalcitol vehicle OD (T) Calcipotriol ointment, 50 mcg/g, BD (C) Severity: [erythema; inltration; scaling; pruritus] Total sign score (TSS): (0 to12) Investigator global assessment (6-pt: worse to clear) Patient global assessment (scale virtually identical to IAGI; details not reported) Patient evaluation of global usefulness (VAS) Patient evaluation of cosmetic acceptability Quantity of medication used Rebound (aggravation equal to or worse than pre-treatment severity) Sponsored by Nycomed Pharma
Outcomes
Yes Yes Yes Unclear
block 0.0%
not reported
223
Vladimirov 1994 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Not described N: 60 TD: 6 wks; FU: 6 wks LF: 0 (0%) BC: Inadequately reported Age: range: 18 to 70 Gender (%M): not reported Severity: Duration (yrs): range: 0.2 to 30 PASI: 2.92 INCLUSION CRITERIA Adult; mild to moderate psoriasis EXCLUSION CRITERIA None reported Calcipotriol cream50 mcg/g, BD (C) Betamethasone17-valerate ointment 0.1%, BD (B) PASI (range unclear) Investigator global assessment (scale NR) Sponsored by Leo Pharmaceuticals SD imputation (PASI)
Participants
Interventions
Outcomes
Notes
Unclear Yes Yes

224
Vladimirov 1994
(Continued)
Unclear
not reported
Volden 1992 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 10 TD: 4 wks; FU: 4 wks LF: 1 (10%) BC: Yes Age: not reported Gender (%M): not reported Severity: Duration (mean years): 20 BSA: 5 to 15% INCLUSION CRITERIA Symmetrical plaque-type psoriasis; adult outpatients EXCLUSION CRITERIA Recent active treatment for psoriasis Dithranol 1% in petrolatum (D) Placebo (vehicle) (P) Signs: [erythema; inltration; scaling] Total sign score (0 to 12) Sponsorship not reported but one of the authors worked for Hydro Pharma, Sweden
Participants
Interventions
Outcomes
Notes Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported?
Description B - Unclear double blind (patient / investigator)
Unclear
not reported
225
Volden 1992
(Continued)
Yes Yes Yes
10.0% partial
Wall 1998 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Open WITHDRAWAL / DROPOUT Not described N: 306 TD: 3 mths LF: 28 (7.2%) BC: Yes Age: 46.7 Gender (%M): 47.1% Severity: Duration (yrs): 18.7 Signs and extent reported, but not by summary measure INCLUSION CRITERIA Adult; stable mild-to-moderate chronic plaque psoriasis; BSA 100cm but < 40%; recent GP visit EXCLUSION CRITERIA Acute guttate or pustular psoriasis; psoriasis of scalp or face only; recent topical or systemic antipsoriatic therapy; pregnancy; lactation; concomitant vitamin D or calcium intake; hypersensitivity to study medication; unlikely to comply with protocol Calcipotriol ointment, 50 mcg/g, BD (C) Dithranol 0.1 to 2%, OD (D) Investigator assessment of overall clinical response (5 pt: worse to clear) Patient assessment of overall clinical response (5 pt: worse to clear) Quality of Life: Psoriasis Disability Index (PDI) Sickness Impact Prole (SIP) Sponsored by Leo Pharmaceuticals
Participants
Interventions
Outcomes
Notes
226
Wall 1998
(Continued)
Unclear Yes Yes Yes
Weinstein 1996 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 324 TD: 12 wks; FU: 24 wks LF: 6 (1.9%) BC: Yes Age: 46.8 (range: 12 to 83) Gender (%M): 67% Severity: % BSA: 6.9 (5.2SD) Duration (yrs): 17.5 (12.7SD) TSS (0 to 12): 7.3 INCLUSION CRITERIA Stable plaque psoriasis; BSA 20%; 2 target lesions with plaque elevation 2 and 2cm in diameter; 1 on elbow/knee and 1 on trunk/limbs. EXCLUSION CRITERIA Pustular or exfoliative psoriasis; sensitivity to study medication; other confounding skin conditions; recent use of tar shampoos; topical/ systemic/light therapies; topical corticosteroids/ UVB; PUVA / systemic therapy; oral retinoids; uncontrolled systemic disease; pregnant;
227
Participants
Weinstein 1996
(Continued)
lactating; inadequate contraception Interventions Tazarotene gel, 0.1% OD Tazarotene gel, 0.05% OD Placebo (vehicle) (P) Signs: [plaque elevation; scaling; erythema] Total Sign Score (0 to 12) % clearance Patient assessment of cosmetic acceptability Sponsored by Allergan Inc. Authors state that concealment of treatment allocation achieved for patients and clinicians, as tubes were identical SD imputation (TSS)
Outcomes
Notes
Unclear Yes Yes Yes
not reported 1.9%
Weinstein 2003 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: Randomised in blocks of 6 Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described
228
Weinstein 2003
(Continued)
Participants
N: 1303 TD: 12 wks; FU: 24 wks LF: 411 (31.5%) BC: Yes Age: 48.2 (range: 18 to 84) Gender (%M): 62.6% Severity: OLA (0 to 5)(mean): 3.6 Duration (mean yrs): 18.4 BSA affected (mean): 10.5% INCLUSION CRITERIA Aged 18; BSA 2%; OLA (0 to 5) 3; acceptable blood or urinary test results EXCLUSION CRITERIA Pregnancy or risk thereof; lactation; UV or topical therapies within previous two wks; PUVA or systemic therapies within previous four wks; oral retinoid therapy within previous eight wks; expected prolonged exposure to UV light Tazarotene cream 0.05%, OD (T1) Tazarotene cream 0.1%, OD (T2) Placebo (P) Overall lesion assessment (OLA; 0 = none to 5 = very severe), as applied to all treated lesions Clinical success (OLA 2 at 12 wks) Effectiveness (improvement in OLA from baseline of 15% relative to placebo improvement score) Overall plaque elevation, scaling and erythema (each scored 0 = none to 4 = severe) Overall global response to treatment (7 pt: completely cleared to worsened) Target lesion response (7 pt: completely cleared to worsened) Sponsored by Allergan Inc. Reports two trials, only study A reported follow up data after 12 weeks (N = 108)
Interventions
Outcomes
Notes
Yes Yes Yes Yes
block 31.5%
229
Wolska 1995 Methods DESIGN Within patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (patient / investigator) WITHDRAWAL / DROPOUT Described N: 52 TD: 4 wks; FU: 4 wks LF: 12 (23.1%) BC: yes Age: 44.7 (range: 18 to 77; N = 40) Gender (%M): 70%; N = 40 Severity: TSS (0 to 9) (median): 7.1 (range: 6.0 to 9.0) INCLUSION CRITERIA Plaque type psoriasis; at least 2 symmetrical lesions, excluding those on neck, head, feet and hands; TSS 6; between-plaque TSS scores 1; lesions clinically stable 1wk EXCLUSION CRITERIA Topical antipsoriatic treatment (tar / dithranol / steroids) within previous two wks; systemic antipsoriatic treatment (steroids / retinoids / methotrexate / cyclosporin) within previous four wks; UV treatment within previous four wks; pregnancy; lactation; inadequate contraception; impaired renal or hepatic function Platelet aggregation activating factor (PAF) (Ro 24 to 0238) , 10% solution, BD Placebo solution, BD TSS (erythema, desquamation, inltration) (0 to 9) IAGI (6 pt: marked worsening to total clearing) Adverse events Sponsorship not reported Inpatients
Participants
Interventions
Outcomes
Notes
Unclear
not reported
230
Wolska 1995
(Continued)
Yes Yes Yes
23.1%
Wortzel 1975 (1) Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: sequential admission number Concealment: adequate BLINDING Double-blind (patient / physician) WITHDRAWAL / DROPOUT Not described N: 76 TD: 3 wks; FU: 3 wks LF: 0 (0%) BC: not reported Age: not reported Gender (%M): not reported Severity: not reported INCLUSION CRITERIA Moderately severe to very severe psoriasis and atopic dermatitis; Outpatients EXCLUSION CRITERIA Not reported Betamethasone dipropionate ointment 0.05, BD (B) Placebo, BD (P) IAGI (5pt: worse to excellent) Physician opinion of drug effect (scale unclear, results not reported) Sponsored by Leo Pharmaceuticals
Participants
Interventions
Outcomes
Description A - Adequate double-blind (patient / physician)

231
Wortzel 1975 (1)
(Continued)
Randomisation method reported? Loss to follow up? Baseline comparability demonstrated?
Yes Yes Unclear
sequential 0.0% not reported
Wortzel 1975 (2) Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: sequential admission number Concealment: adequate BLINDING Double-blind (patient / physician) WITHDRAWAL / DROPOUT Not described N: 9 TD: 3 wks; FU: 3 wks LF: 0 (0%) BC: not reported Age: not reported Gender (%M): not reported Severity: not reported INCLUSION CRITERIA Moderately severe to very severe psoriasis and atopic dermatitis; Inpatients EXCLUSION CRITERIA Not reported Betamethasone dipropionate ointment 0.05, BD (B) Placebo, BD (P) IAGI (5pt: worse to excellent) Physician opinion of drug effect (scale unclear, results not reported) Sponsorship not reported Concomitant water soluble emollients permitted SD imputation (PASI)
Participants
Interventions
Outcomes
Notes
Risk of bias Item Allocation concealment? Authors judgement Yes Description A - Adequate
232
Wortzel 1975 (2)
(Continued)
Yes
double-blind (patient / physician)
Yes Yes Unclear Unclear
sequential 0.0% not reported not reported
Wozel 2001 Methods DESIGN Between patient Patient delivery ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (unclear) WITHDRAWAL / DROPOUT Described N: 38 TD: 2 wks; FU: 6 wks LF: 0 (0%) BC: Yes (statistical signicance not reported) Age: not reported Gender (%M): not reported Severity: not reported INCLUSION CRITERIA Chronic plaque psoriasis EXCLUSION CRITERIA Not reported Calcipotriol ointment OM plus uocinolone acetonide ointment, 0.025% ON (CF) Calcipotriol ointment OM plus vehicle ointment, ON (CP) four weeks maintenance for both groups with calcipotriol ointment BD PASI Sponsorship not reported
Participants
Interventions
Outcomes Notes Risk of bias
233
Wozel 2001
(Continued)
Description B - Unclear double-blind (unclear who was blinded)
not reported 0.0% not reported
Zonneveld 1998 (H) Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (but unmatched regimens) (patient / assessor) WITHDRAWAL / DROPOUT Not described N: 70 TD: 6 wks; FU: 6 wks LF: Not reported BC: Yes (clinical); demographics not reported Age: not reported Gender (%M): not reported Severity: median LPSI ranged from 7.0 (C;T) to 8.0 (P) INCLUSION CRITERIA Chronic plaque psoriasis. LPSI 6 EXCLUSION CRITERIA Not reported Calcipotriol ointment, 0.005%, BD (C) Tacrolimus ointment, 0.3%, OD (T) Placebo ointment, BD (P) Local psoriasis severity index (scale NR)
Participants
Interventions
Outcomes
234
Zonneveld 1998 (H)
(Continued)
Notes
Double blind (but unmatched regimens) Sponsored by Fujisawa GmbH SD imputation (TSS)
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double-blind (but unmatched regimens) (patient / assessor) not reported not reported partial partial
Zonneveld 1998 (P) Methods DESIGN Between patient Delivery unclear ALLOCATION Random Method of randomisation: not reported Concealment: unclear BLINDING Double-blind (but unmatched regimens) (patient / assessor) WITHDRAWAL / DROPOUT Not described N: 70 TD: 6 wks; FU: 6 wks LF: Not reported BC: Yes (clinical); demographics not reported Age: not reported Gender (%M): not reported Severity: median LPSI ranged from 7.0 (C;T) to 8.0 (P) INCLUSION CRITERIA Chronic plaque psoriasis. LPSI 6 EXCLUSION CRITERIA Not reported
Participants
235
Zonneveld 1998 (P)
(Continued)
Interventions
Calcipotriol ointment, 0.005%, BD (C) Tacrolimus ointment, 0.3%, OD (T) Placebo ointment, BD (P) Local psoriasis severity index (scale NR) Double blind (but unmatched regimens) Sponsored by Fujisawa GmbH SD imputation (TSS)
Outcomes Notes
Risk of bias Item Allocation concealment? Blinding? All outcomes Randomisation method reported? Loss to follow up? Baseline assessments? Baseline comparability demonstrated? Authors judgement Unclear Yes Description B - Unclear double-blind (but unmatched regimens) (patient / assessor) not reported not reported
partial
Characteristics of excluded studies [ordered by study ID]
Study Ambroziak 2002 Baadsgaard 1995
Reason for exclusion Compares steroid against no treatment (rather than against placebo) Study is within-patient but does not adopt clear left-right design and assesses multiple plaques for each participant No adequate data reported or available from triallists Compares steroid against no treatment (rather than against placebo) No adequate data reported or available from triallists or sponsor Comparator is not strictly placebo (salicylic acid in vehicle)
Baran 1999 Bianchi 2003 Callen 1996 Carroll 2005
236
(Continued)
De Jong 1999 Elias 1994 Jansen 1986 Kragballe 1989
Comparator is not strictly placebo (urea in vehicle) Unclear if valid randomised controlled trial No adequate data reported Patients were randomised to the two substudies but within the substudies treatments were applied without randomisation Dose ranging study of an unlicensed product not subsequently marketed The study does not provide a simple comparison against a vitamin D3 derivative treatment No adequate data reported or available from triallists or sponsor No adequate data reported or available from triallists or sponsor The study does not provide a comparison of interest No adequate data reported or available from triallists or sponsor No adequate data reported or available from triallists or sponsor The study does not provide a simple comparison against a vitamin D3 derivative treatment No adequate data reported or available from triallists or sponsor Study uses concomitant UV light No adequate data reported or available from triallists No translation available Study uses concomitant UV light No adequate data reported or available from triallists
Kragballe 1994 Lebwohl 1998b Lebwohl 2001 Levin 2003 Meyrat 1996 Reygagne 2002a Ruzicka 2004 Sander 1998 Sefton 1984 Sharma 2003 Syed 2001a Tokura 2004 Tzaneva 2003 van de Kerkhof 1996b
Characteristics of studies awaiting assessment [ordered by study ID]
237
Bernstein 2006 Methods Participants Interventions Outcomes Notes Beutner 2006 Methods Participants Interventions Outcomes Notes Beutner 2006a Methods Participants Interventions Outcomes Notes Brown 2005 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
238
Buckley 2008 Methods Participants Interventions Outcomes Notes de Korte 2008 Methods Participants Interventions Outcomes Notes Friedrich 2004 Methods Participants Interventions Outcomes Notes Gold 2006 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
239
Gottschalk 2007 Methods Participants Interventions Outcomes Notes Helfrich 2007 Methods Participants Interventions Outcomes Notes Jarratt 2006 Methods Participants Interventions Outcomes Notes Jemec 2007 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
240
Jemec 2008 Methods Participants Interventions Outcomes Notes Ji 2008 Methods Participants Interventions Outcomes Notes Jorizzo 2007 Methods Participants Interventions Outcomes Notes Kaur 2004 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
241
Koo 2006 Methods Participants Interventions Outcomes Notes Kragballe 2006 Methods Participants Interventions Outcomes Notes Kragballe 2006a Methods Participants Interventions Outcomes Notes Kragballe 2006b Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
242
Kreuter 2006 Methods Participants Interventions Outcomes Notes Lebwohl 2007 Methods Participants Interventions Outcomes Notes Lee 2007 Methods Participants Interventions Outcomes Notes Liao 2007 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
243
Lowe 2005 Methods Participants Interventions Outcomes Notes Luger 2008 Methods Participants Interventions Outcomes Notes Luger 2008a Methods Participants Interventions Outcomes Notes Maier 2004 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
244
Menter 2008 Methods Participants Interventions Outcomes Notes Ortonne 2006 Methods Participants Interventions Outcomes Notes Powers 2005 Methods Participants Interventions Outcomes Notes Powers 2005a Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
245
Reygagne 2005 Methods Participants Interventions Outcomes Notes Saraceno 2007 Methods Participants Interventions Outcomes Notes Saraswat 2007 Methods Participants Interventions Outcomes Notes van de Kerkhof 2005 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
246
van de Kerkhof 2006 Methods Participants Interventions Outcomes Notes van de Kerkhof 2007 Methods Participants Interventions Outcomes Notes White 2006 Methods Participants Interventions Outcomes Notes Xuejun 2005 Methods Participants Interventions Outcomes Notes Not yet assessed Not yet assessed Not yet assessed Not yet assessed
247
Zhu 2007 Methods Participants Interventions Outcomes Notes Not yet assessed
Characteristics of ongoing studies [ordered by study ID]

Altmeyer Trial name or title Methods Participants Interventions Topical Vitamin B12 in Chronic Plaque Psoriasis Multicentre double-blind randomised placebo-controlled trial Volunteer sample of 51 participants with chronic plaque psoriasis. Minimum age: 18 All participants applied vitamin B12 cream twice daily for 8 weeks to one side of the body and placebo to the other Modied Psoriasis Area and Severity Index (PASI) at weeks 0, 2, 4, 6 and 8. Thickness and density of 3 references plaques determined by 20 MHz sonography. Assessment of efciency and tolerability by participants and investigators January 2001 Peter Altmeyer, Prof. Dr., Principal Investigator, Ruhr University Bochum, Dep. Dermatology and Allergology
Outcomes
Starting date Contact information Notes Angulo Trial name or title Methods
Study to Compare U0267 Foam Against Vehicle Foam in Subjects With Plaque-Type Psoriasis Treatment, Randomized, Double-blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Male or female subjects at least 12 years old and in good general health. - Mild to moderate plaque-type psoriasis Exclusion Criteria: - Known allergy or other adverse reaction to calcipotriene or other vitamin D analogs; or to any component of the investigational formulations - History of hypercalcemia or of vitaminD toxicity.
248
Participants
Angulo
(Continued)
- Diagnosis of generalized pustular or erythrodermic exfoliative psoriasis. - Other serious skin disorder or any chronic medical condition that is not well controlled. - Use of non-biologic systemic anti-psoriatic therapy or biologic therapy within four weeks of enrollment. - Use of topical therapies that have a known benecial effect on psoriasis, within two weeks of enrollment. - Systemic medications for other medical conditions that are known to affect psoriasis within the past four weeks of enrollment. - Use of any investigational therapy within four weeks of enrollment. - Pregnant women, women who are breast feeding, or sexually active women of child bearing potential who are not practicing an acceptable method of birth control Interventions Drug: U0267 Foam Drug: Vehicle Foam An ISGA score of clear (0) or almost clear (1), and A minimum improvement in the ISGA score of 2 grades from baseline to week 8 A target lesion score of 0 or 1 for erythema and at least a 2 grade improvement from baseline; a target lesion score of 0 or 1 for scaling and at least a 2 grade improvement from baseline; a target lesion score of 0 for plaque thickness 8 weeks April 2008 David A. Angulo, MD, Study Director, Stiefel Labortories, Inc
Outcomes
Starting date Contact information Notes Bibby Trial name or title Methods Participants
Efcacy and safety of calcipotriene / Betamethasone Gel / Ointment in Psoriasis Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efcacy Study Psoriasis involving at least 10% of the scalp and amenable to topical treatment with a maximum of 40 g of gel per week. - A score for the investigators assessment of clinical signs of scalp psoriasis of at least two (moderate severity) in one of the clinical signs (redness, thickness and scaliness), and at least one (slight severity) in each of the other two clinical signs. - An investigators global assessment of moderate, severe or very severe scalp psoriasis. - Psoriasis vulgaris of the trunk and/or limbs amenable to topical treatment with a maximum of 60 g of ointment per week. - An investigators global assessment of moderate, severe or very severe psoriasis of trunk/limbs. - Attending a hospital out-patient clinic or the private practice of a dermatologist for treatment of psoriasis. - Participants who self-report: - their ethnicity as Hispanic or Latino, and who are of any race, - their ethnicity as not Hispanic or Latino, and their race as Black or African American. - Following receipt of verbal and written information about the trial, the participant must provide signed and dated informed consent before any trial-related activity is carried out. - Females of child-bearing potential must have a negative result for a urine pregnancy test before randomisation and must agree to use an adequate method of contraception during the study.
249
Bibby
(Continued)
- Participants fullling US requirements/law for participation in this study. Exclusion Criteria: - PUVA or Grenz ray therapy within four weeks prior to randomisation. - UVB therapy within two weeks prior to randomisation. - Systemic treatment with biological therapies (marketed or otherwise) with a possible effect on psoriasis (e. g., alefacept, efalizumab, etanercept, iniximab) within three months prior to randomisation. - Systemic treatment other than biologicals with a possible effect on psoriasis (e.g., corticosteroids, vitamin D analogues, retinoids, hydroxycarbamide, azathioprine, methotrexate, cyclosporine, other immunosuppressants) within four weeks prior to randomisation. - Any topical treatment of the scalp (except for medicated shampoos and emollients) within two weeks prior to randomisation (medicated shampoos/emollients are not allowed during the double-blind phase). Shampoos containing corticosteroids, e.g. Clobex , are not allowed within two weeks prior to randomisation. - Planned use of topical treatment for psoriasis of the trunk or limbs, besides study medication, during the study with the exceptions of: emollient medications used to treat psoriasis of the skin folds and/or genitals (any medication may be used for this purpose apart from Class 1 to 5 corticosteroids. - Topical treatment of the face with Class 1 to 5 corticosteroids within 2 weeks prior to randomisation. - Planned initiation of, or changes to, concomitant medication that could affect psoriasis (e.g., beta blockers, anti-malaria drugs, lithium) during the double-blind phase of the study. - Treatment with any non-marketed drug substance (i.e., an agent which has not yet been made available for clinical use following registration) within four weeks prior to randomisation. - Planned use of chemical treatments of the hair (e.g. relaxers, perms, or colourings) during the double-blind phase of the study. - Current diagnosis of erythrodermic, exfoliative or pustular psoriasis. - Participants with any of the following conditions also present on psoriatic areas of the scalp or trunk/limbs: viral (e.g. herpes or varicella) lesions of the skin, fungal or bacterial skin infections, parasitic infections, skin manifestations in relation to tuberculosis or syphilis, rosacea, acne rosacea, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, ulcers or wounds. - Other inammatory skin diseases that may confound the evaluation of psoriasis of the scalp or trunk/limbs Interventions Calcipotriene Plus Betamethasone Dipropionate Gel Compared to the Gel Vehicle in Scalp Psoriasis, in participants Receiving Calcipotriene Plus Betamethasone Dipropionate Ointment for Psoriasis Vulgaris of Trunk/Limbs To compare the efcacy (in terms of participants with clear or minimal disease) of eight weeks treatment with combination (calcipotriene plus betamethasone dipropionate) gel with that of the gel vehicle in scalp psoriasis Octrober 2006 S Tyring, MD, Principal Investigator, Center for Clinical Studi
Outcomes
Starting date Contact information Notes
250
Cytochroma Trial name or title Methods Participants Safety and Efcacy of Topically Applied CTA018 in Plaque Psoriasis Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - clinical diagnosis of chronic plaque psoriasis for 6 months to a max 15% body surface area excluding face, scalp, groin, axillae, palms, soles of feet - at least 2 evaluable plaques with CPSS >/= 6 - baseline PSGA >/= 2 - women of childbearing potential must agree to use an effective form of contraception Exclusion Criteria: - cannot have guttate, pustular, erythrodermic or other non-plaque forms of psoriasis - cannot have concomitant serious illness/condition that may interfere with participation in the study - cannot have used topical therapy within two weeks prior to baseline visit - cannot have used photo-therapy or systemic psoriasis therapy within four weeks prior to baseline visit - cannot have had prolonged exposure to natural or articial UV radiation within four weeks of baseline visit or intend to have exposure during the study - cannot have used systemic immunomodulatory therapy within 12 weeks prior to baseline visit - cannot have a history of hypercalcemia or kidney stones - cannot be unable or unwilling to discontinue calcium and/or vitamin D supplementation during the study - cannot be pregnant or a nursing mother - cannot be participating in or have participated in an interventional study within 30 days of study start Drug: CTA018 cream The primary endpoint will be treatment success or failure based on a Physicians Static Global Assessment (PSGA) of 0 or 1 (success) September 2006 Not supplied
Starting date Contact information Notes Fleming 2006 Trial name or title Methods Participants
Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel in Psoriasis Vulgaris Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Psoriasis vulgaris involving trunk and/or arms and/or legs amenable to treatment with a maximum of 100 g of topical medication per week - An investigators global assessment of disease severity of at least mild Exclusion Criteria: - PUVA or Grenz ray therapy within four weeks prior to randomisation - UVB therapy within two weeks prior to randomisation - Systemic treatment with biological therapies, with a possible effect on psoriasis vulgaris within six months
251
Fleming 2006
(Continued)
prior to randomisation - Systemic treatment with all other therapies than biologicals, with a possible effect on psoriasis vulgaris (e.g. , corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within four weeks prior to randomisation - Any topical treatment of the trunk/limbs (except for emollients) within two weeks prior to randomisation - Topical treatment for other relevant skin disorders (except WHO group I-II corticosteroids, tar, retinoid and dithranol on face, scalp, or exures) within two weeks prior to randomisation - Planned initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, anti-malaria drugs, lithium) during the study - Current diagnosis of guttate, erythrodermic, exfoliative or pustular psoriasis Interventions Outcomes Drug: Calcipotriol plus betamethasone dipropionate (LEO 80185) gel Participants with controlled disease (minimal or clear and at least two steps change from baseline) according to the investigators global assessment of disease severity at week four and week eight The absolute and percentage change in PASI from baseline to week 1, 2, 4, 6, and 8. Participants with controlled disease according to the investigators global assessment of disease severity at week 1, 2, and 6. Participants with clear or very mild disease by the participants global assessment of disease severity at week 1, 2, 4, 6, and 8 December 2005 Colin Fleming, MD, Principal Investigator, Ninewells Hospital and Medical School, Ninewells, Dundee, UK
Starting date Contact information Notes Fleming 2008 Trial name or title
Efcacy and Safety of Calcipotriol Plus Hydrocortisone Ointment Compared With Tacalcitol Ointment in Patients With Psoriasis on the Face and Skin Folds Treatment, Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Clinical diagnosis of psoriasis vulgaris involving the face - Clinical signs of psoriasis vulgaris on the trunk and/or the limbs, or earlier diagnosed with psoriasis vulgaris on the trunk and/or the limbs - An extent of psoriatic involvement of the face of at least 10 cm2 (the sum of all facial lesions) - Treatment areas (the face and the intertriginous areas) amenable to topical treatment with a maximum of 10 g of ointment per day - Disease severity graded as mild, moderate, severe or very severe according to the investigators global assessment of disease severity of the face Exclusion Criteria: - Systemic treatments with all other therapies than biologicals, with a potential effect on psoriasis vulgaris (e. g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within the four week period prior to randomisation
252
Methods
Participants
Fleming 2008
(Continued)
- Systemic use of biological treatments, whether marketed or not, directed against or with a potential effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, iniximab, adalimumab) within three months prior to randomisation - PUVA therapy or Grenz ray therapy within the four week period prior to randomisation - UVB therapy within the two week period prior to randomisation - Topical treatment of the face and the intertriginous areas within the two week period prior to randomisation (use of emollients is allowed on treatment areas during this two week period, but not during the study) - Topical treatment with very potent WHO group IV corticosteroids within the two week period prior to randomisation - Initiation of or expected changes in concomitant medication that may affect psoriasis vulgaris (e.g., beta blockers, anti-malaria drugs, lithium and ACE inhibitors) during the study - Systemic treatment with vitamin D preparations above 500 IU per day - Current diagnosis of erythrodermic, exfoliative, guttate or pustular psoriasis - Participants with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions of the skin, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds - Other inammatory skin diseases(e.g., seborrhoeic dermatitis, contact dermatitis and cutaneous mycosis) that may confound the evaluation of psoriasis vulgaris on the face or on the intertriginous areas - Planned exposure to sun, UVA or UVB that may affect the psoriasis vulgaris during the study - Known or suspected severe renal insufciency or severe hepatic disorders - Known or suspected disorders of calcium metabolism associated with hypercalcemia Interventions Outcomes Starting date Contact information Drug: Calcipotriol and hydrocortisone (LEO 80190) Overall disease severity of the face according to the investigators assessment Week eight February 2008 Colin Fleming, MD, Principal Investigator, Ninewells Hospital & Medical School Kirsten L Noerrelund, MSc Pharm tel: +4544945888 kirsten.noerrelund@leo-pharma.com
Notes Gottschalk Trial name or title Methods Efcacy, Safety, Preference and Response Duration of Clobex Spray and Taclonex Ointment in Psoriasis Treatment, Randomized, Single-Blind (Outcomes Assessor), Active Control, Parallel Assignment, Efcacy Study Inclusion Criteria: - Moderate to severe psoriasis involving 3 to 20% of the body surface area Exclusion Criteria: - Subjects who have surface area involvement too large that would require more than 50 grams per week of Clobex Spray or more than 100 grams per week of Taclonex Ointment
253
Participants
Gottschalk
(Continued)
- Subjects having psoriasis that involves the scalp, face, or groin Interventions Drug: Clobetasol Propionate, 0.05% Drug: Calcipotriene and betamethasone dipropionate ointment Overall Disease Severity End of treatment (Week 4) No Tolerability assessments, incidence of adverse events Baseline, Weeks 1, 2, 4 and 8 Yes August 2006 Ronald W Gottschalk, MD, Study Director, Galderma Laboratories, LP
Outcomes
Starting date Contact information Notes Hoffmann Trial name or title
Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel Compared With Tacalcitol Ointment and the Gel Vehicle Alone in Patients With Psoriasis Vulgaris Treatment, Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Signed and dated informed consent to be obtained prior to any trial related procedure, including wash-out - Clinical diagnosis of psoriasis vulgaris involving trunk and/or arms and/or legs amenable to treatment with a maximum of 100 g of LEO 80185 gel per week or 10 g per day of tacalcitol ointment - Disease severity graded moderate, severe or very severe according to the Investigators global assessment (IGA) of disease severity - A minimum PASI score for extent of 2 in at least one body region (i.e. psoriasis affecting at least 10% of arms, and/or 10% of trunk, and/or 10% of legs) - Subjects aged 18 years or above - Either sex - Any ethnic origin - Attending hospital outpatient clinic or the private practice of a dermatologist Exclusion Criteria: - Systemic treatment with biological therapies (marketed or not marketed), with a possible effect on psoriasis vulgaris (e.g., alefacept, efalizumab, etanercept, iniximab, adalimumab) within three months prior to randomisation - Systemic treatment with all other therapies than biologics, with a possible effect on psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within four weeks prior to randomisation - Systemic treatment with VitaminD preparations above 500 IU per day - PUVA or Grenz ray therapy within four weeks prior to randomisation - UVB therapy within two weeks prior to randomisation - Any topical treatment of the trunk/limbs (except for emollients) within two weeks prior to randomisation - Topical treatment for other relevant skin disorders on the face and exures (e.g., facial and exural psoriasis, eczema) with potent or very potent (WHO group III-IV) corticosteroids or vitamin D analogues within two weeks prior to randomisation - Topical treatment for other relevant skin disorders on the scalp (e.g. scalp psoriasis) with very potent (WHO
254
Methods
Participants
Hoffmann
(Continued)
group IV) corticosteroids or vitamin D analogues within two weeks prior to randomisation - Planned initiation of, or changes to concomitant medication that could affect psoriasis vulgaris (e.g., beta blockers, ACE inhibitors, anti-malaria drugs, lithium) during the study - Current diagnosis of erythrodermic, exfoliative or pustular psoriasis - Subjects with any of the following conditions present on the treatment area: viral (e.g., herpes or varicella) lesions, fungal and bacterial skin infections, parasitic infections, skin manifestations in relation to syphilis or tuberculosis, rosacea, perioral dermatitis, acne vulgaris, atrophic skin, striae atrophicae, fragility of skin veins, ichthyosis, acne rosacea, ulcers and wounds - Known or suspected disorders of calcium metabolism associated with hypercalcaemia - Known or suspected severe renal insufciency or severe hepatic disorders - Known or suspected hypersensitivity to component(s) of the Investigational Products - Current participation in any other interventional clinical study - Subjects who have received treatment with any non-marketed drug substance (i.e. an agent which has not yet been made available for clinical use following registration) within the four week period prior to randomisation, except for biologics (three months) - Planned exposure to sun during the study that may affect psoriasis vulgaris - Previously randomised to this study - Subjects known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychotic state) - Females of child-bearing potential wishing to become pregnant during the study, or are breast-feeding, or not using an adequate method of contraception during the study - Females of child-bearing potential with positive pregnancy test at Visit 1 Interventions Drug: calcipotriol and betamethasone (LEO 80185 gel) Drug: LEO 80185 vehicle Drug: Tacalcitol ointment Subjects with Controlled disease (Clear or Almost Clear disease) according to Investigators global assessment of disease severity at week eight Week eight April 2008 Richard Langley, MD, Principal Investigator, Eastern Canada Cutaneous Research Associates Ltd Dusica Curcic, Ph.D tel: 905-747-2354 Dusica.curcic@leo-pharma.com
Outcomes
Starting date Contact information
Notes Holick Trial name or title Methods Participants Treatment of Psoriasis With Parathyroid Hormone Treatment, Randomized, Double-Blind, Placebo Control, Single Group Assignment, Safety/Efcacy Study Inclusion Criteria: - Active plaque psoriasis at least 10 percent BSA (body surface area) - Age 18 to 70 Exclusion Criteria: - Abnormalities of calcium metabolism
255
Holick
(Continued)
Drug: Parathyroid hormone ointment Participants with active plaque psoriasis will be withdrawn from systemic and topical medications. After washout, we will select active psoriatic lesions of at least 25 cm2 in size to receive either placebo ointment or a proprietary ointment containing PTH for eight weeks. We will see the participants every 2 weeks. We will evaluate the lesions by examination and digital photography at each visit and measure parameters of calcium metabolism periodically during the eight weeks. At the conclusion of the eight weeks, we will obtain punch biopsies from the treated lesions and from one lesion without treatment. If the participants elect, we will transition them into an open label trial with the PTH ointment including up to 1000 cm2 of psoriatic lesions and monitor them for duration of effect and changes in parameters of calcium metabolism
Starting date Contact information Notes Jemec Trial name or title Methods Participants
January 2000 Michael Holick, PhD, MD, Principal Investigator
Efcacy and Safety of Calcipotriol Plus Betamethasone Gel in the Treatment of Scalp Psoriasis Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efcacy Study Main Inclusion Criteria: - Scalp psoriasis amenable to topical treatment - Psoriasis vulgaris on trunk and/or limbs - Extent of scalp psoriasis involving more than 10% of the total scalp area - Disease severity on the scalp graded as mild or worse by the investigator - Consenting out-patients of 18 years or above Main Exclusion Criteria: - PUVA or Grenz ray therapy within four weeks prior to randomisation - UVB therapy within two weeks prior to randomisation - Systematic treatment with biological therapies, with a possible effect on scalp psoriasis within six months prior to randomisation - Systemic treatment with all other therapies than biologicals, with a possible effect on scalp psoriasis (e.g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within four weeks prior to randomisation - Any topical treatment of the scalp (except for medicated shampoos and emollients) within two weeks prior to randomisation - Topical treatment of the face, trunk and/or limbs with very potent WHO group IV corticosteroids within two weeks prior to randomisation - Current diagnosis of erythrodermic, exfoliative or pustular psoriasis Drug: Calcipotriol plus betamethasone dipropionate (LEO80185 gel)
256
Interventions
Jemec
(Continued)
Outcomes
Overall disease severity according to investigators assessment at week eight Total sign score at week eight Score for scaliness, redness and thickness at week eight Extent of scalp psoriasis at week eight Overall disease severity according to investigators assessment at week two and four Overall disease severity according to participants at week eight Adverse events Laboratory data November 2004 Gregor Jemec, MD, Principal Investigator, Roskilde Hospital, Division of Dermatology
Starting date Contact information Notes Kimball Trial name or title Methods
LCD Solution Versus Calcipotriol Cream in the Treatment of Moderate Plaque Psoriasis Treatment, Randomized, Single-Blind (Investigator), Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - 18 years of age or older - able and willing to provide written informed consent - diagnosed with chronic plaque psoriasis - 3% to 15% body surface area involved - in good general health Exclusion Criteria: - other current treatments for psoriasis - renal or liver dysfunction - pregnant or nursing Drug: LCD Drug: calcipotriol Difference in percent reduction in Psoriasis Area and Severity Index (PASI) Scores between treatment arms 12 weeks of treatment January 2007 Alexandra B Kimball, MD, Principal Investigator, Massachusettes General Hospital / Brigham Womens Hospital, Clinical Unit for Research Trials in Skin, Boston, Massachusetts, 02114 Maria-Beatrice Alora-Palli, MD tel: 617-726-5066
Participants
Interventions
Outcomes
Notes
257
Kragballe Trial name or title Methods Participants Efcacy of Calcipotriol Plus Betamethasone Gel Versus Calcipotriol Scalp Solution in Scalp Psoriasis Treatment, Randomized, Single-Blind, Active Control, Parallel Assignment, Safety/Efcacy Study Main Inclusion Criteria: - Scalp psoriasis amenable to topical treatment - Psoriasis vulgaris on trunk and/or limbs - Extent of scalp psoriasis involving more than 10% of the total scalp area - Disease severity on the scalp graded as moderate or worse by the investigator - Consenting out-patients of 18 years or above Main Exclusion Criteria: - PUVA or Grenz ray therapy within four weeks prior to randomisation - UVB therapy within two weeks prior to randomisation - Systemic treatment with biological therapies, with a possible effect on scalp psoriasis within six months prior to randomisation - Systemic treatment with all other therapies than biologicals, with a possible effect on scalp psoriasis (e.g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within four weeks prior to randomisation - Any topical treatment of the scalp (except for non steroid medicated shampoos and emollients) within two weeks prior to randomisation - Topical treatment of the face, trunk and/or limbs with very potent WHO group IV corticosteroids within two weeks prior to randomisation - Current diagnosis of erythrodermic, exfoliative or pustular psoriasis Calcipotriol plus betamethasone dipropionate (LEO80185 gel) Overall disease severity according to investigators assessment at week eight Total sign score at week eight Score for redness, thickness and scaliness at week eight Overall disease severity according to the investigators assessment at week two and four Overall disease severity according to participants at week eight Relapse and rebound during the study May 2006 Knud Kragballe, MD, Principal Investigator, Department of Dermatology, Marselisborg Centres
Starting date Contact information Notes Luger Trial name or title Methods Participants
Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel for up to a Year in Scalp Psoriasis Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Scalp psoriasis amenable to topical treatment with a maximum of 100 g of study medication per week - Clinical signs of psoriasis vulgaris on trunk and/or limbs, or earlier diagnosed with psoriasis vulgaris on
258
Luger
(Continued)
trunk and/or limbs - Extent of scalp psoriasis involving more than 10% of the total scalp area - Disease severity on the scalp graded as Moderate, Severe or Very Severe according to the Investigators Global Assessment of disease severity Exclusion Criteria: - PUVA or Grenz ray therapy anywhere on the participant within 28 days prior to randomisation - UVB therapy anywhere on the participant within 14 days prior to randomisation - Systemic use of biological treatments, whether marketed or not, directed against or with a potential effect on, scalp psoriasis (e.g., alefacept, efalizumab, etanercept, iniximab) within six months prior to randomisation - Systemic treatments with a potential effect on scalp psoriasis vulgaris (e.g., corticosteroids, retinoids, immunosuppressants) within 28 days prior to randomisation - Any topical treatment for scalp psoriasis or any other skin disease on the scalp (excluding medicated shampoos, emollients and hair conditioners) within 14 days prior to randomisation - Topical treatment for other skin disorders with very potent WHO group IV corticosteroids within 14 days prior to randomisation - Planned initiation of, or changes in dose of concomitant medication that could affect scalp psoriasis (e.g., beta blockers, antimalarial drugs, lithium) during the study - Current diagnosis of guttate, pustular, exfoliative or erythrodermic psoriasis - Participant with any of the following conditions present on the scalp area: viral lesions, fungal and bacterial skin infections, parasitic infections and atrophic skin - Known or suspected severe renal insufciency or severe hepatic disorders - Patiens with history/signs/symptoms suggestive of an abnormality of calcium homeostasis associated with clinically signicant hypercalcaemia - Trial subjects should be using an adequate method of contraception Interventions Outcomes Drug: Calcipotriol plus betamethasone dipropionate gel (LEO 80185) The proportions of participants who experience adverse drug reactions and the proportion of participants who experience adverse events of concern associated with long-term topical corticosteroid use on the scalp during the study February 2005 T A Luger, Dr. med., Principal Investigator, Universitatsklinikum Muenster, Klinik und Poliklinik fur Hautkrankheiten
Notes Lukic Trial name or title Methods A Safety and Efcacy Study of a Topical Gel for the Treatment of Mild to Moderate Psoriasis Treatment, Randomized, Double-blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Mentally competent and has completed an appropriately administered informed consent. - Male or non-pregnant female outpatient between the ages of 18 to 65 years.
259
Participants
Lukic
(Continued)
- If subject is a woman of childbearing potential, she must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline, and agree to use an effective, non-prohibited form of birth control for the duration of the study (stabilized on hormonal contraceptives for at least two months (e.g. oral, implant, injection, NuvaRing, patch), IUD, condom and spermicidal or diaphragm and spermicidal, abstinence, etc.). - Willing and able to apply the assigned study medication as directed, comply with study instructions and commit to all follow-up visits for the duration of the study. - Clinical diagnosis of stable plaque psoriasis for at least three months. - Plaque psoriasis with a minimum of 2% affected BSA (excluding palms, soles, face, scalp, groin, axillae or other intertriginous areas). - Subjects disease is suitable to be managed topically for the duration of the trial. - Subject has a Target Plaque that must have: - a minimum of 16 cm2 in area - an Overall DiseaseSeverity Score of 2 or 3 - an induration score of 2 or 3 - Willing and able to avoid prolonged exposure of the designated treatment lesions to ultraviolet radiation (natural and articial) for the duration of the study. - In good general health and free of any disease state or physical condition which might impair evaluation of plaque psoriasis or which, in the investigators opinion, exposes the subject to an unacceptable risk by study participation. Exclusion Criteria: - Female who is lactating, or is planning to become pregnant during the study. - Has spontaneously improving or rapidly deteriorating plaque psoriasis. - Has guttate, pustular, erythrodermic, inverse or other non-plaque forms of psoriasis. - Has used any psoriasis vaccine or has participated in an investigational study of any psoriasis vaccine. - Has used any systemic immunomodulatory therapy known to affect psoriasis that DOES typically decrease immune cell populations (e.g. alefacept) within the 36 weeks prior to start of treatment. - Subject has used any systemic immunomodulatory therapy known to affect psoriasis that DOES NOT typically decrease immune cell populations (e.g. efalizumab, etanercept, iniximab, adalimumab, and any investigational anti-TNF or anti-IL-12/23 agents) within 12 weeks prior to start of treatment. - Has used any photo-therapy (including laser), photo-chemotherapy or systemic psoriasis therapy (e.g. systemic corticosteroids, methotrexate, retinoids or cyclosporine) within four weeks prior to start of treatment. - Prolonged exposure to natural or articial sources (e.g. UVB, UVA, etc.) of ultraviolet radiation within four weeks prior to the start of treatment or is intending to have such exposure during the study, thought by the investigator likely to modify the subjects psoriasis. - Has used topical anti-psoriatic therapy (including topical retinoids, corticosteroids, vitamin D derivatives, topical immunomodulators, coal tar or salicylic acid preparations) on the areas to be treated within two weeks prior to start of treatment. - Has used emollients/moisturizers on areas to be treated within two days prior to the start of treatment. - Has used lithium or hydroxychloroquine within four weeks prior to start of treatment. - Currently using a beta-blocking medication (e.g. propranolol) with a dose that has not been stabilized for at least three months prior to the start of treatment. - Has recently been on medications for osteoporosis including but not limited to bisphosphonates, calcitonin, teriparatide, androgen or other anabolic steroid therapy, uorides, vitamin D > 50,000 IU/week, within the past 6 months. - May be unreliable including subjects who engage in excessive alcohol intake or drug abuse. - Subject has, in the opinion of the investigator, any clinically signicant abnormalities in the clinical labo-
260
Lukic
(Continued)
ratory tests (serum chemistries, hematology or urinalysis) conducted at screening.- Subject has a history of hypercalcemia (consistent with elevated serum calciums above 10.5 mg/dl), illnesses that affect bone or calcium metabolism or recent nephrolithiasis or urolithiasis (within the previous 2 years). - Has a history of radiation therapy involving the skeleton. - Has a history of sensitivity to any of the ingredients in the study medications. - Currently enrolled in an investigational drug or device study. - Has used an investigational drug or an investigational device treatment within 30 days prior to start of treatment Interventions Outcomes Drug: PTH (1-34) Gel / Placebo Gel All efcacy variables graded will be evaluated. Individual parameters of psoriasis include Erythema (0 to 4 scale); Scaling (0 to 4 scale); Induration (0 to 4 scale); Pruritus (0 to 3 scale); and Overall Disease Severity Score (0 to 4 scale). Weeks one to eight October 2007 Tatjana Lukic, M.D., M.Sc., Study Chair, Manhattan Pharmaceuticals, Inc
Starting date Contact information Notes Poulin Trial name or title Methods
Maintenance Effect of Clobex Shampoo on Subjects With Moderate to Severe Scalp Psoriasis Treatment, Randomized, Double-blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efcacy Study Inclusion Criteria: - Male or female subjects aged 18 years or older. - Subjects with moderate to severe scalp psoriasis Exclusion Criteria: - Subjects who need systemic treatment for their body psoriasis - Subjects with a washout period for topical treatment(s) on the scalp less than: - Corticosteroids two weeks - All other anti-psoriasis medications two weeks - Subjects with a washout period for systemic treatment(s) less than: - PUVA therapy four weeks - Biological therapies 12 weeks - Treatments other than biologicals with a possible efcacy on psoriasis four weeks - Treatment known to worsen psoriasis two weeks Drug: Clobex Shampoo 0.05% Drug: clobex shampoo placebo Global severity score 1st relapse September 2006
261
Participants
Interventions
Outcomes Starting date
Poulin
(Continued)
Contact information Notes QuatRx Trial name or title Methods Participants
Poulin, MD, Principal Investigator, Centre de Recherche Dermatologique du Quebec Metropolitain
Safety and Efcacy Study of Two Dose Regimens of Becocalcidiol in the Treatment of Plaque-Type Psoriasis Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Clinical diagnosis of stable plaque-type psoriasis affecting 2% to 10% of the subjects body surface area - Psoriasis of a severity that is appropriate for treatment with topical therapy; PGA of at least three (moderate) at baseline; PSS of at least seven, and with no individual symptom score (erythema, induration, or scaling) less than two - Subject must sign the IRB approved informed consent and agree to follow dosing instructions and complete required clinic visits. Exclusion Criteria: - Pregnant or nursing females - Systemic corticosteroids, methotrexate, cyclosporine, systemic retinoids, prolonged sun exposure or ultraviolet light therapy within four weeks of dosing - Topical corticosteroids, retinoids, calcipotriene, coal tar, anthralin, or any other treatment indicated for psoriasis within two weeks of dosing - Untreated bacterial, tubercular, fungal or any viral lesion of the skin - Biologic agents/monoclonal antibodies in the last six months - Currently using lithium or plaquenil - Currently using a beta-blocking medication or thiazide diuretic and the dose has not been stabilized for at least six months - History of hypercalcemia or evidence of vitamin D toxicity - Current or history of melanoma skin cancer in the past ve years Drug: Vehicle (Placebo) applied BID Drug: QRX-101 75 mcg/g ointment applied QD Drug: QRX-101 75 mcg/g ointment applied BID Dichotomized Physicians Static Global Assessment of Overall Lesion Severity (PGA) at Week eight Percent Change from Baseline in Psoriasis Symptom Severity (PSS)Scale at Week eight September 2004 Not supplied
Interventions
Outcomes
Starting date Contact information Notes
262
Theobald Trial name or title Methods Study of Dose-Effect of COL-121 Ointment in Patients With Plaque-Type Psoriasis Treatment, Randomized, Double-blind (Subject, Outcomes Assessor), Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Psoriasis must affect at least 2% and not more than 10% of the subjects body surface area, excluding the face and scalp - Subject must have two to four target plaques on the area to be treated, excluding the face and scalp. - Subjects who are women of childbearing potential must have a negative pregnancy test and be non-lactating. - Subjects who are women of childbearing potential must utilize one of the following methods of birth control throughout the study: IUD, diaphragm, a condom, a spermicidal gel or foam, oral contraceptives (provided subject has been utilizing this method for at least four months prior to Visit 1 and has not changed the brand within this period). - Subjects may also participate if they are surgically sterilized, in a monogamous relationship with a sterile partner, or abstain from sexual intercourse during the course of the study. - Subjects must be in good general health and free of any disease state or physical condition that, in the investigators opinion, may interfere with study evaluations or exposes the subject to unacceptable risk by study participation. - Subject must be willing and able to apply the study medication as directed, comply with the study instructions, and commit to all the follow-up visits for the duration of the study. - Subjects must sign an informed consent form. Exclusion Criteria: - Subjects who have guttate, pustular, erythrodermic or other non-plaque types of psoriasis. - Subjects who have spontaneously improving or rapidly deteriorating plaque psoriasis. - Subjects who have used systemic immunomodulatory therapy known to affect psoriasis and to typically decrease immune cell populations (e.g., alefacept) within the previous 40 weeks. - Subjects who have used any systemic immunomodulatory therapy known to affect psoriasis and to NOT typically decrease immune cell populations (e.g., etanercept) within the previous 16 weeks. - Subjects who have used any photo-therapy (including laser), photo-chemotherapy or systemic psoriasis therapy (e.g., systemic corticosteroids, methotrexate, retinoids, cyclosporine) within the previous 12 weeks. - Subjects who have had prolonged exposure to natural or articial sources of ultraviolet radiation within the previous three weeks or are intending to have such exposure during the study, thought by the investigator likely to modify the subjects plaque psoriasis. - Subjects who have used topical anti-psoriatic therapy (including topical retinoids) on the areas to be evaluated within the previous two weeks. - Subjects who have used emollients/moisturizers on the areas to be evaluated within the previous 1 day. - Subjects who have untreated bacterial, tubercular, fungal or viral lesions of the skin on the areas to be evaluated. - Subjects who have known sensitivity to a component of the study medication or to topical or systemic vitamin D. - Subjects who have any signicant condition such as diseases of the hepatic, renal, endocrine, musculoskeletal, or nervous system, or any gross physical impairment. - Subjects who have taken a vitaminD supplement that exceeds 400 IU per day in the previous 30 days. - Subjects who have taken a calcium supplement that exceeds 1200 mg per day in the previous 30 days. - Subjects who are using lithium or Plaquenil. - Subjects who are using beta-blocking medication or thiazide diuretics whose dose has not been stable for at least 12 weeks. - Subjects who have a history of hypercalcemia or evidence of vitamin D toxicity.
Participants
263
Theobald
(Continued)
- Subjects who are currently being treated for malignancy or have been diagnosed with melanoma within the past 5 years. - Subjects who have received any investigational treatment(s) within the previous 30 days Interventions Drug: COL-121 Drug: 50g/g Calcipotriene Ointment Drug: Placebo Physicians Global Assessment Randomization and Day 84 January 2008 Klaus P Theobald, MD, Study Chair, CollaGenex Pharmaceuticals
Outcomes Starting date Contact information Notes van de Kerkhof Trial name or title Methods Participants
Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Gel in Scalp Psoriasis Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Scalp psoriasis amenable to topical treatment with a maximum of 100 g of medication per week - Clinical signs of psoriasis vulgaris on trunk and/or limbs, or earlier diagnosed with psoriasis vulgaris on trunk and/or limbs - Extent of scalp psoriasis involving more than 10% of the total scalp area - Investigators assessment of clinical signs of the scalp of at least 2 in one of the clinical signs, erythema, thickness and scaliness, and at least 1 in each of the other two clinical signs - Disease severity on the scalp graded as Mild, Moderate, Severe or Very severe according to the investigators global assessment of disease severity Exclusion Criteria: - PUVA or Grenz ray therapy within four weeks prior to randomisation - UVB therapy within two weeks prior to randomisation - Systemic treatment with biological therapies, with a possible effect on scalp psoriasis within six months prior to randomisation - Systemic treatment with all other therapies than biologicals, with a possible effect on scalp psoriasis (e.g., corticosteroids, vitamin D analogues, retinoids, immunosuppressants) within four weeks prior to randomisation - Any topical treatment of the scalp (except for medicated shampoos and emollients) within two weeks prior to randomisation - Topical treatment of the face, trunk and/or limbs with very potent WHO group IV corticosteroids within two weeks prior to randomisation - Current diagnosis of erythrodermic, exfoliative or pustular psoriasis Drug: Calcipotriol plus betamethasone dipropionate (LEO80185 gel)
Interventions
264
van de Kerkhof
(Continued)
Outcomes
Participant with Controlled disease (Absence of disease or Very mild disease) according to investigators global assessment of disease severity at week eight December 2004 Peter van de Kerkhof, MD, Principal Investigator, Universitair Medisch, Afdeling Dermatologie
Starting date Contact information Notes White Trial name or title
Efcacy and Safety of Calcipotriol Cream and (Calcipotriol + Betamethasone Dipropionate) Ointment in Psoriasis Vulgaris Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efcacy Study Participant with psoriasis vulgaris of trunk and/or limbs Drug: Calcipotriol, (calcipotriol + betamethasone) A phase IV study of different treatment regimens a. Four weeks of ointment containing calcipotriol and betamethasone dipropionate followed by eight weeks of calcipotriol cream b. Four weeks of (calcipotriol plus betamethasone dipropionate) ointment followed by eight weeks of calcipotriol cream on weekdays/ (calcipotriol plus betamethasone dipropionate) ointment on weekends c. Four weeks of (calcipotriol plus betamethasone dipropionate) ointment followed by eight weeks of vehicle of calcipotriol cream
Methods Participants Interventions
Outcomes Starting date Contact information Notes Wozel Trial name or title Methods
Efcacy of regimen (a) versus regimen (c) by % change in PASI at week 12 April 2005 S White, MD, Principal Investigator, Clatterbridge Hospital, Department of Dermatology
Evaluation of Topical Antipsoriatics in the Psoriasis Plaque Test Treatment, Randomized, Double-blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Single Group Assignment, Efcacy Study Inclusion Criteria: - Participants with psoriasis vulgaris older than 18 Years - Negative urine pregnancy test
265
Participants
Wozel
(Continued)
- Written informed consent - Good compliance Exclusion Criteria: - Participants less than 18 years - Pregnant participants - Participants with renal insufciency, liver diseases - Participants who received systemic antipsoriatic treatment or UV treatment less than four weeks prior to study - Participants who used topical antipsoriatics within two weeks prior to study - Immunosuppressed Participants Interventions Outcomes Starting date Contact information Notes Yin-ku Lin Trial name or title Randomised, observer-blinded, vehicle-controlled trial on the efcacy and safety of a topical indigo naturalise ointment treatment for recalcitrant psoriasis vulgaris Randomised, double-blind, placebo-controlled, intra-patient comparison Please note that as of 10/04/2007 the trial study design was changed to: Randomised, observer-blinded, placebo-controlled, intra-patient comparison 1. Participants with bilateral symmetric, chronic plaque-type psoriasis 2. Participants who have a history of plaque psoriasis for a minimum of two years 3. Participants who have a history of resistance to at least two topical treatments (e.g. corticosteroid and vitamin D3 analogues) 4. Participants who have good general health and normal full blood picture, renal, and liver function in tests done before starting the study 5. Participants of childbearing age who agree to continue using birth control measures for the duration of the study 6. Males and females between 18 and 75 years Topical indigo naturalise ointment Clinical and laboratory assessments were done at baseline and every two weeks thereafter until 12 weeks after the start therapy. The changes in Erythema, Scaling, Indurations (ESI) and bilateral plaque areas are recorded from the beginning to end of the treatments. Erythema (redness), scaling and indurations (thickening), are scored on a 0 to 8 scale (where 0 = none and 8 = very severe); the sum of these scores for each target lesion is the ESI score. The bilateral plaque area is rated from of 0% to 100% (0% = clearance and 100% = baseline) topical therapies Protopic and Advantan as well as their combination against placebo Psoriasis Plaque Test: sum score of psoriasis plaque tests on day 11 September 2004 Gottfried Wozel, Professor, Principal Investigator, Technische Universitat Dresden
Methods
Participants
266
Yin-ku Lin
(Continued)
01/05/2004 Dr Yin-ku Lin, lin1266@adm.cgmh.org.tw 123 Ding-Hu road Kuei-Shan Taoyuan Taiwan 333
Notes Zheng Trial name or title Efcacy and Safety of Calcipotriol Plus Betamethasone Dipropionate Ointment in Patients With Psoriasis Vulgaris Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efcacy Study Inclusion Criteria: - Clinical diagnosis of psoriasis vulgaris in a stable condition - Extent of at least 10% of one or more body regions - Amenable to topical therapy with maximum of 100 g/week of investigational product Exclusion Criteria: - Participants with more than 30% of body surface area involved - Participants with facial psoriasis who need treatment - Participants who need treatment of scalp psoriasis with WHO group IV topical corticosteroids, tretinoin or topical vitamin D derivatives - Participants with unstable forms of psoriasis including guttate, erythrodermic, pustular, or arthritis psoriasis - Systemic treatment of psoriasis with corticosteroids or other therapy - Systemic antipsoriatic treatment (e.g. corticosteroids, immunosuppressive drugs, tretinoin, antibiotics, phototherapy or calcium agents) within four weeks prior to visit 1; or topical antipsoriatic treatment (e.g. keratolytics, topical corticosteroids, topical vitamin D derivatives, anthralin, crude coal tar, etc) within the previous 2 week period - Participants with planned exposure to phototherapy that may affect the psoriasis during the study period Drug: Calcipotriol plus betamethasone dipropionate ointment The percentage change of PASI at the end of week four compared with baseline October 2005 Zheng Zhi Zhong, Professor, Principal Investigator, Fudan University First Hospital, Dermatology Department
Methods Participants
Interventions Outcomes Starting date Contact information
Notes
267
DATA AND ANALYSES
Comparison 1. Vitamin D analogues vs. placebo
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol 1.2 Calcitriol 1.3 Tacalcitol 1.4 Dovobet, OD 1.5 Dovobet, BD 1.6 Maxacalcitol 1.7 Paricalcitol OD 2 TSS 2.1 Calcipotriol 2.2 Calcitriol 2.3 Tacalcitol 2.4 Dovobet, OD 2.5 Dovobet, BD 2.6 Maxacalcitol 2.7 Paricalcitol OD 3 PASI 3.1 Calcipotriol 3.2 Calcitriol 3.3 Tacalcitol 3.4 Dovobet, OD 3.5 Dovobet, BD 3.6 Maxacalcitol 3.7 Paricalcitol OD 4 PAGI 4.1 Calcipotriol 4.2 Calcitriol 4.3 Tacalcitol 4.4 Dovobet, OD 4.5 Dovobet, BD 4.6 Maxacalcitol 4.7 Paricalcitol OD 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol 5.2 Calcitriol 5.3 Tacalcitol 5.4 Dovobet, OD 5.5 Dovobet, BD 5.6 Maxacalcitol 5.7 Paricalcitol OD 6 Total withdrawals 6.1 Calcipotriol
No. of studies 15 9 4 1 1 2 1 1 16 10 2 3 1 0 1 1 7 7 0 0 2 2 0 0 3 3 0 0 0 0 0 0 24 15 5 3 2 2 1 1 21 12
No. of participants 3451 1597 319 206 356 848 103 22 3048 1592 188 496 647 0 103 22 3946 2093 0 0 1004 849 0 0 488 488 0 0 0 0 0 0 5725 2914 339 496 1003 848 103 22 5294 2367
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size -1.30 [-1.57, -1.03] -1.04 [-1.27, -0.82] -1.25 [-2.63, 0.12] -1.13 [-1.42, -0.83] -1.58 [-1.82, -1.33] -1.90 [-2.09, -1.71] -1.43 [-1.91, -0.96] -1.66 [-2.66, -0.67] -1.28 [-1.60, -0.95] -1.13 [-1.43, -0.83] -2.06 [-5.94, 1.82] -0.66 [-0.95, -0.37] -1.31 [-1.51, -1.12] Not estimable -1.61 [-2.10, -1.12] -2.15 [-3.24, -1.06] -0.91 [-1.18, -0.64] -0.66 [-0.76, -0.56] Not estimable Not estimable -1.38 [-2.02, -0.73] -1.41 [-1.86, -0.97] Not estimable Not estimable -0.72 [-1.01, -0.42] -0.72 [-1.01, -0.42] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable -1.17 [-1.38, -0.96] -1.02 [-1.21, -0.83] -1.03 [-2.25, 0.19] -0.82 [-1.34, -0.29] -1.43 [-1.69, -1.18] -1.90 [-2.09, -1.71] -1.43 [-1.91, -0.96] -1.66 [-2.66, -0.67] -0.03 [-0.06, -0.01] -0.04 [-0.06, -0.01]
268
6.2 Calcitriol 6.3 Tacalcitol 6.4 Dovobet, OD 6.5 Dovobet BD 6.6 Maxacalcitol 6.7 Paricalcitol OD 7 Withdrawals due to adverse events 7.1 Calcipotriol 7.2 Calcitriol 7.3 Tacalcitol 7.4 Dovobet, OD 7.5 Dovobet BD 7.6 Maxacalcitol 7.7 Paricalcitol OD 8 Withdrawals due to treatment failure 8.1 Calcipotriol 8.2 Calcitriol 8.3 Tacalcitol 8.4 Dovobet, OD 8.5 Dovobet BD 8.6 Maxacalcitol 8.7 Paricalcitol OD 9 Adverse events (local) 9.1 Calcipotriol 9.2 Calcitriol 9.3 Tacalcitol 9.4 Dovobet, OD 9.5 Dovobet BD 9.6 Maxacalcitol 9.7 Paricalcitol OD 10 Adverse events (systemic) 10.1 Calcipotriol 10.2 Calcitriol 10.3 Tacalcitol 10.4 Dovobet, OD 10.5 Dovobet BD 10.6 Maxacalcitol 10.7 Paricalcitol OD
5 3 2 2 1 1 20 11 5 3 2 1 1 1 11 5 4 1 1 1 1 1 15 11 2 1 2 2 0 1 12 8 2 1 0 1 1 1
339 582 1007 857 120 22 4746 2234 339 582 1006 443 120 22 2603 1064 281 314 359 443 120 22 4798 2546 78 291 1006 855 0 22 2206 1182 226 244 0 412 120 22
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.00 [-0.02, 0.02] Not estimable -0.11 [-0.16, -0.07] -0.07 [-0.12, -0.03] 0.11 [-0.01, 0.23] Not estimable -0.02 [-0.05, -0.00] -0.02 [-0.04, -0.00] -0.00 [-0.02, 0.02] 0.01 [-0.01, 0.02] -0.09 [-0.12, -0.06] -0.10 [-0.14, -0.05] -0.01 [-0.08, 0.06] Not estimable -0.05 [-0.10, -0.01] -0.08 [-0.11, -0.05] -0.03 [-0.12, 0.05] Not estimable -0.09 [-0.13, -0.05] -0.09 [-0.13, -0.05] -0.03 [-0.11, 0.04] Not estimable -0.01 [-0.02, 0.01] 0.01 [-0.01, 0.04] Not estimable -0.01 [-0.03, 0.02] -0.05 [-0.10, -0.01] -0.03 [-0.08, 0.01] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable
Comparison 2. Corticosteroid (potent) vs. placebo
Outcome or subgroup title 1 IAGI 1.1 Betamethasone dipropionate, maintenance
No. of studies 11 0
No. of participants 1269 0
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size -1.09 [-1.26, -0.92] Not estimable

269
1.2 Betamethasone dipropionate OD 1.3 Betamethasone dipropionate BD 1.4 Betamethasone valerate 1.5 Budesonide 1.6 Desonide 1.7 Diorasone diacetate 1.8 Fluticasone propionate 1.9 Hydrocortisone buteprate 1.10 Mometasone furoate 1.11 Fluocinolone acetonide, plus occlusion 2 TSS 2.1 Betamethasone dipropionate, maintenance 2.2 Betamethasone dipropionate OD 2.3 Betamethasone dipropionate BD 2.4 Betamethasone valerate 2.5 Budesonide 2.6 Desonide 2.7 Diorasone diacetate 2.8 Fluticasone propionate 2.9 Hydrocortisone buteprate 2.10 Mometasone furoate 2.11 Fluocinolone acetonide, plus occlusion 3 PASI 3.1 Betamethasone dipropionate, maintenance 3.2 Betamethasone dipropionate OD 3.3 Betamethasone dipropionate BD 3.4 Betamethasone valerate 3.5 Budesonide 3.6 Desonide 3.7 Diorasone diacetate 3.8 Fluticasone propionate 3.9 Hydrocortisone buteprate 3.10 Hydrocortisone buteprate 3.11 Fluocinolone acetonide, plus occlusion 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Betamethasone dipropionate, maintenance
0 5 1 0 1 0 2 0 1 1 12 1 2 2 3 0 1 1 0 1 1 1 2 0 1 1 0 0 0 0 0 0 0 0 0 17 1
0 557 74 0 76 0 383 0 95 84 1594 38 726 53 268 0 76 93 0 161 95 84 1052 0 633 419 0 0 0 0 0 0 0 0 0 2481 38
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Not estimable -1.34 [-1.54, -1.14] -1.41 [-1.93, -0.90] Not estimable -0.87 [-1.40, -0.34] Not estimable -0.93 [-1.14, -0.72] Not estimable -0.75 [-1.17, -0.34] -1.22 [-1.69, -0.76] -0.84 [-1.01, -0.67] -1.00 [-1.68, -0.32] -0.83 [-1.00, -0.66] -0.73 [-1.28, -0.17] -1.15 [-1.47, -0.83] Not estimable -1.14 [-1.69, -0.60] -0.34 [-0.75, 0.07] Not estimable -0.46 [-0.77, -0.15] -1.18 [-1.62, -0.74] -0.89 [-1.34, -0.44] -1.14 [-1.29, -0.99] Not estimable -1.09 [-1.28, -0.90] -1.21 [-1.44, -0.97] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable -0.95 [-1.11, -0.80] -1.00 [-1.68, -0.32]
270
5.2 Betamethasone dipropionate OD 5.3 Betamethasone dipropionate BD 5.4 Betamethasone valerate 5.5 Budesonide 5.6 Desonide 5.7 Diorasone diacetate 5.8 Fluticasone propionate 5.9 Hydrocortisone buteprate 5.10 Mometasone furoate 5.11 Fluocinolone acetonide, plus occlusion 6 Total withdrawals 6.1 Betamethasone dipropionate, maintenance 6.2 Betamethasone dipropionate OD 6.3 Betamethasone dipropionate BD 6.4 Betamethasone valerate 6.5 Budesonide 6.6 Desonide 6.7 Diorasone diacetate 6.8 Fluticasone propionate 6.9 Hydrocortisone buteprate 6.10 Mometasone furoate 6.11 Fluocinolone acetonide, plus occlusion 7 Withdrawals due to adverse events 7.1 Betamethasone dipropionate, maintenance 7.2 Betamethasone dipropionate OD 7.3 Betamethasone dipropionate BD 7.4 Betamethasone valerate 7.5 Budesonide 7.6 Desonide 7.7 Diorasone diacetate 7.8 Fluticasone propionate 7.9 Hydrocortisone buteprate 7.10 Mometasone furoate 7.11 Fluocinolone acetonide, plus occlusion 8 Withdrawals due to treatment failure 8.1 Betamethasone dipropionate, maintenance
2 5 3 0 1 1 2 1 1 1 8 1 1 1 1 1 1 0 0 1 0 1 11 2 1 2 2 1 1 0 0 1 1 0 6 2
726 557 268 0 76 93 383 161 95 84 1545 40 633 421 80 22 80 0 0 180 0 89 1484 134 633 53 252 22 80 0 0 190 120 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.83 [-1.00, -0.66] -1.34 [-1.54, -1.14] -1.22 [-1.50, -0.95] Not estimable -0.87 [-1.40, -0.34] -0.34 [-0.75, 0.07] -0.93 [-1.14, -0.72] -0.46 [-0.77, -0.15] -0.75 [-1.17, -0.34] -1.22 [-1.69, -0.76] -0.07 [-0.13, -0.01] -0.5 [-0.77, -0.23] -0.11 [-0.17, -0.05] -0.06 [-0.12, 0.01] Not estimable Not estimable -0.18 [-0.38, 0.02] Not estimable Not estimable 0.00 [-0.09, 0.10] Not estimable -0.04 [-0.13, 0.04] -0.01 [-0.04, 0.02] Not estimable -0.07 [-0.11, -0.02] Not estimable 0.03 [-0.07, 0.13] Not estimable -0.1 [-0.24, 0.04] Not estimable Not estimable 0.01 [-0.02, 0.04] -0.05 [-0.11, 0.01] Not estimable Subtotals only -0.46 [-0.61, -0.31]
130
Risk Difference (M-H, Random, 95% CI)
271
8.2 Betamethasone dipropionate OD 8.3 Betamethasone dipropionate BD 8.4 Betamethasone valerate 8.5 Budesonide 8.6 Desonide 8.7 Diorasone diacetate 8.8 Fluticasone propionate 8.9 Hydrocortisone buteprate 8.10 Mometasone furoate 8.11 Fluocinolone acetonide, plus occlusion 9 Adverse events (local) 9.1 Betamethasone dipropionate, maintenance 9.2 Betamethasone dipropionate OD 9.3 Betamethasone dipropionate BD 9.4 Betamethasone valerate 9.5 Budesonide 9.6 Desonide 9.7 Diorasone diacetate 9.8 Fluticasone propionate 9.9 Hydrocortisone buteprate 9.10 Mometasone furoate 9.11 Fluocinolone acetonide, plus occlusion 10 Adverse events (systemic) 10.1 Betamethasone dipropionate, maintenance 10.2 Betamethasone dipropionate OD 10.3 Betamethasone dipropionate BD 10.4 Betamethasone valerate 10.5 Budesonide 10.6 Desonide 10.7 Diorasone diacetate 10.8 Fluticasone propionate 10.9 Hydrocortisone buteprate 10.10 Mometasone furoate 10.11 Fluocinolone acetonide, plus occlusion
0 0 1 1 1 0 0 1 0 0 11 2 1 3 0 0 1 0 1 1 1 1 2 0 0 1 0 0 0 0 0 0 1 0
0 0 80 22 80 0 0 190 0 0 2103 134 633 474 0 0 80 0 383 190 120 89 541 0 0 421 0 0 0 0 0 0 120 0
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable -0.02 [-0.06, 0.01] Not estimable -0.09 [-0.14, -0.03] -0.04 [-0.10, 0.02] Not estimable Not estimable Not estimable Not estimable 0.00 [-0.05, 0.05] -0.06 [-0.18, 0.07] -0.10 [-0.23, 0.02] 0.02 [-0.04, 0.08] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable
272
Comparison 3. Corticosteroid (very potent) vs. placebo

No. of studies 5 1 2 1 1 6 1 5 0 0 0 4 1 1 0 2 11 1 6 1 3 9 1 6 1 1 11 1 6 1 3 9 1 6 0 2 8 0 5 1 2 6 0 3 No. of participants 711 132 456 54 69 1186 126 1060 0 0 0 619 132 79 0 408 1802 132 1139 54 477 1524 165 1157 58 144 1944 165 1157 58 564 1666 165 1157 0 344 1446 0 968 58 420 1104 0 528
Outcome or subgroup title 1 IAGI 1.1 Amcinonide 1.2 Clobetasol propionate 1.3 Halcinonide 1.4 Halobetasol 2 TSS 2.1 Amcinonide 2.2 Clobetasol propionate 2.3 Halcinonide 2.4 Halobetasol 3 PASI 4 PAGI 4.1 Amcinonide 4.2 Clobetasol propionate 4.3 Halcinonide 4.4 Halobetasol 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Amcinonide 5.2 Clobetasol propionate 5.3 Halcinonide 5.4 Halobetasol 6 Total withdrawals 6.1 Amcinonide 6.2 Clobetasol propionate 6.3 Halcinonide 6.4 Halobetasol 7 Withdrawals due to adverse events 7.1 Amcinonide 7.2 Clobetasol propionate 7.3 Halcinonide 7.4 Halobetasol 8 Withdrawals due to treatment failure 8.1 Amcinonide 8.2 Clobetasol propionate 8.3 Halcinonide 8.4 Halobetasol 9 Adverse events (local) 9.1 Amcinonide 9.2 Clobetasol propionate 9.3 Halcinonide 9.4 Halobetasol 10 Adverse events (systemic) 10.1 Amcinonide 10.2 Clobetasol propionate
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size -1.42 [-1.72, -1.11] -1.42 [-1.80, -1.04] -1.32 [-2.07, -0.57] -1.11 [-1.69, -0.53] -1.81 [-2.37, -1.24] -1.24 [-1.38, -1.11] -1.31 [-1.70, -0.92] -1.23 [-1.39, -1.07] Not estimable Not estimable Not estimable -1.16 [-1.34, -0.99] -0.97 [-1.33, -0.61] -1.01 [-1.55, -0.47] Not estimable -1.25 [-1.46, -1.04] -1.29 [-1.45, -1.13] -1.42 [-1.80, -1.04] -1.24 [-1.50, -0.98] -1.11 [-1.69, -0.53] -1.36 [-1.65, -1.07] -0.02 [-0.06, 0.02] -0.00 [-0.11, 0.11] -0.03 [-0.09, 0.02] Not estimable Not estimable -0.00 [-0.01, 0.01] 0.01 [-0.02, 0.04] -0.00 [-0.01, 0.01] Not estimable Not estimable -0.01 [-0.04, 0.01] -0.01 [-0.05, 0.02] -0.02 [-0.06, 0.01] Not estimable Not estimable -0.00 [-0.02, 0.01] Not estimable -0.01 [-0.05, 0.03] -0.03 [-0.12, 0.06] Not estimable -0.00 [-0.01, 0.01] Not estimable -0.01 [-0.03, 0.01]
273
10.3 Halcinonide 10.4 Halobetasol
1 2
156 420
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable
Comparison 4. Dithranol vs. placebo
Outcome or subgroup title 1 IAGI 2 TSS 3 PASI 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 6 Total withdrawals 7 Withdrawals due to adverse events 8 Withdrawals due to treatment failure 9 Adverse events (local) 10 Adverse events (systemic)
No. of studies 1 3 0 0 3 4 3 2 3 1
No. of participants 16 94 0 0 94 124 104 44 94 20
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size -1.14 [-2.22, -0.06] -1.06 [-1.66, -0.46] Not estimable Not estimable -1.05 [-1.65, -0.46] Not estimable Not estimable Not estimable 0.26 [-0.30, 0.82] Not estimable
Comparison 5. Tazarotene vs. placebo
Outcome or subgroup title 1 IAGI 2 TSS 3 PASI 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 6 Total withdrawals 7 Withdrawals due to adverse events 8 Withdrawals due to treatment failure 9 Adverse events (local) 10 Adverse events (systemic)
No. of studies 0 1 0 0 1 2 2 2 1 2
No. of participants 0 318 0 0 318 1627 1627 1627 31 414
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size Not estimable -0.91 [-1.16, -0.67] Not estimable Not estimable -0.91 [-1.16, -0.67] 0.04 [-0.01, 0.09] 0.07 [0.05, 0.10] -0.02 [-0.04, 0.01] 0.24 [0.02, 0.46] Not estimable
274
Comparison 6. Other treatment vs. placebo
Outcome or subgroup title 1 IAGI 1.1 Aloe vera extract 1.2 Anti IL-8 monoclonal antibody cream 1.3 Betamethasone-17,21dipropionate plus salicylic acid 1.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 1.5 Ciclopirox olamine shampoo 1.6 Ciclosporin solution in oil 1.7 Dead Sea salts emollient lotion 1.8 Fish oil plus occlusion 1.9 Hexauoro-1,25dihydroxyvitamin D3 1.10 Methotrexate gel 1.11 Mycophenolic acid ointment 1.12 NG-monomethyl-Larginine (L-NMMA) cream 1.13 Oleum horwathiensis (Psoricur) 1.14 Omega-3polyunsaturated fatty acids ointment 1.15 Pimecrolimus cream, 1% BD 1.16 Platelet aggregation activating factor (PAF)(Ro 24-0238) 1.17 Polymyxin B cream, 200, 000U/g 1.18 PTH (1-34) in Novasome A liposomal cream, BD 1.19 Salicylic acid 1.20 Sirolimus (topical), 2. 2% for 6 wks, then 8% for a further 6 wks 1.21 Tacrolimus ointment 1.22 Tar 2 TSS 2.1 Aloe vera extract
No. of studies 9 0 1 1 1
No. of participants
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size Subtotals only Not estimable -0.59 [-1.01, -0.16] -1.68 [-2.73, -0.63] -0.76 [-1.21, -0.31]
0 89 20 81
0 0 0 0 1 1 0 0 1 0
0 0 0 0 30 80 0 0 42 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Not estimable Not estimable Not estimable Not estimable -0.62 [-1.35, 0.12] -0.56 [-1.01, -0.12] Not estimable Not estimable -0.02 [-0.63, 0.58] Not estimable
1 1
47 80
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
-1.07 [-1.69, -0.45] -0.07 [-0.50, 0.37]
0 0
0 0
1 0
20 0
-0.96 [-1.89, -0.02] Not estimable
0 1 16 0
0 36 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Not estimable -0.48 [-1.15, 0.18] Subtotals only Not estimable

275
2.2 Anti IL-8 monoclonal antibody cream 2.3 Betamethasone-17,21dipropionate plus salicylic acid 2.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 2.5 Ciclopirox olamine shampoo 2.6 Ciclosporin solution in oil 2.7 Dead Sea salts emollient lotion 2.8 Fish oil plus occlusion 2.9 Hexauoro-1,25dihydroxyvitamin D3, BD 2.10 Methotrexate gel 2.11 Mycophenolic acid ointment 2.12 NG-monomethyl-L-arginine (L-NMMA) cream 2.13 Oleum horwathiensis (Psoricur) 2.14 Omega-3polyunsaturated fatty acids ointment 2.15 Pimecrolimus cream, 1% BD 2.16 Platelet aggregation activating factor (PAF)(Ro 240238) 2.17 Polymyxin B cream, 200,000U/g 2.18 PTH (1-34) in Novasome A liposomal cream, BD 2.19 Salicylic acid 2.20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks 2.21 Tacrolimus ointment 2.22 Tar 3 PASI 3.1 Aloe vera extract 3.2 Anti IL-8 monoclonal antibody cream 3.3 Betamethasone-17,21dipropionate plus salicylic acid 3.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid
1 1 0
89 20 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
-0.70 [-1.13, -0.27] -0.95 [-1.89, -0.01] Not estimable
1 1 0 1 1 1 1 1
37 16 0 50 30 82 14 34
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
-0.07 [-0.82, 0.68] -1.24 [-2.33, -0.14] Not estimable -1.07 [-1.66, -0.47] -1.13 [-1.91, -0.35] -0.48 [-0.92, -0.04] -1.44 [-2.67, -0.22] 0.08 [-0.60, 0.75]
1 0
42 0
-0.77 [-1.40, -0.14] Not estimable
1 0
57 0
-1.28 [-1.86, -0.71] Not estimable
1 1
30 30
0.13 [-0.59, 0.85] -2.31 [-3.26, -1.36]
1 1
20 44
-0.59 [-1.49, 0.31] -0.39 [-0.98, 0.21]
1 1 4 1 0 0 1
47 36 60 0 0 81
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
0.06 [-0.51, 0.63] -0.45 [-1.11, 0.22] Subtotals only -1.62 [-2.21, -1.03] Not estimable Not estimable -0.54 [-0.99, -0.10]
276
3.5 Ciclopirox olamine shampoo 3.6 Ciclosporin solution in oil 3.7 Dead Sea salts emollient lotion, 30% 3.8 Fish oil plus occlusion 3.9 Hexauoro-1,25dihydroxyvitamin D3, BD 3.10 Methotrexate gel 3.11 Mycophenolic acid ointment 3.12 NG-monomethyl-Larginine (L-NMMA) cream 3.13 Oleum horwathiensis (Psoricur) 3.14 Omega-3polyunsaturated fatty acids ointment 3.15 Pimecrolimus cream, 1% BD 3.16 Platelet aggregation activating factor (PAF)(Ro 240238) 3.17 Polymyxin B cream, 200, 000U/g 3.18 PTH (1-34) in Novasome A liposomal cream, BD 3.19 Salicylic acid 3.20 Sirolimus (topical), 2. 2% for 6 wks, then 8% for a further 6 wks 3.21 Tacrolimus ointment 3.22 Tar 4 PAGI 4.1 Aloe vera extract 4.2 Anti IL-8 monoclonal antibody cream 4.3 Betamethasone-17,21dipropionate plus salicylic acid 4.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 4.5 Ciclopirox olamine shampoo 4.6 Ciclosporin solution in oil 4.7 Dead Sea salts emollient lotion, 30% 4.8 Fish oil plus occlusion 4.9 Hexauoro-1,25dihydroxyvitamin D3, BD
0 0 1 0 0 1 0 0 0 0
0 0 19 0 0 60 0 0 0 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Not estimable Not estimable 0.57 [-0.36, 1.51] Not estimable Not estimable -1.62 [-2.21, -1.03] Not estimable Not estimable Not estimable Not estimable
0 0
0 0
0 0
0 0
0 0
0 0
0 0 4 0 0 0 1
0 0 0 0 0 81
Not estimable Not estimable Subtotals only Not estimable Not estimable Not estimable -0.80 [-1.26, -0.35]
1 1 0 0 0
37 16 0 0 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
-0.11 [-0.86, 0.64] -3.94 [-5.79, -2.09] Not estimable Not estimable Not estimable
277
4.10 Methotrexate gel 4.11 Mycophenolic acid ointment 4.12 NG-monomethyl-Larginine (L-NMMA) cream 4.13 Oleum horwathiensis (Psoricur) 4.14 Omega-3polyunsaturated fatty acids ointment 4.15 Pimecrolimus cream, 1% BD 4.16 Platelet aggregation activating factor (PAF)(Ro 240238) 4.17 Polymyxin B cream, 200, 000U/g 4.18 PTH (1-34) in Novasome A liposomal cream, BD 4.19 Salicylic acid 4.20 Sirolimus (topical), 2. 2% for 6 wks, then 8% for a further 6 wks 4.21 Tacrolimus ointment 4.22 Tar 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Aloe vera extract 5.2 Anti IL-8 monoclonal antibody cream 5.3 Betamethasone-17,21dipropionate plus salicylic acid 5.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 5.5 Ciclopirox olamine shampoo 5.6 Ciclosporin solution in oil 5.7 Dead Sea salts emollient lotion, 30% 5.8 Fish oil plus occlusion 5.9 Hexauoro-1,25dihydroxyvitamin D3 5.10 Methotrexate gel 5.11 Mycophenolic acid ointment 5.12 NG-monomethyl-L-arginine (L-NMMA) cream
0 0 0 0 0
0 0 0 0 0
Not estimable Not estimable Not estimable Not estimable Not estimable
1 0
47 0
-0.65 [-1.24, -0.06] Not estimable
0 0
0 0
0 0
0 0
0 0 21 1 1 1 1
0 0
Not estimable Not estimable Subtotals only -1.62 [-2.21, -1.03] -0.59 [-1.01, -0.16] -1.68 [-2.73, -0.63] -0.76 [-1.21, -0.31]
60 89 20 81
1 1 1 1 1 2 1 1
37 16 19 50 30 140 14 34
-0.07 [-0.82, 0.68] -1.24 [-2.33, -0.14] 0.57 [-0.36, 1.51] -1.07 [-1.66, -0.47] -0.62 [-1.35, 0.12] -1.07 [-2.11, -0.04] -1.44 [-2.67, -0.22] 0.08 [-0.60, 0.75]
278
5.13 Oleum horwathiensis (Psoricur) 5.14 Omega-3polyunsaturated fatty acids ointment 5.15 Pimecrolimus cream, 1% BD 5.16 Platelet aggregation activating factor (PAF)(Ro 24-0238) 5.17 Polymyxin B cream, 200,000U/g 5.18 PTH (1-34) in Novasome A liposomal cream, BD 5.19 Salicylic acid 5.20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks 5.21 Tacrolimus ointment 5.22 Tar 6 Total withdrawals 6.1 Aloe vera extract 6.2 Anti IL-8 monoclonal antibody cream 6.3 Betamethasone-17,21dipropionate plus salicylic acid 6.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 6.5 Ciclopirox olamine shampoo 6.6 Ciclosporin solution in oil 6.7 Dead Sea salts emollient lotion 6.8 Fish oil plus occlusion 6.9 Hexauoro-1,25dihydroxyvitamin D3 6.10 Methotrexate gel 6.11 Mycophenolic acid ointment 6.12 NG-monomethyl-L-arginine (L-NMMA) cream 6.13 Oleum horwathiensis 6.14 Omega-3-polyunsaturated fatty acids ointment 6.15 Pimecrolimus cream, 1% BD
1 0
42 0
-0.02 [-0.63, 0.58] Not estimable
1 1
47 80
-1.07 [-1.69, -0.45] -0.07 [-0.50, 0.37]
1 1
30 30
0.13 [-0.59, 0.85] -2.31 [-3.26, -1.36]
1 1
20 44
-0.96 [-1.89, -0.02] -0.39 [-0.98, 0.21]
1 1 18 1 1 0 1
47 36 60 96 0 85
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.06 [-0.51, 0.63] -0.48 [-1.15, 0.18] Subtotals only Not estimable -0.02 [-0.12, 0.08] Not estimable -0.00 [-0.09, 0.09]
1 1 1 1 1 1 1 1
40 16 24 50 30 60 14 34
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.15 [-0.38, 0.09] Not estimable 0.25 [-0.06, 0.56] Not estimable Not estimable Not estimable Not estimable Not estimable
1 1
50 146
0.16 [-0.04, 0.36] Not estimable
57
-0.07 [-0.22, 0.09]
279
6.16 Platelet aggregation activating factor (PAF)(Ro 24-0238) 6.17 Polymyxin B cream, 200,000U/g 6.18 PTH (1-34) in Novasome A liposomal cream, BD 6.19 Salicylic acid 6.20 Sirolimus (topical) 6.21 Tacrolimus ointment 6.22 Tar 7 Withdrawals due to adverse events 7.1 Aloe vera extract 7.2 Anti IL-8 monoclonal antibody cream 7.3 Betamethasone-17,21dipropionate plus salicylic acid 7.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 7.5 Ciclopirox olamine shampoo 7.6 Ciclosporin solution in oil 7.7 Dead Sea salts emollient lotion 7.8 Fish oil plus occlusion 7.9 Hexauoro-1,25dihydroxyvitamin D3 7.10 Methotrexate gel 7.11 Mycophenolic acid ointment 7.12 NG-monomethyl-L-arginine (L-NMMA) cream 7.13 Oleum horwathiensis 7.14 Omega-3-polyunsaturated fatty acids ointment 7.15 Pimecrolimus cream, 1% BD 7.16 Platelet aggregation activating factor (PAF)(Ro 240238) 7.17 Polymyxin B cream, 200, 000U/g 7.18 PTH (1-34) in Novasome A liposomal cream, BD 7.19 Salicylic acid
104
Not estimable
1 1
30 30
0 0 1 0 16 1 0 1 1
0 0 167 0
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable -0.17 [-0.30, -0.03] Not estimable Subtotals only Not estimable Not estimable Not estimable -0.00 [-0.07, 0.06]
60 0 20 85
1 1 1 1 1 1 1 1
40 16 24 50 30 60 14 34
1 1
50 146
1 0
57 0
0 1
0 30
20
Not estimable
280
7.20 Sirolimus (topical) 7.21 Tacrolimus ointment 7.22 Tar 8 Withdrawals due to treatment failure 8.1 Aloe vera extract 8.2 Anti IL-8 monoclonal antibody cream 8.3 Betamethasone-17,21dipropionate plus salicylic acid 8.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 8.5 Ciclopirox olamine shampoo 8.6 Ciclosporin solution in oil 8.7 Dead Sea salts emollient lotion 8.8 Fish oil plus occlusion 8.9 Hexauoro-1,25dihydroxyvitamin D3 8.10 Methotrexate gel 8.11 Mycophenolic acid ointment 8.12 NG-monomethyl-L-arginine (L-NMMA) cream 8.13 Oleum horwathiensis 8.14 Omega-3-polyunsaturated fatty acids ointment 8.15 Pimecrolimus cream, 1% BD 8.16 Platelet aggregation activating factor (PAF)(Ro 240238) 8.17 Polymyxin B cream, 200, 000U/g 8.18 PTH (1-34) in Novasome A liposomal cream, BD 8.19 Salicylic acid 8.20 Sirolimus (topical) 8.21 Tacrolimus ointment 8.22 Tar 9 Adverse events (local) 9.1 Aloe vera extract 9.2 Anti IL-8 monoclonal antibody cream 9.3 Betamethasone-17,21dipropionate plus salicylic acid
0 1 0 15 1 0 0 1
0 167 0
Not estimable -0.02 [-0.06, 0.03] Not estimable Subtotals only Not estimable Not estimable Not estimable 0.02 [-0.04, 0.08]
60 0 0 85
1 1 1 1 1 1 1 1
40 16 24 50 30 60 14 34
1 1
50 146
1 0
57 0
-0.03 [-0.15, 0.08] Not estimable
0 1
0 30
0 0 1 0 18 1 1 1
0 0 167 0 60 92 20
Not estimable Not estimable -0.11 [-0.19, -0.02] Not estimable Subtotals only Not estimable 0.02 [-0.10, 0.14] Not estimable
281
9.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 9.5 Ciclopirox olamine shampoo 9.6 Ciclosporin solution in oil 9.7 Dead Sea salts emollient lotion 9.8 Fish oil plus occlusion 9.9 Hexauoro-1,25dihydroxyvitamin D3 9.10 Methotrexate gel 9.11 Mycophenolic acid ointment 9.12 NG-monomethyl-L-arginine (L-NMMA) cream 9.13 Oleum horwathiensis 9.14 Omega-3-polyunsaturated fatty acids ointment 9.15 Pimecrolimus cream, 1% BD 9.16 Platelet aggregation activating factor (PAF)(Ro 24-0238) 9.17 Polymyxin B cream, 200, 000U/g 9.18 PTH (1-34) in Novasome A liposomal cream, BD 9.19 Salicylic acid 9.20 Sirolimus (topical) 9.21 Tacrolimus ointment 9.22 Tar 10 Adverse events (systemic) 10.1 Aloe vera extract 10.2 Anti IL-8 monoclonal antibody cream 10.3 Betamethasone-17,21dipropionate plus salicylic acid 10.4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 10.5 Ciclopirox olamine shampoo 10.6 Ciclosporin solution in oil 10.7 Dead Sea salts emollient lotion 10.8 Fish oil plus occlusion
85
-0.00 [-0.07, 0.06]
1 1 1 1 1 1 1 1
40 16 24 50 30 60 14 34
-0.06 [-0.24, 0.13] Not estimable 0.08 [-0.18, 0.35] 0.04 [-0.06, 0.14] 0.13 [-0.06, 0.33] Not estimable Not estimable Not estimable
1 1
50 146
0.04 [-0.06, 0.14] 0.01 [-0.02, 0.05]
1 1
57 104
0.00 [-0.09, 0.10] Not estimable
0 1
0 30
1 0 1 0 10 0 0 0 1
20 0 167 0 0 0 0 85
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable -0.17 [-0.30, -0.03] Not estimable Subtotals only Not estimable Not estimable Not estimable Not estimable
0 1 0 0
0 16 0 0
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable Not estimable Not estimable

282
10.9 Hexauoro-1,25dihydroxyvitamin D3 10.10 Methotrexate gel 10.11 Mycophenolic acid ointment 10.12 NG-monomethyl-L-arginine (L-NMMA) cream 10.13 Oleum horwathiensis 10.14 Omega-3polyunsaturated fatty acids ointment 10.15 Pimecrolimus cream, 1% BD 10.16 Platelet aggregation activating factor (PAF)(Ro 24-0238) 10.17 Polymyxin B cream, 200,000U/g 10.18 PTH (1-34) in Novasome A liposomal cream, BD 10.19 Salicylic acid 10.20 Sirolimus (topical) 10.21 Tacrolimus ointment 10.22 Tar
1 2 0 1
30 166 0 34
1 0
50 0
0 1
0 104
0 1
0 30
0 0 1 0
0 0 167 0
Comparison 7. Vitamin D analogues vs. corticosteroid (potent)
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. betamethasone dipropionate 1.2 Calcipotriol vs. betamethasone valerate 1.3 Calcipotriol vs. desoxymetasone 1.4 Calcipotriol vs. diorasone diacetate 1.5 Calcipotriol vs. uocinonide 1.6 Calcitriol vs. betamethasone dipropionate 1.7 Calcitriol vs. betamethasone valerate 1.8 Tacalcitol vs. betamethasone valerate
No. of studies 8 1 3 0 1 1 1 1 0
No. of participants 2185 620 922 0 256 99 258 30 0
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size 0.07 [-0.11, 0.26] Not estimable 0.19 [-0.13, 0.52] Not estimable 0.27 [0.02, 0.52] -0.58 [-0.99, -0.18] 0.21 [-0.04, 0.45] -0.19 [-0.91, 0.53] Not estimable
283
2 TSS 2.1 Calcipotriol vs. betamethasone dipropionate 2.2 Calcipotriol vs. betamethasone valerate 2.3 Calcipotriol vs. desoxymetasone 2.4 Calcipotriol vs. diorasone diacetate 2.5 Calcipotriol vs. uocinonide 2.6 Calcitriol vs. betamethasone dipropionate 2.7 Calcitriol vs. betamethasone valerate 2.8 Tacalcitol vs. betamethasone valerate 3 PASI 3.1 Calcipotriol vs. betamethasone dipropionate 3.2 Calcipotriol vs. betamethasone valerate 3.3 Calcipotriol vs. desoxymetasone 3.4 Calcipotriol vs. diorasone diacetate 3.5 Calcipotriol vs. uocinonide 3.6 Calcitriol vs. betamethasone dipropionate 3.7 Calcitriol vs. betamethasone valerate 3.8 Tacalcitol vs. betamethasone valerate 4 PAGI 4.1 Calcipotriol vs. betamethasone dipropionate 4.2 Calcipotriol vs. betamethasone valerate 4.3 Calcipotriol vs. desoxymetasone 4.4 Calcipotriol vs. diorasone diacetate 4.5 Calcipotriol vs. uocinonide 4.6 Calcitriol vs. betamethasone dipropionate 4.7 Calcitriol vs. betamethasone valerate
9 1 3 0 1 1 1 0 2 8 2 4 1 0 0 1 0 0 3 0 3 0 0 0 0 0
2878 956 1171 0 256 89 258 0 148 3359 1576 1505 20 0 0 258 0 0 1548 0 1548 0 0 0 0 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
0.14 [-0.08, 0.37] 0.37 [0.24, 0.50] -0.06 [-0.34, 0.23] Not estimable 0.40 [0.15, 0.64] -0.49 [-0.91, -0.06] 0.26 [0.02, 0.51] Not estimable 0.41 [0.08, 0.74] 0.12 [-0.09, 0.34] 0.41 [0.30, 0.51] -0.12 [-0.22, -0.02] 0.15 [-0.73, 1.02] Not estimable Not estimable 0.39 [0.14, 0.63] Not estimable Not estimable -0.04 [-0.46, 0.39] Not estimable -0.04 [-0.46, 0.39] Not estimable Not estimable Not estimable Not estimable Not estimable
284
4.8 Tacalcitol vs. betamethasone valerate 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. betamethasone dipropionate 5.2 Calcipotriol vs. betamethasone valerate 5.3 Calcipotriol vs. desoxymetasone 5.4 Calcipotriol vs. diorasone diacetate 5.5 Calcipotriol vs. uocinonide 5.6 Calcitriol vs. betamethasone dipropionate 5.7 Calcitriol vs. betamethasone valerate 5.8 Tacalcitol vs. betamethasone valerate 6 Total withdrawals 6.1 Calcipotriol vs. betamethasone dipropionate 6.2 Calcipotriol vs. betamethasone valerate 6.3 Calcipotriol vs. desoxymetasone 6.4 Calcipotriol vs. diorasone diacetate 6.5 Calcipotriol vs. uocinonide 6.6 Calcitriol vs. betamethasone dipropionate 6.7 Calcitriol vs. betamethasone valerate 6.8 Tacalcitol vs. betamethasone valerate 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. betamethasone dipropionate 7.2 Calcipotriol vs. betamethasone valerate 7.3 Calcipotriol vs. desoxymetasone 7.4 Calcipotriol vs. diorasone diacetate 7.5 Calcipotriol vs. uocinonide 7.6 Calcitriol vs. betamethasone dipropionate
0 15 2 6 1 1 1 1 1 2 12 2 5 0 1 0 1 1 2 11 1 5 0 0 1 1
0 4454 1576 2067 20 256 99 258 30 148 4349 1577 2036 0 268 0 258 30 180 3574 956 2036 0 0 114 258
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable 0.08 [-0.07, 0.24] 0.19 [-0.17, 0.55] 0.02 [-0.22, 0.25] 0.15 [-0.73, 1.02] 0.27 [0.02, 0.52] -0.58 [-0.99, -0.18] 0.21 [-0.04, 0.45] -0.19 [-0.91, 0.53] 0.41 [0.08, 0.74] 0.02 [0.01, 0.03] 0.03 [0.01, 0.06] Not estimable Not estimable Not estimable Not estimable -0.02 [-0.08, 0.03] 0.07 [-0.10, 0.23] Not estimable 0.01 [0.00, 0.02] 0.02 [0.00, 0.04] 0.01 [-0.00, 0.03] Not estimable Not estimable -0.02 [-0.06, 0.03] 0.01 [-0.02, 0.03]
285
7.7 Calcitriol vs. betamethasone valerate 7.8 Tacalcitol vs. betamethasone valerate 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. betamethasone dipropionate 8.2 Calcipotriol vs. betamethasone valerate 8.3 Calcipotriol vs. desoxymetasone 8.4 Calcipotriol vs. diorasone diacetate 8.5 Calcipotriol vs. uocinonide 8.6 Calcitriol vs. betamethasone dipropionate 8.7 Calcitriol vs. betamethasone valerate 8.8 Tacalcitol vs. betamethasone valerate 9 Adverse events (local) 9.1 Calcipotriol vs. betamethasone dipropionate 9.2 Calcipotriol vs. betamethasone valerate 9.3 Calcipotriol vs. desoxymetasone 9.4 Calcipotriol vs. diorasone diacetate 9.5 Calcipotriol vs. uocinonide 9.6 Calcitriol vs. betamethasone dipropionate 9.7 Calcitriol vs. betamethasone valerate 9.8 Tacalcitol vs. betamethasone valerate 10 Adverse events (systemic) 10.1 Calcipotriol vs. betamethasone dipropionate 10.2 Calcipotriol vs. betamethasone valerate 10.3 Calcipotriol vs. desoxymetasone 10.4 Calcipotriol vs. diorasone diacetate 10.5 Calcipotriol vs. uocinonide
1 2 7 0 4 0 0 1 1 1 0 10 2 5 0 0 1 1 0 1 7 1 4 0 0 0
30 180 2016 0 1615 0 0 113 258 30 0 4132 1577 2032 0 0 113 258 0 152 3021 621 1990 0 0 0
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.07 [-0.10, 0.23] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable 0.01 [-0.03, 0.05] Not estimable Not estimable 0.09 [0.04, 0.14] 0.07 [0.04, 0.10] 0.14 [0.03, 0.25] Not estimable Not estimable 0.10 [-0.02, 0.22] Not estimable Not estimable -0.01 [-0.07, 0.04] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable
286
10.6 Calcitriol vs. betamethasone dipropionate 10.7 Calcitriol vs. betamethasone valerate 10.8 Tacalcitol vs. betamethasone valerate
1 0 1
258 0 152
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.01 [-0.04, 0.03] Not estimable Not estimable
Comparison 8. Vitamin D analogues vs. corticosteroid (very potent)
Outcome or subgroup title 1 IAGI 2 TSS 2.1 Calcipotriol vs. Clobetasol propionate 3 PASI 3.1 Calcipotriol vs. Clobetasol propionate 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. Clobetasol propionate 6 Total withdrawals 6.1 Calcipotriol vs. Clobetasol propionate 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. Clobetasol propionate 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. Clobetasol propionate 9 Adverse events (local) 9.1 Calcipotriol vs. Clobetasol propionate 10 Adverse events (systemic) 10.1 Calcipotriol vs. Clobetasol propionate
No. of studies 0 1 1 1 1 0 2 2 1 1 1 1 1 1 3 3 1 1
No. of participants 0 151 151 40 40 0 191 191 43 43 43 43 43 43 234 234 40 40
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size Not estimable 0.37 [0.05, 0.69] 0.37 [0.05, 0.69] -0.32 [-0.95, 0.30] -0.32 [-0.95, 0.30] Not estimable 0.08 [-0.60, 0.75] 0.08 [-0.60, 0.75] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable 0.09 [-0.10, 0.28] 0.09 [-0.10, 0.28] -0.05 [-0.18, 0.08] -0.05 [-0.18, 0.08]
287
Comparison 9. Vitamin D analogues-potent steroid combination vs. potent corticosteroid
Outcome or subgroup title 1 IAGI 1.1 Dovobet vs. betamethasone dipropionate 2 TSS 2.1 Dovobet vs. betamethasone dipropionate 3 PASI 3.1 Dovobet vs. betamethasone dipropionate 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Dovobet vs. betamethasone dipropionate 6 Total withdrawals 6.1 Dovobet vs. betamethasone dipropionate 7 Withdrawals due to adverse events 7.1 Dovobet vs. betamethasone dipropionate 8 Withdrawals due to treatment failure 9 Adverse events (local) 9.1 Dovobet vs. betamethasone dipropionate 10 Adverse events (systemic) 10.1 Dovobet vs. betamethasone dipropionate
No. of studies 1 1 1 1 2 2 0 2 2 2 2 1 1 0 2 2 1 1
No. of participants 732 732 966 966 1651 1651 0 1698 1698 1703 1703 966 966 0 1703 1703 737 737
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size -0.46 [-0.60, -0.31] -0.46 [-0.60, -0.31] -0.43 [-0.56, -0.31] -0.43 [-0.56, -0.31] -0.48 [-0.58, -0.38] -0.48 [-0.58, -0.38] Not estimable -0.44 [-0.54, -0.35] -0.44 [-0.54, -0.35] -0.00 [-0.04, 0.03] -0.00 [-0.04, 0.03] -0.00 [-0.02, 0.01] -0.00 [-0.02, 0.01] Not estimable 0.02 [-0.00, 0.04] 0.02 [-0.00, 0.04] Not estimable Not estimable
Comparison 10. Vitamin D analogues vs. dithranol
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. dithranol 1.2 Tacalcitol vs. dithranol 1.3 Calcitriol vs. dithranol 2 TSS 2.1 Calcipotriol vs. dithranol 2.2 Tacalcitol vs. dithranol 2.3 Calcitriol vs. dithranol
No. of studies 4 3 0 1 4 2 1 1
No. of participants 1022 908 0 114 408 210 84 114
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size -0.40 [-0.87, 0.07] -0.69 [-0.86, -0.51] Not estimable 0.51 [0.13, 0.88] -0.27 [-0.73, 0.19] -0.54 [-1.14, 0.07] -0.18 [-0.60, 0.25] 0.13 [-0.24, 0.50]
288
3 PASI 3.1 Calcipotriol vs. dithranol 3.2 Tacalcitol vs. dithranol 3.3 Calcitriol vs. dithranol 4 PAGI 4.1 Calcipotriol vs. dithranol 4.2 Tacalcitol vs. dithranol 4.3 Calcitriol vs. dithranol 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. dithranol 5.2 Tacalcitol vs. dithranol 5.3 Calcitriol vs. dithranol 6 Total withdrawals 6.1 Calcipotriol vs. dithranol 6.2 Tacalcitol vs. dithranol 6.3 Calcitriol vs. dithranol 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. dithranol 7.2 Tacalcitol vs. dithranol 7.3 Calcitriol vs. dithranol 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. dithranol 8.2 Tacalcitol vs. dithranol 8.3 Calcitriol vs. dithranol 9 Adverse events (local) 9.1 Calcipotriol vs. dithranol 9.2 Tacalcitol vs. dithranol 9.3 Calcitriol vs. dithranol 10 Adverse events (systemic) 10.1 Calcipotriol vs. dithranol 10.2 Tacalcitol vs. dithranol 10.3 Calcitriol vs. dithranol
4 2 1 1 1 1 0 0 7 5 1 1 6 4 1 1 6 5 0 1 4 3 0 1 8 6 1 1 4 2 1 1
690 492 84 114 458 458 0 0 1220 1022 84 114 509 311 84 114 1159 1045 0 114 682 568 0 114 1438 1240 84 114 746 548 84 114
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.41 [-0.47, 1.29] 1.02 [-1.71, 3.76] -0.07 [-0.50, 0.36] -0.19 [-0.56, 0.18] -0.47 [-0.65, -0.28] -0.47 [-0.65, -0.28] Not estimable Not estimable 0.04 [-0.53, 0.61] -0.01 [-0.71, 0.69] -0.18 [-0.60, 0.25] 0.51 [0.13, 0.88] -0.03 [-0.06, 0.00] -0.03 [-0.06, 0.01] -0.02 [-0.16, 0.11] -0.10 [-0.25, 0.06] -0.04 [-0.06, -0.01] -0.04 [-0.06, -0.01] Not estimable -0.06 [-0.13, 0.02] -0.00 [-0.02, 0.02] Not estimable Not estimable -0.02 [-0.08, 0.04] -0.28 [-0.45, -0.11] -0.20 [-0.36, -0.04] -0.36 [-0.52, -0.20] -0.67 [-0.80, -0.54] -0.00 [-0.01, 0.01] -0.00 [-0.02, 0.01] Not estimable Not estimable
Comparison 11. Vitamin D analogues vs. coal tar
Outcome or subgroup title 1 IAGI 1.1 calcipotriol vs. coal tar 1.2 calcipotriol vs. white soft parafn + coal tar 2 TSS 3 PASI 3.1 calcipotriol vs. coal tar
No. of studies 2 1 1 0 1 0
No. of participants 84 30 54 0 54 0
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size -1.13 [-1.60, -0.67] -1.01 [-1.77, -0.24] -1.21 [-1.79, -0.62] Not estimable -0.84 [-1.39, -0.28] Not estimable
289
3.2 calcipotriol vs. white soft parafn + coal tar 4 PAGI 4.1 calcipotriol vs. coal tar 4.2 calcipotriol vs. white soft parafn + coal tar 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 calcipotriol vs. coal tar 5.2 calcipotriol vs. white soft parafn + coal tar 6 Total withdrawals 6.1 calcipotriol vs. coal tar 6.2 calcipotriol vs. white soft parafn + coal tar 7 Withdrawals due to adverse events 7.1 calcipotriol vs. coal tar 7.2 calcipotriol vs. white soft parafn + coal tar 8 Withdrawals due to treatment failure 8.1 calcipotriol vs. coal tar 8.2 calcipotriol vs. white soft parafn + coal tar 9 Adverse events (local) 10 Adverse events (systemic) 10.1 calcipotriol vs. coal tar 10.2 calcipotriol vs. white soft parafn + coal tar
1 1 0 1 2 1 1 1 0 1 1 0 1 1 0 1 0 1 0 1
54 54 0 54 84 30 54 60 0 60 60 0 60 60 0 60 0 60 0 60
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.84 [-1.39, -0.28] -1.51 [-2.12, -0.90] Not estimable -1.51 [-2.12, -0.90] -1.13 [-1.60, -0.67] -1.01 [-1.77, -0.24] -1.21 [-1.79, -0.62] Not estimable Not estimable Not estimable 0.03 [-0.05, 0.12] Not estimable 0.03 [-0.05, 0.12] Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable Not estimable
Comparison 12. Vitamin D analogue vs. vitamin D analogue
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. calcitriol 1.2 Calcipotriol vs. tacalcitol 1.3 Calcipotriol vs. maxacalcitol 2 TSS 2.1 Calcipotriol vs. calcitriol 2.2 Calcipotriol vs. tacalcitol 2.3 Calcipotriol vs. maxacalcitol 3 PASI 3.1 Calcipotriol vs. calcitriol 3.2 Calcipotriol vs. tacalcitol
No. of studies 2 0 1 1 3 1 1 1 1 1 0
No. of participants 278 0 226 52 489 150 287 52 15 15 0
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size -0.06 [-0.93, 0.82] Not estimable -0.47 [-0.73, -0.21] 0.43 [-0.12, 0.98] 0.09 [-0.65, 0.82] 0.61 [0.28, 0.93] -0.45 [-0.68, -0.22] 0.13 [-0.41, 0.68] -1.11 [-2.22, 0.01] -1.11 [-2.22, 0.01] Not estimable
290
3.3 Calcipotriol vs. maxacalcitol 4 PAGI 4.1 Calcipotriol vs. calcitriol 4.2 Calcipotriol vs. tacalcitol 4.3 Calcipotriol vs. maxacalcitol 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. calcitriol 5.2 Calcipotriol vs. tacalcitol 5.3 Calcipotriol vs. maxacalcitol 6 Total withdrawals 6.1 Calcipotriol vs. calcitriol 6.2 Calcipotriol vs. tacalcitol 6.3 Calcipotriol vs. maxacalcitol 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. calcitriol 7.2 Calcipotriol vs. tacalcitol 7.3 Calcipotriol vs. maxacalcitol 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. calcitriol 8.2 Calcipotriol vs. tacalcitol 8.3 Calcipotriol vs. maxacalcitol 9 Adverse events (local) 9.1 Calcipotriol vs. calcitriol 9.2 Calcipotriol vs. tacalcitol 9.3 Calcipotriol vs. maxacalcitol 10 Adverse events (systemic) 10.1 Calcipotriol vs. calcitriol 10.2 Calcipotriol vs. tacalcitol 10.3 Calcipotriol vs. maxacalcitol
0 0 0 0 0 4 2 1 1 3 2 0 1 3 2 0 1 3 2 0 1 2 1 1 0 2 0 1 1
0 0 0 0 0 443 165 226 52 234 174 0 60 234 174 0 60 234 174 0 60 437 150 287 0 347 0 287 60
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable Not estimable Not estimable Not estimable -0.05 [-0.76, 0.67] -0.16 [-1.83, 1.51] -0.47 [-0.73, -0.21] 0.43 [-0.12, 0.98] Not estimable Not estimable Not estimable Not estimable 0.03 [-0.05, 0.11] 0.07 [-0.02, 0.15] Not estimable Not estimable Not estimable -0.00 [-0.05, 0.05] Not estimable Not estimable 0.04 [-0.06, 0.15] 0.09 [0.02, 0.17] -0.01 [-0.09, 0.07] Not estimable Not estimable Not estimable Not estimable Not estimable
291
Comparison 13. Vitamin D analogue vs. vitamin D and corticosteroid
Outcome or subgroup title 1 IAGI 1.1 calcipotriol vs. calcipotriol then cal. OM, BMV ON 1.2 calcipotriol vs. clobetasol propionate then calcipotriol 1.3 calcipotriol vs. calcipotriol OM, BMD ON 1.4 calcipotriol vs. calcipotriol OM, BMV ON 1.5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON 1.6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON 1.7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON 1.8 calcipotriol vs. Dovobet BD 1.9 calcipotriol vs. Dovobet ON (placebo OM) 1.10 calcipotriol vs. Dovobet OD 1.11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) 2 TSS 2.1 calcipotriol vs. calcipotriol then cal. OM, BMV ON 2.2 calcipotriol vs. clobetasol propionate then calcipotriol 2.3 calcipotriol vs. calcipotriol OM, BMD ON 2.4 calcipotriol vs. calcipotriol OM, BMV ON 2.5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON 2.6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON 2.7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON 2.8 calcipotriol vs. Dovobet BD
No. of studies 7 1 1 1 1 1 0
No. of participants 3281 164 92 154 346 344 0
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size 0.46 [0.27, 0.66] 0.53 [0.22, 0.84] 0.60 [0.18, 1.02] 0.56 [0.23, 0.88] 0.26 [0.05, 0.47] Not estimable Not estimable
Std. Mean Difference (IV, Random, 95% CI)
Not estimable
3 1 0 0
1804 377 0 0
0.66 [0.40, 0.93] 0.27 [0.06, 0.48] Not estimable Not estimable
2 0 1 0 0 0 0
1062 0 92 0 0 0 0
0.80 [0.68, 0.93] Not estimable 0.63 [0.21, 1.05] Not estimable Not estimable Not estimable Not estimable
Not estimable
Not estimable
292
2.9 calcipotriol vs. Dovobet ON (placebo OM) 2.10 calcipotriol vs. Dovobet OD 2.11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) 3 PASI 3.1 calcipotriol vs. calcipotriol then cal. OM, BMV ON 3.2 calcipotriol vs. clobetasol propionate then calcipotriol 3.3 calcipotriol vs. calcipotriol OM, BMD ON 3.4 calcipotriol vs. calcipotriol OM, BMV ON 3.5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON 3.6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON 3.7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON 3.8 calcipotriol vs. Dovobet BD 3.9 calcipotriol vs. Dovobet ON (placebo OM) 3.10 calcipotriol vs. Dovobet OD 3.11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 calcipotriol vs. calcipotriol then cal. OM, BMV ON 5.2 calcipotriol vs. clobetasol propionate then calcipotriol 5.3 calcipotriol vs. calcipotriol OM, BMD ON 5.4 calcipotriol vs. calcipotriol OM, BMV ON 5.5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON 5.6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON
0 1 0
0 970 0
Not estimable 0.82 [0.69, 0.95] Not estimable
11 1 0 1 1 1 1
5322 169 0 156 346 344 116
0.52 [0.38, 0.66] 0.70 [0.39, 1.01] Not estimable 0.46 [0.14, 0.78] 0.19 [-0.02, 0.40] 0.17 [-0.04, 0.38] 0.08 [-0.29, 0.44]
38
0.53 [-0.11, 1.18]
3 1 2 1
1744 377 1619 413
0.64 [0.46, 0.83] 0.40 [0.19, 0.61] 0.69 [0.34, 1.05] 0.78 [0.58, 0.98]
0 12 1 1 1 1 1 1
0 5467 164 92 154 346 344 116
Not estimable 0.50 [0.35, 0.65] 0.53 [0.22, 0.84] 0.60 [0.18, 1.02] 0.56 [0.23, 0.88] 0.26 [0.05, 0.47] Not estimable 0.08 [-0.29, 0.44]
293
5.7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON 5.8 calcipotriol vs. Dovobet BD 5.9 calcipotriol vs. Dovobet ON (placebo OM) 5.10 calcipotriol vs. Dovobet OD 5.11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) 6 Total withdrawals 6.1 Calcipotriol vs. calcipotriol and corticosteroid 6.2 Tacalcitol vs. calcipotriol and corticosteroid 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. calcipotriol and corticosteroid 7.2 Tacalcitol vs. calcipotriol and corticosteroid 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. calcipotriol and corticosteroid 8.2 Tacalcitol vs. calcipotriol and corticosteroid 9 Adverse events (local) 9.1 Calcipotriol vs. calcipotriol and corticosteroid 9.2 Tacalcitol vs. calcipotriol and corticosteroid 10 Adverse events (systemic) 10.1 Calcipotriol vs. calcipotriol and corticosteroid 10.2 Tacalcitol vs. calcipotriol and corticosteroid
38
0.53 [-0.11, 1.18]
3 1 2 1
1804 377 1619 413
0.66 [0.40, 0.93] 0.27 [0.06, 0.48] 0.67 [0.36, 0.97] 0.78 [0.58, 0.98]
11 10 1 9 8 1 6 5 1 12 11 1 4 4 0
5049 4548 501 3228 2727 501 1901 1400 501 5219 4718 501 1648 1648 0
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.04 [0.02, 0.05] 0.04 [0.02, 0.05] 0.05 [-0.01, 0.12] 0.02 [0.01, 0.03] 0.02 [0.01, 0.03] 0.02 [-0.01, 0.05] 0.01 [-0.00, 0.03] 0.01 [-0.00, 0.02] 0.05 [0.02, 0.08] 0.07 [0.05, 0.09] 0.07 [0.04, 0.09] 0.06 [0.01, 0.11] Not estimable Not estimable Not estimable
Comparison 14. Calcipotriol vs. corticosteroid and salicylic acid
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid
No. of studies 1 1
Effect size -0.06 [-0.33, 0.22] -0.06 [-0.33, 0.22]
294
2 TSS 3 PASI 3.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 4 PAGI 4.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 6 Total withdrawals 6.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 9 Adverse events (local) 9.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid 10 Adverse events (systemic) 10.1 Calcipotriol vs. betamethasone dipropionate + salicylic acid
0 1 1
0 160 160
Not estimable -0.05 [-0.36, 0.26] -0.05 [-0.36, 0.26]
1 1
186 186
-0.49 [-0.79, -0.20] -0.49 [-0.79, -0.20]
2 2
360 360
-0.05 [-0.26, 0.15] -0.05 [-0.26, 0.15]
2 2
218 218
0.01 [-0.10, 0.12] 0.01 [-0.10, 0.12]
1 1
160 160
0.05 [-0.00, 0.10] 0.05 [-0.00, 0.10]
1 1
160 160
-0.02 [-0.07, 0.02] -0.02 [-0.07, 0.02]
2 2
218 218
1 1
160 160
Comparison 15. Calcipotriol vs. coal tar polytherapy
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal )
No. of studies 3 1
Effect size -0.52 [-0.68, -0.36] -0.49 [-0.68, -0.29]
295
1.2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream 1.3 Calcipotriol vs. dithranol / tar regimen 2 TSS 2.1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ) 2.2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream 2.3 Calcipotriol vs. dithranol / tar regimen 3 PASI 3.1 Calcipotriol vs. coal tar, 1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ) 3.2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream 3.3 Calcipotriol vs. dithranol / tar regimen 4 PAGI 4.1 Calcipotriol vs. coal tar, 1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ) 4.2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream 4.3 Calcipotriol vs. dithranol / tar regimen 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ) 5.2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream 5.3 Calcipotriol vs. dithranol / tar regimen 6 Total withdrawals 6.1 Calcipotriol vs. coal tar polytherapy (any) 7 Withdrawals due to adverse events
122
-0.47 [-0.83, -0.11]
1 3 1
87 639 420
-0.75 [-1.19, -0.32] -0.54 [-0.90, -0.18] -0.28 [-0.48, -0.09]
132
-0.50 [-0.85, -0.15]
1 1 0
87 87 0
-0.95 [-1.40, -0.51] -0.64 [-1.07, -0.21] Not estimable
Not estimable
1 1 0
87 87 0
-0.64 [-1.07, -0.21] -0.56 [-0.99, -0.13] Not estimable
Not estimable
1 3 1
87 626 417
-0.56 [-0.99, -0.13] -0.52 [-0.68, -0.36] -0.49 [-0.68, -0.29]
122
-0.47 [-0.83, -0.11]
1 3 3 3
87 695 695 655
Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
-0.75 [-1.19, -0.32] -0.01 [-0.06, 0.04] -0.01 [-0.06, 0.04] 0.02 [-0.06, 0.10]
296
7.1 Calcipotriol vs. coal tar polytherapy (any) 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. coal tar polytherapy (any) 9 Adverse events (local) 9.1 Calcipotriol vs. coal tar polytherapy (any) 10 Adverse events (systemic) 10.1 Calcipotriol vs. coal tar polytherapy (any)
3 1 1 2 2 2 2
655 88 88 567 567 533 533
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.02 [-0.06, 0.10] 0.00 [-0.06, 0.07] 0.00 [-0.06, 0.07] 0.15 [-0.03, 0.33] 0.15 [-0.03, 0.33] Not estimable Not estimable
Comparison 16. Head-to-head calcipotriol: Dosing
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol BD vs. calcipotriol OD 1.2 Calcipotriol BD vs. calcipotriol OM, vehicle ON 2 TSS 3 PASI 3.1 Calcipotriol BD vs. calcipotriol OD 3.2 Calcipotriol BD vs. calcipotriol OM, vehicle ON 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol BD vs. calcipotriol OD 5.2 Calcipotriol BD vs. calcipotriol OM, vehicle ON 6 Total withdrawals 7 Withdrawals due to adverse events 8 Withdrawals due to treatment failure 9 Adverse events (local) 10 Adverse events (systemic)
No. of studies 1 0 1 0 2 1 1 0 2 1 1 2 2 2 1 1
No. of participants 344 0 344 0 605 260 345 0 604 260 344 612 612 612 345 264
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Effect size -0.27 [-0.48, -0.06] Not estimable -0.27 [-0.48, -0.06] Not estimable -0.12 [-0.28, 0.03] -0.10 [-0.34, 0.15] -0.15 [-0.36, 0.06] Not estimable -0.19 [-0.37, -0.02] -0.10 [-0.34, 0.15] -0.27 [-0.48, -0.06] 0.01 [-0.05, 0.06] 0.01 [-0.02, 0.04] Not estimable -0.03 [-0.13, 0.07] Not estimable
297
Comparison 17. Head-to-head calcipotriol: Occlusion
Outcome or subgroup title 1 IAGI 2 TSS 2.1 Calcipotriol BD vs. calcipotriol BD + occlusion ON 3 PASI 4 PAGI 5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol BD vs. calcipotriol BD + occlusion ON 6 Total withdrawals 7 Withdrawals due to adverse events 8 Withdrawals due to treatment failure 9 Adverse events (local) 10 Adverse events (systemic)
No. of studies 0 1 1
No. of participants 0 38 38
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size Not estimable 0.79 [0.13, 1.45] 0.79 [0.13, 1.45]
0 0 1 1
0 0 38 38
Not estimable Not estimable 0.79 [0.13, 1.45] 0.79 [0.13, 1.45]
0 0 0 0 1
0 0 0 0 38
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
Not estimable Not estimable Not estimable Not estimable Not estimable
Comparison 18. Vitamin D analogues vs. other treatment
Outcome or subgroup title 1 IAGI 1.1 Calcipotriol vs. propylthiouracil cream 1.2 Calcipotriol vs. tacrolimus ointment 1.3 Calcipotriol vs. tazarotene 1.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 1.5 Calcipotriol vs. vitamin B12 cream 1.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 1.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 2 TSS
No. of studies 1 0 0 0 0
No. of participants
Statistical method Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Effect size Subtotals only Not estimable Not estimable Not estimable Not estimable
0 0 0 0
1 0
26 0
-0.55 [-1.33, 0.24] Not estimable
0 2
Not estimable Subtotals only

298
2.1 Calcipotriol vs. propylthiouracil cream 2.2 Calcipotriol vs. tacrolimus ointment 2.3 Calcipotriol vs. tazarotene 2.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 2.5 Calcipotriol vs. vitamin B12 cream 2.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 2.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 3 PASI 3.1 Calcipotriol vs. propylthiouracil cream 3.2 Calcipotriol vs. tacrolimus ointment 3.3 Calcipotriol vs. tazarotene 3.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 3.5 Calcipotriol vs. vitamin B12 cream 3.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 3.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 4 PAGI 4.1 Calcipotriol vs. propylthiouracil cream 4.2 Calcipotriol vs. tacrolimus ointment 4.3 Calcipotriol vs. tazarotene 4.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 4.5 Calcipotriol vs. vitamin B12 cream 4.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 4.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks)
0 1 1 0
0 47 199 0
Not estimable -0.95 [-1.55, -0.34] -0.05 [-0.33, 0.23] Not estimable
0 0
0 0
0 4 1 0 0 0
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
Not estimable Subtotals only -2.24 [-3.23, -1.25] Not estimable Not estimable Not estimable
27 0 0 0
1 1
26 650
-0.01 [-0.78, 0.75] 0.23 [0.07, 0.38]
1 1 0 0 0 0
413
Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI) Std. Mean Difference (IV, Random, 95% CI)
0.78 [0.58, 0.98] Subtotals only Not estimable Not estimable Not estimable Not estimable
0 0 0 0
1 0
26 0
-0.55 [-1.33, 0.24] Not estimable
Not estimable
299
5 Combined endpoint (IAGI/TSS/PASI/PAGI) 5.1 Calcipotriol vs. propylthiouracil cream 5.2 Calcipotriol vs. tacrolimus ointment 5.3 Calcipotriol vs. tazarotene 5.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 5.5 Calcipotriol vs. vitamin B12 cream 5.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 5.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 6 Total withdrawals 6.1 Calcipotriol vs. Propylthiouracil cream 6.2 Calcipotriol vs. tacrolimus ointment 6.3 Calcipotriol vs. tazarotene 6.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 6.5 Calcipotriol vs. vitamin B12 cream 6.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) 6.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 7 Withdrawals due to adverse events 7.1 Calcipotriol vs. Propylthiouracil cream 7.2 Calcipotriol vs. tacrolimus ointment 7.3 Calcipotriol vs. tazarotene 7.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 7.5 Calcipotriol vs. vitamin B12 cream 7.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks)
6 1 1 1 0 27 47 199 0
Subtotals only -2.24 [-3.23, -1.25] -0.95 [-1.55, -0.34] -0.05 [-0.33, 0.23] Not estimable
1 1
26 650
-0.55 [-1.33, 0.24] 0.23 [0.07, 0.38]
1 6 1 0 1 1
413
Std. Mean Difference (IV, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.78 [0.58, 0.98] Subtotals only 0.07 [-0.16, 0.30] Not estimable -0.05 [-0.10, 0.01] -0.03 [-0.15, 0.08]
28 0 208 120
1 1
26 649
Not estimable 0.08 [0.03, 0.13]
1 5 1 0 1 1
501
0.05 [-0.01, 0.12] Subtotals only 0.07 [-0.16, 0.30] Not estimable -0.02 [-0.07, 0.03] -0.02 [-0.10, 0.07]
28 0 208 120
1 0
26 0
300
7.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 8 Withdrawals due to treatment failure 8.1 Calcipotriol vs. Propylthiouracil cream 8.2 Calcipotriol vs. tacrolimus ointment 8.3 Calcipotriol vs. tazarotene 8.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 8.5 Calcipotriol vs. vitamin B12 cream 8.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) 8.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 9 Adverse events (local) 9.1 Calcipotriol vs. Propylthiouracil cream 9.2 Calcipotriol vs. tacrolimus ointment 9.3 Calcipotriol vs. tazarotene 9.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 9.5 Calcipotriol vs. vitamin B12 cream 9.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) 9.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) 10 Adverse events (systemic) 10.1 Calcipotriol vs. Propylthiouracil cream 10.2 Calcipotriol vs. tacrolimus ointment 10.3 Calcipotriol vs. tazarotene 10.4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream 10.5 Calcipotriol vs. vitamin B12 cream
1 5 1 0 1 1
501
0.02 [-0.01, 0.05] Subtotals only -0.07 [-0.25, 0.11] Not estimable Not estimable Not estimable
28 0 208 120
1 0
26 0
1 5 1 0 1 0
501
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.05 [0.02, 0.08] Subtotals only -0.07 [-0.25, 0.11] Not estimable -0.03 [-0.11, 0.06] Not estimable
28 0 204 0
1 1
26 649
0.23 [-0.06, 0.52] 0.11 [0.05, 0.17]
1 2 1 0 1 0
501
Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI) Risk Difference (M-H, Random, 95% CI)
0.06 [0.01, 0.11] Subtotals only Not estimable Not estimable -0.01 [-0.05, 0.03] Not estimable
28 0 183 0
Not estimable
301
10.6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) 10.7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks)
Not estimable
Not estimable
Analysis 1.1. Comparison 1 Vitamin D analogues vs. placebo, Outcome 1 IAGI.

Review: Topical treatments for chronic plaque psoriasis
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 1 IAGI
Study or subgroup
Vitamin D analogue N Mean(SD)
Placebo N Mean(SD)
Std. Mean Difference IV,Random,95% CI
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Green 1994 Guenther 2002 (P) Harrington 1996a Kang 1998 Kragballe 1988b Oranje 1997 Papp 2003 (P) 26 62 25 227 290 15 27 43 308 -3.19 (1.27) -2.66 (0.87) -2.52 (1.08) -3.3 (1.12) -2.05 (0.84) -3.87 (1.36) -2.4 (0.88) -2.53 (1.05) -2.81 (1.21) 28 62 24 206 71 15 27 34 107 -1.86 (0.89) -1.84 (0.75) -1.25 (1.22) -1.88 (1.14) -1.37 (0.91) -1.47 (0.99) -1.17 (0.62) -1.91 (1.19) -1.92 (1.07) 4.9 % 5.7 % 4.8 % 6.1 % 6.0 % 3.7 % 4.8 % 5.4 % 6.1 % -1.20 [ -1.79, -0.62 ] -1.00 [ -1.38, -0.63 ] -1.09 [ -1.69, -0.48 ] -1.25 [ -1.46, -1.05 ] -0.79 [ -1.06, -0.53 ] -1.96 [ -2.86, -1.07 ] -1.59 [ -2.21, -0.97 ] -0.55 [ -1.01, -0.09 ] -0.76 [ -0.98, -0.53 ]
Subtotal (95% CI)
1023
574
47.4 % -1.04 [ -1.27, -0.82 ]
Heterogeneity: Tau?? = 0.07; Chi?? = 24.87, df = 8 (P = 0.002); I?? =68% Test for overall effect: Z = 9.02 (P < 0.00001) 2 Calcitriol Langner 1992 Langner 1993 Langner 2001 (P) Perez 1996 29 32 15 84 -4.1 (1.05) -3.97 (1.33) -2.4 (1.18) -3.2 (0.85) 29 32 14 84 -3 (1.04) -3.28 (1.14) -2.14 (0.66) -1.14 (0.38) 5.0 % 5.2 % 4.3 % 5.4 % -1.04 [ -1.59, -0.49 ] -0.55 [ -1.05, -0.05 ] -0.26 [ -0.99, 0.47 ] -3.11 [ -3.57, -2.66 ]
Subtotal (95% CI)
160
159
19.9 %
-1.25 [ -2.63, 0.12 ]
Heterogeneity: Tau?? = 1.88; Chi?? = 76.40, df = 3 (P<0.00001); I?? =96% Test for overall effect: Z = 1.79 (P = 0.073)
-10
-5
10
Favours vitamin D analogue
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Vitamin D analogue N 3 Tacalcitol van de Kerkhof 1996a 103 -1.66 (0.88) 103 -0.75 (0.72) 5.9 % Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
Continued) Std. Mean Difference
IV,Random,95% CI
-1.13 [ -1.42, -0.83 ]
Subtotal (95% CI)

Heterogeneity: not applicable
103
103
5.9 % -1.13 [ -1.42, -0.83 ]
Test for overall effect: Z = 7.51 (P < 0.00001) 4 Dovobet, OD Guenther 2002 (P) 150 -3.59 (1) 206 -1.88 (1.14) 6.0 % -1.58 [ -1.82, -1.33 ]
Subtotal (95% CI)

150
206
6.0 % -1.58 [ -1.82, -1.33 ]
Test for overall effect: Z = 12.84 (P < 0.00001) 5 Dovobet, BD Guenther 2002 (P) Papp 2003 (P) 234 301 -3.79 (0.97) -3.84 (0.91) 206 107 -1.88 (1.14) -1.92 (1.07) 6.1 % 6.0 % -1.81 [ -2.03, -1.59 ] -2.01 [ -2.27, -1.75 ]
Subtotal (95% CI)
535
313
12.1 % -1.90 [ -2.09, -1.71 ]
Heterogeneity: Tau?? = 0.00; Chi?? = 1.27, df = 1 (P = 0.26); I?? =22% Test for overall effect: Z = 19.38 (P < 0.00001) 6 Maxacalcitol Barker 1999 (P) 75 -3.52 (1.23) 28 -1.86 (0.89) 5.3 % -1.43 [ -1.91, -0.96 ]
Subtotal (95% CI)

75
28
5.3 % -1.43 [ -1.91, -0.96 ]
Test for overall effect: Z = 5.88 (P < 0.00001) 7 Paricalcitol OD Durakovic 2004 11 -2.45 (1.09) 11 -0.69 (0.94) 3.4 % -1.66 [ -2.66, -0.67 ]
Subtotal (95% CI)

11
11
3.4 % -1.66 [ -2.66, -0.67 ]
Test for overall effect: Z = 3.27 (P = 0.0011)
Total (95% CI)
2057
1394
100.0 % -1.30 [ -1.57, -1.03 ]
Heterogeneity: Tau?? = 0.30; Chi?? = 187.00, df = 18 (P<0.00001); I?? =90% Test for overall effect: Z = 9.45 (P < 0.00001)
-10
-5
10
Favours placebo
303
Analysis 1.2. Comparison 1 Vitamin D analogues vs. placebo, Outcome 2 TSS.

Comparison: 1 Vitamin D analogues vs. placebo Outcome: 2 TSS
Study or subgroup
Placebo N Mean(SD)
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Green 1994 Highton 1995 Kang 1998 Kaufmann 2002 (P) Kragballe 1988b Pariser 1996 Staberg 1998b Zonneveld 1998 (P) 26 61 25 124 15 480 27 167 9 23 2.8 (2.3) 3.15 (1.91) 3.6 (2.7) 1.7 (1.14) 4.53 (3.16) 2.24 (0.9) 4.63 (1.88) 2.27 (1.26) 1.3 (1.6) 2.6 (1.64) 28 61 24 123 15 157 27 168 9 23 8.3 (3.2) 4.68 (1.91) 5.3 (2.5) 3.15 (1.14) 10.8 (3.16) 2.68 (0.89) 6.73 (1.37) 3.63 (1.26) 4.6 (2.2) 4.6 (1.64) 5.3 % 6.2 % 5.6 % 6.5 % 4.5 % 6.6 % 5.5 % 6.6 % 3.8 % 5.4 % -1.93 [ -2.59, -1.28 ] -0.80 [ -1.17, -0.43 ] -0.64 [ -1.22, -0.07 ] -1.27 [ -1.54, -0.99 ] -1.93 [ -2.82, -1.04 ] -0.49 [ -0.67, -0.31 ] -1.26 [ -1.85, -0.67 ] -1.08 [ -1.31, -0.85 ] -1.63 [ -2.74, -0.53 ] -1.20 [ -1.83, -0.57 ]
Subtotal (95% CI)
957
635
56.0 % -1.13 [ -1.43, -0.83 ]
Heterogeneity: Tau?? = 0.16; Chi?? = 48.52, df = 9 (P<0.00001); I?? =81% Test for overall effect: Z = 7.38 (P < 0.00001) 2 Calcitriol Perez 1996 van de Kerkhof 1989 84 10 2.8 (1.5) 6 (1.47) 84 10 7.1 (0.1) 6.1 (1.47) 5.7 % 4.5 % -4.03 [ -4.56, -3.50 ] -0.07 [ -0.94, 0.81 ]
Subtotal (95% CI)

Test for overall effect: Z = 1.04 (P = 0.30) 3 Tacalcitol Scarpa 1997 Seidenari 1997 (P) van de Kerkhof 1996a
94
94
10.3 %
-2.06 [ -5.94, 1.82 ]
Heterogeneity: Tau?? = 7.71; Chi?? = 57.41, df = 1 (P<0.00001); I?? =98%
134 11 103
3.44 (1.91) 2.92 (1.93) -4 (2.06)
134 11 103
4.34 (1.91) 4.52 (1.38) -2.3 (2.06)
6.5 % 4.5 % 6.4 %
-0.47 [ -0.71, -0.23 ] -0.92 [ -1.81, -0.03 ] -0.82 [ -1.11, -0.54 ]
Subtotal (95% CI)
248
248
17.5 % -0.66 [ -0.95, -0.37 ]
Heterogeneity: Tau?? = 0.03; Chi?? = 3.83, df = 2 (P = 0.15); I?? =48% Test for overall effect: Z = 4.50 (P < 0.00001) 4 Dovobet, OD Kaufmann 2002 (P) 490 1.5 (0.9) 157 2.68 (0.89)
-10 -5 0 5 10
6.6 %
-1.31 [ -1.51, -1.12 ]
Favours placebo
(Continued . . . )
304
(. . .
Study or subgroup Vitamin D analogue N Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

490
157
6.6 % -1.31 [ -1.51, -1.12 ]
Test for overall effect: Z = 13.30 (P < 0.00001) 5 Dovobet, BD
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Maxacalcitol Barker 1999 (P)
0.0 %
0.0 [ 0.0, 0.0 ]
75
3.13 (3.24)
28
8.38 (3.2)
5.9 %
-1.61 [ -2.10, -1.12 ]
Subtotal (95% CI)

75
28
5.9 % -1.61 [ -2.10, -1.12 ]
Test for overall effect: Z = 6.47 (P < 0.00001) 7 Paricalcitol OD Durakovic 2004 11 2.7 (1.7) 11 7.6 (2.6) 3.8 % -2.15 [ -3.24, -1.06 ]
Subtotal (95% CI)

11
11
3.8 % -2.15 [ -3.24, -1.06 ]
Total (95% CI)
1875
1173
100.0 % -1.28 [ -1.60, -0.95 ]
-10
-5
10
Favours placebo
305
Analysis 1.3. Comparison 1 Vitamin D analogues vs. placebo, Outcome 3 PASI.

Comparison: 1 Vitamin D analogues vs. placebo Outcome: 3 PASI
Study or subgroup
Placebo N Mean(SD)
Weight
1 Calcipotriol Dubertret 1992 Guenther 2002 (P) Harrington 1996a Kaufmann 2002 (P) Mortensen 1993b Oranje 1997 Papp 2003 (P) 65 227 296 480 17 43 308 6.3 (6.45) 4.2 (3.3) -4.3 (5.13) -0.46 (0.31) 6.53 (2.49) -0.52 (0.45) -0.49 (0.32) 65 207 70 157 17 34 107 9.16 (8.34) 7.7 (5.5) -0.8 (5.4) -0.23 (0.34) 9.04 (4.71) -0.37 (0.4) -0.29 (0.31) 8.8 % 9.8 % 9.4 % 9.8 % 6.1 % 8.0 % 9.6 % -0.38 [ -0.73, -0.03 ] -0.78 [ -0.97, -0.58 ] -0.67 [ -0.94, -0.41 ] -0.72 [ -0.91, -0.54 ] -0.65 [ -1.34, 0.04 ] -0.35 [ -0.80, 0.11 ] -0.63 [ -0.85, -0.40 ]
Subtotal (95% CI)
1436
657
61.4 % -0.66 [ -0.76, -0.56 ]
Heterogeneity: Tau?? = 0.00; Chi?? = 6.26, df = 6 (P = 0.40); I?? =4% Test for overall effect: Z = 12.92 (P < 0.00001) 2 Calcitriol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Tacalcitol
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Dovobet, OD Guenther 2002 (P) Kaufmann 2002 (P)
0.0 %
0.0 [ 0.0, 0.0 ]
150 490
3 (2.5) -0.71 (0.26)
207 157
7.7 (5.5) -0.23 (0.34)
9.6 % 9.7 %
-1.04 [ -1.27, -0.82 ] -1.70 [ -1.91, -1.50 ]
Subtotal (95% CI)
640
364
19.4 % -1.38 [ -2.02, -0.73 ]
Heterogeneity: Tau?? = 0.21; Chi?? = 18.34, df = 1 (P = 0.00002); I?? =95% Test for overall effect: Z = 4.17 (P = 0.000030) 5 Dovobet, BD Guenther 2002 (P) Papp 2003 (P) 234 301 2.7 (2.5) -0.73 (0.25) 207 107 7.7 (5.5) -0.29 (0.31) 9.7 % 9.5 % -1.19 [ -1.40, -0.99 ] -1.65 [ -1.89, -1.40 ]
Subtotal (95% CI)
535
314
19.2 % -1.41 [ -1.86, -0.97 ]
Heterogeneity: Tau?? = 0.09; Chi?? = 7.65, df = 1 (P = 0.01); I?? =87%
-4
-2
Favours placebo
(Continued . . . )
306
(. . .
Study or subgroup Vitamin D analogue N Test for overall effect: Z = 6.25 (P < 0.00001) 6 Maxacalcitol Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Paricalcitol OD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable
0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
2611
1335
100.0 % -0.91 [ -1.18, -0.64 ]
-4
-2
Favours placebo
Analysis 1.4. Comparison 1 Vitamin D analogues vs. placebo, Outcome 4 PAGI.

Comparison: 1 Vitamin D analogues vs. placebo Outcome: 4 PAGI
Study or subgroup
Placebo N Mean(SD)
Weight
1 Calcipotriol Green 1994 Harrington 1996a Oranje 1997 25 291 43 -2.52 (0.96) -2.27 (0.97) -2.37 (1.02) 24 71 34 -1.42 (1.1) -1.51 (1.07) -1.91 (1.24) 19.2 % 52.0 % 28.8 % -1.05 [ -1.65, -0.45 ] -0.77 [ -1.03, -0.50 ] -0.41 [ -0.86, 0.05 ]
Subtotal (95% CI)
359
129
100.0 % -0.72 [ -1.01, -0.42 ]
Heterogeneity: Tau?? = 0.03; Chi?? = 3.11, df = 2 (P = 0.21); I?? =36% Test for overall effect: Z = 4.73 (P < 0.00001) 2 Calcitriol
Subtotal (95% CI)
0
-4 -2 0 2 4
0.0 %
0.0 [ 0.0, 0.0 ]
Favours placebo
(Continued . . . )
307
(. . .
Study or subgroup Vitamin D analogue N Heterogeneity: not applicable Test for overall effect: not applicable 3 Tacalcitol Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Dovobet, OD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Dovobet, BD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Maxacalcitol
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Paricalcitol OD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
359
129
100.0 % -0.72 [ -1.01, -0.42 ]
Heterogeneity: Tau?? = 0.03; Chi?? = 3.11, df = 2 (P = 0.21); I?? =36% Test for overall effect: Z = 4.73 (P < 0.00001)
-4
-2
Favours placebo
308
Analysis 1.5. Comparison 1 Vitamin D analogues vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Placebo N Mean(SD)
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Green 1994 Guenther 2002 (P) Harrington 1996a Highton 1995 Kang 1998 Kaufmann 2002 (P) Kragballe 1988b Mortensen 1993b Oranje 1997 Papp 2003 (P) Pariser 1996 Staberg 1998b Zonneveld 1998 (P) 26 62 25 227 290 124 15 480 27 17 43 308 167 9 23 -3.19 (1.27) -2.66 (0.87) -2.52 (1.08) -3.3 (1.12) -2.05 (0.84) 1.7 (1.14) -3.87 (1.36) 2.24 (0.9) -2.4 (0.88) 6.53 (2.49) -2.53 (1.05) -2.81 (1.21) 2.27 (1.26) 1.3 (1.6) 2.6 (1.64) 28 62 24 206 71 123 15 157 27 17 34 107 168 9 23 -1.86 (0.89) -1.84 (0.75) -1.25 (1.22) -1.88 (1.14) -1.37 (0.91) 3.15 (1.14) -1.47 (0.99) 2.68 (0.89) -1.17 (0.62) 9.04 (4.71) -1.91 (1.19) -1.92 (1.07) 3.63 (1.26) 4.6 (2.2) 4.6 (1.64) 3.2 % 3.8 % 3.2 % 4.1 % 4.0 % 4.0 % 2.4 % 4.2 % 3.1 % 2.9 % 3.6 % 4.1 % 4.1 % 2.0 % 3.1 % -1.20 [ -1.79, -0.62 ] -1.00 [ -1.38, -0.63 ] -1.09 [ -1.69, -0.48 ] -1.25 [ -1.46, -1.05 ] -0.79 [ -1.06, -0.53 ] -1.27 [ -1.54, -0.99 ] -1.96 [ -2.86, -1.07 ] -0.49 [ -0.67, -0.31 ] -1.59 [ -2.21, -0.97 ] -0.65 [ -1.34, 0.04 ] -0.55 [ -1.01, -0.09 ] -0.76 [ -0.98, -0.53 ] -1.08 [ -1.31, -0.85 ] -1.63 [ -2.74, -0.53 ] -1.20 [ -1.83, -0.57 ]
Subtotal (95% CI)
1843
1071
51.8 % -1.02 [ -1.21, -0.83 ]
Heterogeneity: Tau?? = 0.09; Chi?? = 58.99, df = 14 (P<0.00001); I?? =76% Test for overall effect: Z = 10.38 (P < 0.00001) 2 Calcitriol Langner 1992 Langner 1993 Langner 2001 (P) Perez 1996 van de Kerkhof 1989 29 32 15 84 10 -4.1 (1.05) -3.97 (1.33) -2.4 (1.18) -3.2 (0.85) 6 (1.47) 29 32 14 84 10 -3 (1.04) -3.28 (1.14) -2.14 (0.66) -1.14 (0.38) 6.1 (1.47)
-4 -2 0 2 4
3.3 % 3.5 % 2.8 % 3.6 % 2.5 %
-1.04 [ -1.59, -0.49 ] -0.55 [ -1.05, -0.05 ] -0.26 [ -0.99, 0.47 ] -3.11 [ -3.57, -2.66 ] -0.07 [ -0.94, 0.81 ]
Favours placebo
(Continued . . . )
309
(. . .
Study or subgroup Vitamin D analogue N Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)
170
169
15.7 %
-1.03 [ -2.25, 0.19 ]
Heterogeneity: Tau?? = 1.82; Chi?? = 86.04, df = 4 (P<0.00001); I?? =95% Test for overall effect: Z = 1.65 (P = 0.098) 3 Tacalcitol Scarpa 1997 Seidenari 1997 (P) van de Kerkhof 1996a 134 11 103 3.44 (1.91) 2.92 (1.93) -1.66 (0.88) 134 11 103 4.34 (1.91) 4.52 (1.38) -0.75 (0.72) 4.1 % 2.4 % 4.0 % -0.47 [ -0.71, -0.23 ] -0.92 [ -1.81, -0.03 ] -1.13 [ -1.42, -0.83 ]
Subtotal (95% CI)
248
248
10.5 % -0.82 [ -1.34, -0.29 ]
Heterogeneity: Tau?? = 0.16; Chi?? = 11.57, df = 2 (P = 0.003); I?? =83% Test for overall effect: Z = 3.05 (P = 0.0023) 4 Dovobet, OD Guenther 2002 (P) Kaufmann 2002 (P) 150 490 -3.59 (1) 1.5 (0.9) 206 157 -1.88 (1.14) 2.68 (0.89) 4.1 % 4.1 % -1.58 [ -1.82, -1.33 ] -1.31 [ -1.51, -1.12 ]
Subtotal (95% CI)
640
363
8.2 % -1.43 [ -1.69, -1.18 ]
Heterogeneity: Tau?? = 0.02; Chi?? = 2.77, df = 1 (P = 0.10); I?? =64% Test for overall effect: Z = 10.98 (P < 0.00001) 5 Dovobet, BD Guenther 2002 (P) Papp 2003 (P) 234 301 -3.79 (0.97) -3.84 (0.91) 206 107 -1.88 (1.14) -1.92 (1.07) 4.1 % 4.0 % -1.81 [ -2.03, -1.59 ] -2.01 [ -2.27, -1.75 ]
Subtotal (95% CI)
535
313
8.1 % -1.90 [ -2.09, -1.71 ]
Heterogeneity: Tau?? = 0.00; Chi?? = 1.27, df = 1 (P = 0.26); I?? =22% Test for overall effect: Z = 19.38 (P < 0.00001) 6 Maxacalcitol Barker 1999 (P) 75 -3.52 (1.23) 28 -1.86 (0.89) 3.5 % -1.43 [ -1.91, -0.96 ]
Subtotal (95% CI)

75
28
3.5 % -1.43 [ -1.91, -0.96 ]
Test for overall effect: Z = 5.88 (P < 0.00001) 7 Paricalcitol OD Durakovic 2004 11 -2.45 (1.09) 11 -0.69 (0.94) 2.2 % -1.66 [ -2.66, -0.67 ]
Subtotal (95% CI)

11
11
2.2 % -1.66 [ -2.66, -0.67 ]
Total (95% CI)
3522
2203
100.0 % -1.17 [ -1.38, -0.96 ]
-4
-2
Favours placebo
310
Analysis 1.6. Comparison 1 Vitamin D analogues vs. placebo, Outcome 6 Total withdrawals.
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Vitamin D analogue n/N
Placebo n/N
Risk Difference MH,Random,95% CI
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Green 1994 Guenther 2002 (P) Harrington 1996a Kang 1998 Kaufmann 2002 (P) Kiss 1996 Mortensen 1993b Oranje 1997 Papp 2003 (P) Staberg 1998b 4/30 4/66 1/25 23/231 30/326 0/15 39/480 3/30 0/17 6/43 27/308 0/10 2/30 4/66 2/24 34/208 17/87 0/15 25/157 3/30 0/17 3/34 12/108 0/10 2.1 % 4.5 % 2.5 % 5.6 % 4.1 % 2.9 % 5.7 % 2.1 % 3.3 % 2.3 % 5.4 % 1.7 % 0.07 [ -0.08, 0.22 ] 0.0 [ -0.08, 0.08 ] -0.04 [ -0.18, 0.09 ] -0.06 [ -0.13, 0.00 ] -0.10 [ -0.19, -0.01 ] 0.0 [ -0.12, 0.12 ] -0.08 [ -0.14, -0.02 ] 0.0 [ -0.15, 0.15 ] 0.0 [ -0.11, 0.11 ] 0.05 [ -0.09, 0.19 ] -0.02 [ -0.09, 0.04 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
1581
786
42.2 %
-0.04 [ -0.06, -0.01 ]
Total events: 137 (Vitamin D analogue), 102 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 10.69, df = 11 (P = 0.47); I?? =0.0% Test for overall effect: Z = 2.69 (P = 0.0071) 2 Calcitriol Langner 1992 Langner 1993 Langner 2001 (P) Perez 1996 van de Kerkhof 1989 1/32 0/29 1/15 0/84 0/10 1/32 0/29 3/14 0/84 0/10 4.3 % 5.5 % 0.9 % 8.1 % 1.7 % 0.0 [ -0.09, 0.09 ] 0.0 [ -0.06, 0.06 ] -0.15 [ -0.40, 0.10 ] 0.0 [ -0.02, 0.02 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
170
169
20.5 %
0.00 [ -0.02, 0.02 ]
Total events: 2 (Vitamin D analogue), 4 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 2.53, df = 4 (P = 0.64); I?? =0.0% Test for overall effect: Z = 0.10 (P = 0.92)
-1
-0.5
0.5
Favours placebo
(Continued . . . )
311
(. . .
Study or subgroup Vitamin D analogue n/N 3 Tacalcitol Scarpa 1997 Seidenari 1997 (P) van de Kerkhof 1996a 23/157 1/12 19/122 23/157 1/12 19/122 4.7 % 1.1 % 4.1 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Risk Difference MH,Random,95% CI 0.0 [ -0.08, 0.08 ] 0.0 [ -0.22, 0.22 ] 0.0 [ -0.09, 0.09 ]
Subtotal (95% CI)
291
291
9.9 %
0.0 [ -0.06, 0.06 ]
Total events: 43 (Vitamin D analogue), 43 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 2 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 4 Dovobet, OD Guenther 2002 (P) Kaufmann 2002 (P) 11/152 13/490 34/208 25/157 5.5 % 5.9 % -0.09 [ -0.16, -0.03 ] -0.13 [ -0.19, -0.07 ]
Subtotal (95% CI)
642
365
11.4 %
-0.11 [ -0.16, -0.07 ]
Total events: 24 (Vitamin D analogue), 59 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.87, df = 1 (P = 0.35); I?? =0.0% Test for overall effect: Z = 5.11 (P < 0.00001) 5 Dovobet BD Guenther 2002 (P) Papp 2003 (P) 19/237 16/304 34/208 12/108 5.7 % 5.5 % -0.08 [ -0.14, -0.02 ] -0.06 [ -0.12, 0.01 ]
Subtotal (95% CI)
541
316
11.3 %
-0.07 [ -0.12, -0.03 ]
Total events: 35 (Vitamin D analogue), 46 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.30, df = 1 (P = 0.58); I?? =0.0% Test for overall effect: Z = 3.17 (P = 0.0015) 6 Maxacalcitol Barker 1999 (P) 16/90 2/30 2.9 % 0.11 [ -0.01, 0.23 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.83 (P = 0.068) 7 Paricalcitol OD Durakovic 2004
90
30
2.9 %
0.11 [ -0.01, 0.23 ]
Total events: 16 (Vitamin D analogue), 2 (Placebo)
0/11
0/11
1.9 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0)
11
11
1.9 %
0.0 [ -0.16, 0.16 ]
Total (95% CI)
3326
1968
100.0 %
-0.03 [ -0.06, -0.01 ]
Total events: 257 (Vitamin D analogue), 256 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 56.37, df = 25 (P = 0.00032); I?? =56% Test for overall effect: Z = 2.41 (P = 0.016)
-1
-0.5
0.5
Favours placebo
312
Analysis 1.7. Comparison 1 Vitamin D analogues vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Placebo n/N
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Green 1994 Guenther 2002 (P) Harrington 1996a Highton 1995 Kang 1998 Kaufmann 2002 (P) Kiss 1996 Mortensen 1993b Staberg 1998b 0/30 2/66 1/25 6/227 8/326 6/139 0/15 15/480 0/30 0/17 0/10 1/30 1/66 0/24 21/208 8/174 8/138 0/15 12/157 0/30 0/17 0/10 3.4 % 5.3 % 2.7 % 5.6 % 6.2 % 5.2 % 2.3 % 5.6 % 4.6 % 2.6 % 1.3 % -0.03 [ -0.12, 0.05 ] 0.02 [ -0.04, 0.07 ] 0.04 [ -0.07, 0.15 ] -0.07 [ -0.12, -0.03 ] -0.02 [ -0.06, 0.01 ] -0.01 [ -0.07, 0.04 ] 0.0 [ -0.12, 0.12 ] -0.05 [ -0.09, 0.00 ] 0.0 [ -0.06, 0.06 ] 0.0 [ -0.11, 0.11 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
1365
869
44.7 %
-0.02 [ -0.04, 0.00 ]
Total events: 38 (Vitamin D analogue), 51 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 11.35, df = 10 (P = 0.33); I?? =12% Test for overall effect: Z = 2.28 (P = 0.022) 2 Calcitriol Langner 1992 Langner 1993 Langner 2001 (P) Perez 1996 van de Kerkhof 1989 0/29 1/32 1/15 0/84 0/10 0/29 1/32 3/14 0/84 0/10 4.5 % 3.5 % 0.7 % 6.8 % 1.3 % 0.0 [ -0.06, 0.06 ] 0.0 [ -0.09, 0.09 ] -0.15 [ -0.40, 0.10 ] 0.0 [ -0.02, 0.02 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
170
169
16.7 %
0.00 [ -0.02, 0.02 ]
Total events: 2 (Vitamin D analogue), 4 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 2.53, df = 4 (P = 0.64); I?? =0.0% Test for overall effect: Z = 0.10 (P = 0.92) 3 Tacalcitol
-1
-0.5
0.5
Favours placebo
(Continued . . . )
313
(. . .
Study or subgroup Vitamin D analogue n/N Scarpa 1997 Seidenari 1997 (P) van de Kerkhof 1996a 1/157 0/12 1/122 Placebo n/N 0/157 0/12 0/122 Risk Difference MH,Random,95% CI Weight
Continued)
7.0 % 1.7 % 6.8 %
Subtotal (95% CI)
291
291
15.6 %
0.01 [ -0.01, 0.02 ]
Total events: 2 (Vitamin D analogue), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.02, df = 2 (P = 0.99); I?? =0.0% Test for overall effect: Z = 1.00 (P = 0.32) 4 Dovobet, OD Guenther 2002 (P) Kaufmann 2002 (P) 0/151 3/490 21/208 12/157 5.8 % 5.8 % -0.10 [ -0.14, -0.06 ] -0.07 [ -0.11, -0.03 ]
Subtotal (95% CI)
641
365
11.6 %
-0.09 [ -0.12, -0.06 ]
Total events: 3 (Vitamin D analogue), 33 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 1.04, df = 1 (P = 0.31); I?? =4% Test for overall effect: Z = 5.52 (P < 0.00001) 5 Dovobet BD Guenther 2002 (P) 1/235 21/208 5.8 % -0.10 [ -0.14, -0.05 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 4.54 (P < 0.00001) 6 Maxacalcitol Barker 1999 (P)
235
208
5.8 %
-0.10 [ -0.14, -0.05 ]
2/90
1/30
4.1 %
-0.01 [ -0.08, 0.06 ]
Subtotal (95% CI)

Total events: 2 (Vitamin D analogue), 1 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.31 (P = 0.76) 7 Paricalcitol OD Durakovic 2004
90
30
4.1 %
-0.01 [ -0.08, 0.06 ]
0/11
0/11
1.5 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

11
11
1.5 %
0.0 [ -0.16, 0.16 ]
Total (95% CI)
2803
1943
100.0 %
-0.02 [ -0.05, 0.00 ]
Total events: 48 (Vitamin D analogue), 110 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 94.72, df = 23 (P<0.00001); I?? =76% Test for overall effect: Z = 2.16 (P = 0.031)
-1
-0.5
0.5
Favours placebo
314
Analysis 1.8. Comparison 1 Vitamin D analogues vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Placebo n/N
Weight
1 Calcipotriol Barker 1999 (P) Green 1994 Guenther 2002 (P) Harrington 1996a Staberg 1998b 0/30 0/25 2/227 9/326 0/10 1/30 2/24 19/208 22/174 0/10 7.3 % 5.5 % 9.3 % 8.9 % 4.0 % -0.03 [ -0.12, 0.05 ] -0.08 [ -0.21, 0.05 ] -0.08 [ -0.12, -0.04 ] -0.10 [ -0.15, -0.05 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
618
446
35.0 %
-0.08 [ -0.11, -0.05 ]
Total events: 11 (Vitamin D analogue), 44 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 2.55, df = 4 (P = 0.64); I?? =0.0% Test for overall effect: Z = 5.38 (P < 0.00001) 2 Calcitriol Langner 1993 Langner 2001 (P) Perez 1996 van de Kerkhof 1989 0/32 0/15 0/84 0/10 1/32 3/14 0/84 0/10 7.5 % 2.8 % 9.8 % 4.0 % -0.03 [ -0.11, 0.05 ] -0.21 [ -0.44, 0.02 ] 0.0 [ -0.02, 0.02 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
141
140
24.1 %
-0.03 [ -0.12, 0.05 ]
Total events: 0 (Vitamin D analogue), 4 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 8.79, df = 3 (P = 0.03); I?? =66% Test for overall effect: Z = 0.74 (P = 0.46) 3 Tacalcitol Scarpa 1997 0/157 0/157 10.0 % 0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Dovobet, OD Guenther 2002 (P)
157
157
10.0 %
0.0 [ -0.01, 0.01 ]
0/151
19/208
9.3 %
-0.09 [ -0.13, -0.05 ]
Subtotal (95% CI)
151
208
9.3 %
-0.09 [ -0.13, -0.05 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
315
(. . .
Study or subgroup Vitamin D analogue n/N Heterogeneity: not applicable Test for overall effect: Z = 4.42 (P < 0.00001) 5 Dovobet BD Guenther 2002 (P) 1/235 19/208 9.3 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
-0.09 [ -0.13, -0.05 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 4.26 (P = 0.000020) 6 Maxacalcitol Barker 1999 (P)
235
208
9.3 %
-0.09 [ -0.13, -0.05 ]
0/90
1/30
7.8 %
-0.03 [ -0.11, 0.04 ]
Subtotal (95% CI)

90
30
7.8 %
-0.03 [ -0.11, 0.04 ]
0/11
0/11
4.4 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

11
11
4.4 %
0.0 [ -0.16, 0.16 ]
Total (95% CI)
1403
1200
100.0 %
-0.05 [ -0.10, -0.01 ]
Total events: 12 (Vitamin D analogue), 87 (Placebo) Heterogeneity: Tau?? = 0.01; Chi?? = 154.60, df = 13 (P<0.00001); I?? =92% Test for overall effect: Z = 2.22 (P = 0.027)
-1
-0.5
0.5
Favours placebo
316
Analysis 1.9. Comparison 1 Vitamin D analogues vs. placebo, Outcome 9 Adverse events (local).
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Placebo n/N
Weight
1 Calcipotriol Highton 1995 Dubertret 1992 Green 1994 Guenther 2002 (P) Harrington 1996a Kang 1998 Kaufmann 2002 (P) Kiss 1996 Oranje 1997 Papp 2003 (P) Staberg 1998b 28/139 14/66 5/25 45/227 81/326 2/15 54/480 0/30 7/43 53/308 1/10 21/138 16/66 7/24 26/208 20/87 0/15 21/157 0/30 8/34 17/108 1/10 2.9 % 1.2 % 0.4 % 5.0 % 2.4 % 0.6 % 6.4 % 5.9 % 0.7 % 3.6 % 0.3 % 0.05 [ -0.04, 0.14 ] -0.03 [ -0.17, 0.11 ] -0.09 [ -0.33, 0.15 ] 0.07 [ 0.00, 0.14 ] 0.02 [ -0.08, 0.12 ] 0.13 [ -0.06, 0.33 ] -0.02 [ -0.08, 0.04 ] 0.0 [ -0.06, 0.06 ] -0.07 [ -0.25, 0.11 ] 0.01 [ -0.07, 0.10 ] 0.0 [ -0.26, 0.26 ]
Subtotal (95% CI)
1669
877
29.5 %
0.01 [ -0.01, 0.04 ]
Total events: 290 (Vitamin D analogue), 137 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 8.40, df = 10 (P = 0.59); I?? =0.0% Test for overall effect: Z = 1.00 (P = 0.32) 2 Calcitriol Langner 1992 van de Kerkhof 1989 0/29 0/10 0/29 0/10 5.6 % 0.8 % 0.0 [ -0.06, 0.06 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

39
39
6.3 %
0.0 [ -0.06, 0.06 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 3 Tacalcitol Scarpa 1997 1/134 2/157 40.2 % -0.01 [ -0.03, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.45 (P = 0.65)
134
157
40.2 %
-0.01 [ -0.03, 0.02 ]
-0.5
-0.25
0.25
0.5
Favours placebo
(Continued . . . )
317
(. . .
Study or subgroup Vitamin D analogue n/N 4 Dovobet, OD Guenther 2002 (P) Kaufmann 2002 (P) 15/151 29/490 26/208 21/157 5.4 % 7.1 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Risk Difference MH,Random,95% CI -0.03 [ -0.09, 0.04 ] -0.07 [ -0.13, -0.02 ]
Subtotal (95% CI)
641
365
12.5 %
-0.05 [ -0.10, -0.01 ]
Total events: 44 (Vitamin D analogue), 47 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 1.21, df = 1 (P = 0.27); I?? =18% Test for overall effect: Z = 2.17 (P = 0.030) 5 Dovobet BD Guenther 2002 (P) Papp 2003 (P) 25/235 30/304 26/208 17/108 6.5 % 4.0 % -0.02 [ -0.08, 0.04 ] -0.06 [ -0.14, 0.02 ]
Subtotal (95% CI)
539
316
10.5 %
-0.03 [ -0.08, 0.01 ]
Total events: 55 (Vitamin D analogue), 43 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.66, df = 1 (P = 0.42); I?? =0.0% Test for overall effect: Z = 1.41 (P = 0.16) 6 Maxacalcitol
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 7 Paricalcitol OD Durakovic 2004
0.0 %
0.0 [ 0.0, 0.0 ]
0/11
0/11
0.9 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

11
11
0.9 %
0.0 [ -0.16, 0.16 ]
Total (95% CI)
3033
1765
100.0 %
-0.01 [ -0.02, 0.01 ]
Total events: 390 (Vitamin D analogue), 229 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 18.25, df = 18 (P = 0.44); I?? =1% Test for overall effect: Z = 1.04 (P = 0.30)
-0.5
-0.25
0.25
0.5
Favours placebo
318
Analysis 1.10. Comparison 1 Vitamin D analogues vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 1 Vitamin D analogues vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Placebo n/N
Weight
1 Calcipotriol Barker 1999 (P) Dubertret 1992 Harrington 1996a Kang 1998 Mortensen 1993b Oranje 1997 Papp 2003 (P) Staberg 1998b 0/30 0/66 0/326 0/15 0/17 0/43 0/308 0/10 0/30 0/66 0/87 0/15 0/17 0/34 0/108 0/10 1.1 % 5.0 % 16.1 % 0.3 % 0.4 % 1.7 % 23.6 % 0.1 % 0.0 [ -0.06, 0.06 ] 0.0 [ -0.03, 0.03 ] 0.0 [ -0.02, 0.02 ] 0.0 [ -0.12, 0.12 ] 0.0 [ -0.11, 0.11 ] 0.0 [ -0.05, 0.05 ] 0.0 [ -0.01, 0.01 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

815
367
48.4 %
0.0 [ -0.01, 0.01 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 7 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 2 Calcitriol Langner 1992 Perez 1996 0/29 0/84 0/29 0/84 1.0 % 8.1 % 0.0 [ -0.06, 0.06 ] 0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

113
113
9.1 %
0.0 [ -0.02, 0.02 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 3 Tacalcitol van de Kerkhof 1996a 0/122 0/122 16.9 % 0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Dovobet, OD
122
122
16.9 %
0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: not applicable
0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
319
(. . .
Study or subgroup Vitamin D analogue n/N Test for overall effect: not applicable 5 Dovobet BD Papp 2003 (P) 0/304 0/108 23.5 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Maxacalcitol Barker 1999 (P)
304
108
23.5 %
0.0 [ -0.01, 0.01 ]
0/90
0/30
1.9 %
0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)

90
30
1.9 %
0.0 [ -0.05, 0.05 ]
0/11
0/11
0.2 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

11
11
0.2 %
0.0 [ -0.16, 0.16 ]
Total (95% CI)
1455
751
100.0 %
0.0 [ -0.01, 0.01 ]
Total events: 0 (Vitamin D analogue), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 13 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
-1
-0.5
0.5
Favours placebo
320
Analysis 2.1. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 1 IAGI.

Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 1 IAGI
Study or subgroup
Corticosteroid (potent) N Mean(SD)
Placebo N Mean(SD)
Weight
1 Betamethasone dipropionate, maintenance
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Betamethasone dipropionate OD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Betamethasone dipropionate BD Elie 1983 Papp 2003 (P) Vanderploeg 1976 Wortzel 1975 (1) Wortzel 1975 (2)
0.0 %
0.0 [ 0.0, 0.0 ]
10 312 17 39 5
-1.8 (1) -3.44 (1.05) -3.24 (0.97) -2.97 (1.09) -2.2 (1.1)
10 107 16 37 4
-0.8 (1) -1.92 (1.07) -2.06 (0.93) -1.7 (1.15) -1.25 (0.5)
2.9 % 18.2 % 4.3 % 8.5 % 1.3 %
-0.96 [ -1.89, -0.02 ] -1.44 [ -1.68, -1.20 ] -1.21 [ -1.96, -0.46 ] -1.12 [ -1.61, -0.64 ] -0.94 [ -2.38, 0.49 ]
Subtotal (95% CI)
383
174
35.1 %
-1.34 [ -1.54, -1.14 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 2.45, df = 4 (P = 0.65); I?? =0.0% Test for overall effect: Z = 13.09 (P < 0.00001) 4 Betamethasone valerate Stein 2001 37 -3.1 (1.19) 37 -1.4 (1.19) 7.8 % -1.41 [ -1.93, -0.90 ]
Subtotal (95% CI)

37
37
7.8 %
-1.41 [ -1.93, -0.90 ]
Test for overall effect: Z = 5.41 (P < 0.00001) 5 Budesonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Desonide Greenspan 1993
0.0 %
0.0 [ 0.0, 0.0 ]
56
-2.8 (0.91)
20
-2 (0.91)
7.5 %
-0.87 [ -1.40, -0.34 ]
Subtotal (95% CI)

56
20
7.5 %
-0.87 [ -1.40, -0.34 ]
Test for overall effect: Z = 3.22 (P = 0.0013) 7 Diorasone diacetate
-10
-5
10
Favours corticosteroid
Favours placebo
(Continued . . . )
321
(. . .
Study or subgroup Corticosteroid (potent) N Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Fluticasone propionate Olsen 1996 (1) Olsen 1996 (2)
0.0 %
0.0 [ 0.0, 0.0 ]
88 105
-2.9 (1.37) -2.8 (1.22)
90 100
-1.7 (1.18) -1.7 (1.15)
14.6 % 15.6 %
-0.94 [ -1.25, -0.63 ] -0.92 [ -1.21, -0.64 ]
Subtotal (95% CI)
193
190
30.2 %
-0.93 [ -1.14, -0.72 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.00, df = 1 (P = 0.96); I?? =0.0% Test for overall effect: Z = 8.63 (P < 0.00001) 9 Hydrocortisone buteprate
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 10 Mometasone furoate Medansky 1987
0.0 %
0.0 [ 0.0, 0.0 ]
50
-1.96 (0.9)
45
-1.24 (1)
10.4 %
-0.75 [ -1.17, -0.34 ]
Subtotal (95% CI)

50
45
10.4 %
-0.75 [ -1.17, -0.34 ]
Test for overall effect: Z = 3.54 (P = 0.00041) 11 Fluocinolone acetonide, plus occlusion Pauporte 2004 42 -4.38 (0.99) 42 -2.76 (1.57) 8.9 % -1.22 [ -1.69, -0.76 ]
Subtotal (95% CI)

42
42
8.9 %
-1.22 [ -1.69, -0.76 ]
Test for overall effect: Z = 5.12 (P < 0.00001)
Total (95% CI)
761
508
100.0 %
-1.09 [ -1.26, -0.92 ]
-10
-5
10
Favours placebo
322
Analysis 2.2. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 2 TSS.

Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 2 TSS
Study or subgroup
Placebo N Mean(SD)
1 Betamethasone dipropionate, maintenance Katz 1987a 19 0.83 (1.26) 19 2.12 (1.26) -1.00 [ -1.68, -0.32 ]
Subtotal (95% CI)

19
19
-1.00 [ -1.68, -0.32 ]
Test for overall effect: Z = 2.89 (P = 0.0038) 2 Betamethasone dipropionate OD Kaufmann 2002 (P) Lane 1983 476 46 1.9 (0.94) 4.5 (2.65) 157 47 2.68 (0.89) 6.6 (2.65) -0.84 [ -1.03, -0.65 ] -0.79 [ -1.21, -0.36 ]
Subtotal (95% CI)
522
204
-0.83 [ -1.00, -0.66 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.05, df = 1 (P = 0.82); I?? =0.0% Test for overall effect: Z = 9.56 (P < 0.00001) 3 Betamethasone dipropionate BD Elie 1983 Vanderploeg 1976 10 17 2.18 (2.74) 3.2 (2.65) 10 16 3.87 (2.74) 5.4 (2.65) -0.59 [ -1.49, 0.31 ] -0.81 [ -1.52, -0.10 ]
Subtotal (95% CI)
27
26
-0.73 [ -1.28, -0.17 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.14, df = 1 (P = 0.71); I?? =0.0% Test for overall effect: Z = 2.54 (P = 0.011) 4 Betamethasone valerate Franz 1999 Ormerod 1997 Stein 2001 115 11 37 2.78 (2.74) 4.92 (2.53) 0 (0) 57 11 37 5.97 (2.74) 7.75 (2.45) 0 (0) -1.16 [ -1.50, -0.82 ] -1.09 [ -2.00, -0.18 ] 0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)
163
105
-1.15 [ -1.47, -0.83 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.02, df = 1 (P = 0.89); I?? =0.0% Test for overall effect: Z = 7.07 (P < 0.00001) 5 Budesonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Desonide Greenspan 1993
0.0 [ 0.0, 0.0 ]
56
3.07 (0.96)
20
4.11 (0.7)
-1.14 [ -1.69, -0.60 ]
Subtotal (95% CI)
56
20
-10 -5 0 5 10
-1.14 [ -1.69, -0.60 ]
Favours placebo
(Continued . . . )
323
(. . .
Study or subgroup Corticosteroid (potent) N Heterogeneity: not applicable Test for overall effect: Z = 4.12 (P = 0.000038) 7 Diorasone diacetate Lane 1983 46 5.7 (2.65) 47 6.6 (2.65) Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI
IV,Random,95% CI
-0.34 [ -0.75, 0.07 ]
Subtotal (95% CI)

46
47
-0.34 [ -0.75, 0.07 ]
Test for overall effect: Z = 1.61 (P = 0.11) 8 Fluticasone propionate
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 9 Hydrocortisone buteprate Sears 1997
0.0 [ 0.0, 0.0 ]
78
-2 (1.69)
83
-1.3 (1.32)
-0.46 [ -0.77, -0.15 ]
Subtotal (95% CI)

78
83
-0.46 [ -0.77, -0.15 ]
Test for overall effect: Z = 2.89 (P = 0.0039) 10 Mometasone furoate Medansky 1987 50 2.7 (1.26) 45 4.2 (1.26) -1.18 [ -1.62, -0.74 ]
Subtotal (95% CI)

50
45
-1.18 [ -1.62, -0.74 ]
Test for overall effect: Z = 5.29 (P < 0.00001) 11 Fluocinolone acetonide, plus occlusion Pauporte 2004 42 3 (1.71) 42 4.76 (2.18) -0.89 [ -1.34, -0.44 ]
Subtotal (95% CI)

42
42
-0.89 [ -1.34, -0.44 ]
Total (95% CI)
1003
591
-0.84 [ -1.01, -0.67 ]
-10
-5
10
Favours placebo
324
Analysis 2.3. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 3 PASI.

Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 3 PASI
Study or subgroup
Placebo N Mean(SD)
Weight
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Betamethasone dipropionate OD Kaufmann 2002 (P)
0.0 %
0.0 [ 0.0, 0.0 ]
476
-0.57 (0.3)
157
-0.23 (0.34)
60.3 %
-1.09 [ -1.28, -0.90 ]
Subtotal (95% CI)

476
157
60.3 %
-1.09 [ -1.28, -0.90 ]
Test for overall effect: Z = 11.27 (P < 0.00001) 3 Betamethasone dipropionate BD Papp 2003 (P) 312 -0.63 (0.27) 107 -0.29 (0.31) 39.7 % -1.21 [ -1.44, -0.97 ]
Subtotal (95% CI)

312
107
39.7 %
-1.21 [ -1.44, -0.97 ]
Test for overall effect: Z = 10.11 (P < 0.00001) 4 Betamethasone valerate
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Budesonide
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Desonide
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Diorasone diacetate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Fluticasone propionate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
325
(. . .
Study or subgroup Corticosteroid (potent) N 9 Hydrocortisone buteprate Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 10 Hydrocortisone buteprate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
11 Fluocinolone acetonide, plus occlusion
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
788
264
100.0 %
-1.14 [ -1.29, -0.99 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.56, df = 1 (P = 0.46); I?? =0.0% Test for overall effect: Z = 15.12 (P < 0.00001)
-10
-5
10
Favours placebo
326
Analysis 2.5. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Placebo N Mean(SD)
Weight
1 Betamethasone dipropionate, maintenance Katz 1987a 19 0.83 (1.26) 19 2.12 (1.26) 3.6 % -1.00 [ -1.68, -0.32 ]
Subtotal (95% CI)

19
19
3.6 %
-1.00 [ -1.68, -0.32 ]
Test for overall effect: Z = 2.89 (P = 0.0038) 2 Betamethasone dipropionate OD Kaufmann 2002 (P) Lane 1983 476 46 1.9 (0.94) 4.5 (2.65) 157 47 2.68 (0.89) 6.6 (2.65) 9.3 % 6.1 % -0.84 [ -1.03, -0.65 ] -0.79 [ -1.21, -0.36 ]
Subtotal (95% CI)
522
204
15.4 %
-0.83 [ -1.00, -0.66 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.05, df = 1 (P = 0.82); I?? =0.0% Test for overall effect: Z = 9.56 (P < 0.00001) 3 Betamethasone dipropionate BD Elie 1983 Papp 2003 (P) Vanderploeg 1976 Wortzel 1975 (1) Wortzel 1975 (2) 10 312 17 39 5 -1.8 (1) -3.44 (1.05) -3.24 (0.97) -2.97 (1.09) -2.2 (1.1) 10 107 16 37 4 -0.8 (1) -1.92 (1.07) -2.06 (0.93) -1.7 (1.15) -1.25 (0.5) 2.3 % 8.6 % 3.2 % 5.3 % 1.1 % -0.96 [ -1.89, -0.02 ] -1.44 [ -1.68, -1.20 ] -1.21 [ -1.96, -0.46 ] -1.12 [ -1.61, -0.64 ] -0.94 [ -2.38, 0.49 ]
Subtotal (95% CI)
383
174
20.4 %
-1.34 [ -1.54, -1.14 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 2.45, df = 4 (P = 0.65); I?? =0.0% Test for overall effect: Z = 13.09 (P < 0.00001) 4 Betamethasone valerate Franz 1999 Ormerod 1997 Stein 2001 115 11 37 2.78 (2.74) 4.92 (2.53) -3.1 (1.19) 57 11 37 5.97 (2.74) 7.75 (2.45) -1.4 (1.19) 7.2 % 2.4 % 5.1 % -1.16 [ -1.50, -0.82 ] -1.09 [ -2.00, -0.18 ] -1.41 [ -1.93, -0.90 ]
Subtotal (95% CI)
163
105
14.6 %
-1.22 [ -1.50, -0.95 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.75, df = 2 (P = 0.69); I?? =0.0% Test for overall effect: Z = 8.86 (P < 0.00001) 5 Budesonide
Subtotal (95% CI)
0
-10 -5 0 5 10
0.0 %
0.0 [ 0.0, 0.0 ]
Favours placebo
(Continued . . . )
327
(. . .
Study or subgroup Corticosteroid (potent) N Heterogeneity: not applicable Test for overall effect: not applicable 6 Desonide Greenspan 1993 56 -2.8 (0.91) 20 -2 (0.91) 4.9 % Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
-0.87 [ -1.40, -0.34 ]
Subtotal (95% CI)

56
20
4.9 %
-0.87 [ -1.40, -0.34 ]
Test for overall effect: Z = 3.22 (P = 0.0013) 7 Diorasone diacetate Lane 1983 46 5.7 (2.65) 47 6.6 (2.65) 6.3 % -0.34 [ -0.75, 0.07 ]
Subtotal (95% CI)

46
47
6.3 %
-0.34 [ -0.75, 0.07 ]
Test for overall effect: Z = 1.61 (P = 0.11) 8 Fluticasone propionate Olsen 1996 (1) Olsen 1996 (2) 88 105 -2.9 (1.37) -2.8 (1.22) 90 100 -1.7 (1.18) -1.7 (1.15) 7.6 % 7.9 % -0.94 [ -1.25, -0.63 ] -0.92 [ -1.21, -0.64 ]
Subtotal (95% CI)
193
190
15.5 %
-0.93 [ -1.14, -0.72 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.00, df = 1 (P = 0.96); I?? =0.0% Test for overall effect: Z = 8.63 (P < 0.00001) 9 Hydrocortisone buteprate Sears 1997 78 -2 (1.69) 83 -1.3 (1.32) 7.6 % -0.46 [ -0.77, -0.15 ]
Subtotal (95% CI)

78
83
7.6 %
-0.46 [ -0.77, -0.15 ]
Test for overall effect: Z = 2.89 (P = 0.0039) 10 Mometasone furoate Medansky 1987 50 -1.96 (0.9) 45 -1.24 (1) 6.2 % -0.75 [ -1.17, -0.34 ]
Subtotal (95% CI)

50
45
6.2 %
-0.75 [ -1.17, -0.34 ]
Test for overall effect: Z = 3.54 (P = 0.00041) 11 Fluocinolone acetonide, plus occlusion Pauporte 2004 42 -4.38 (0.99) 42 -2.76 (1.57) 5.5 % -1.22 [ -1.69, -0.76 ]
Subtotal (95% CI)

42
42
5.5 %
-1.22 [ -1.69, -0.76 ]
Total (95% CI)
1552
929
100.0 %
-0.95 [ -1.11, -0.80 ]
-10
-5
10
Favours placebo
328
Analysis 2.6. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 6 Total withdrawals.
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Corticosteroid (potent) n/N
Placebo n/N
Weight
1 Betamethasone dipropionate, maintenance Katz 1987a 6/20 16/20 4.3 % -0.50 [ -0.77, -0.23 ]
Subtotal (95% CI)

20
20
4.3 %
-0.50 [ -0.77, -0.23 ]
Total events: 6 (Corticosteroid (potent)), 16 (Placebo) Test for overall effect: Z = 3.68 (P = 0.00024) 2 Betamethasone dipropionate OD Kaufmann 2002 (P) 22/476 25/157 18.6 % -0.11 [ -0.17, -0.05 ]
Subtotal (95% CI)

476
157
18.6 %
-0.11 [ -0.17, -0.05 ]
Total events: 22 (Corticosteroid (potent)), 25 (Placebo) Test for overall effect: Z = 3.68 (P = 0.00024) 3 Betamethasone dipropionate BD Papp 2003 (P) 17/313 12/108 18.2 % -0.06 [ -0.12, 0.01 ]
Subtotal (95% CI)

313
108
18.2 %
-0.06 [ -0.12, 0.01 ]
Total events: 17 (Corticosteroid (potent)), 12 (Placebo) Test for overall effect: Z = 1.73 (P = 0.084) 4 Betamethasone valerate Stein 2001 3/40 3/40 12.6 % 0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 5 Budesonide Agrup 1981
40
40
12.6 %
0.0 [ -0.12, 0.12 ]
Total events: 3 (Corticosteroid (potent)), 3 (Placebo)
0/11
0/11
9.0 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Desonide Greenspan 1993
11
11
9.0 %
0.0 [ -0.16, 0.16 ]
4/60
5/20
-1 -0.5 0 0.5 1
6.7 %
-0.18 [ -0.38, 0.02 ]
Favours placebo
(Continued . . . )
329
(. . .
Study or subgroup Corticosteroid (potent) n/N Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.80 (P = 0.072) 7 Diorasone diacetate
60
20
6.7 %
-0.18 [ -0.38, 0.02 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
10/84
11/96
14.8 %
0.00 [ -0.09, 0.10 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.09 (P = 0.93) 10 Mometasone furoate
84
96
14.8 %
0.00 [ -0.09, 0.10 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 11 Fluocinolone acetonide, plus occlusion Pauporte 2004
0.0 %
0.0 [ 0.0, 0.0 ]
1/43
3/46
15.9 %
-0.04 [ -0.13, 0.04 ]
Subtotal (95% CI)

43
46
15.9 %
-0.04 [ -0.13, 0.04 ]
Total (95% CI)
1047
498
100.0 %
-0.07 [ -0.13, -0.01 ]
Total events: 63 (Corticosteroid (potent)), 75 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 19.27, df = 7 (P = 0.01); I?? =64% Test for overall effect: Z = 2.27 (P = 0.023)
-1
-0.5
0.5
Favours placebo
330
Analysis 2.7. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Placebo n/N
Weight
1 Betamethasone dipropionate, maintenance Katz 1987a Katz 1991a 0/20 0/48 0/20 0/46 6.4 % 14.6 % 0.0 [ -0.09, 0.09 ] 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI)
68
66
21.0 %
0.0 [ -0.04, 0.04 ]
Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 2 Betamethasone dipropionate OD Kaufmann 2002 (P) 5/476 12/157 14.2 % -0.07 [ -0.11, -0.02 ]
Subtotal (95% CI)

476
157
14.2 %
-0.07 [ -0.11, -0.02 ]
Total events: 5 (Corticosteroid (potent)), 12 (Placebo) Test for overall effect: Z = 3.04 (P = 0.0024) 3 Betamethasone dipropionate BD Elie 1983 Vanderploeg 1976 0/10 0/17 0/10 0/16 2.3 % 4.9 % 0.0 [ -0.17, 0.17 ] 0.0 [ -0.11, 0.11 ]
Subtotal (95% CI)
27
26
7.2 %
0.0 [ -0.09, 0.09 ]
Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 4 Betamethasone valerate Franz 1999 Stein 2001 0/115 3/40 0/57 0/40 17.8 % 6.4 % 0.0 [ -0.03, 0.03 ] 0.08 [ -0.02, 0.17 ]
Subtotal (95% CI)
155
97
24.2 %
0.03 [ -0.07, 0.13 ]
Total events: 3 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 4.71, df = 1 (P = 0.03); I?? =79% Test for overall effect: Z = 0.59 (P = 0.55) 5 Budesonide Agrup 1981 0/11 0/11 2.6 % 0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)
11
11
-1 -0.5 0 0.5 1
2.6 %
0.0 [ -0.16, 0.16 ]
Favours corticosteroid (potent)
Favours placebo
(Continued . . . )
331
(. . .
Study or subgroup Corticosteroid (potent) n/N Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Desonide Greenspan 1993 0/60 2/20 3.3 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
-0.10 [ -0.24, 0.04 ]
Subtotal (95% CI)

60
20
3.3 %
-0.10 [ -0.24, 0.04 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
1/94
0/96
17.3 %
0.01 [ -0.02, 0.04 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.72 (P = 0.47) 10 Mometasone furoate Medansky 1987
94
96
17.3 %
0.01 [ -0.02, 0.04 ]
0/61
3/59
10.1 %
-0.05 [ -0.11, 0.01 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.57 (P = 0.12) 11 Fluocinolone acetonide, plus occlusion
61
59
10.1 %
-0.05 [ -0.11, 0.01 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
952
532
100.0 %
-0.01 [ -0.04, 0.02 ]
-1
-0.5
0.5
Favours placebo
332
Analysis 2.8. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Placebo n/N
Weight
1 Betamethasone dipropionate, maintenance Katz 1987a Katz 1991a 5/20 16/46 15/20 35/44 45.5 % 54.5 % -0.50 [ -0.77, -0.23 ] -0.45 [ -0.63, -0.27 ]
Subtotal (95% CI)
66
64
100.0 %
-0.46 [ -0.61, -0.31 ]
Total events: 21 (Corticosteroid (potent)), 50 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.10, df = 1 (P = 0.75); I?? =0.0% Test for overall effect: Z = 6.04 (P < 0.00001) 2 Betamethasone dipropionate OD
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Betamethasone dipropionate BD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Betamethasone valerate Stein 2001
0.0 %
0.0 [ 0.0, 0.0 ]
0/40
0/40
100.0 %
0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 5 Budesonide Agrup 1981
40
40
100.0 %
0.0 [ -0.05, 0.05 ]
0/11
0/11
100.0 %
0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Desonide Greenspan 1993
11
11
100.0 %
0.0 [ -0.16, 0.16 ]
0/60
0/20
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)
60
20
-1 -0.5 0 0.5 1
100.0 %
0.0 [ -0.07, 0.07 ]
Favours placebo
(Continued . . . )
333
(. . .
Study or subgroup Corticosteroid (potent) n/N Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 7 Diorasone diacetate Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/94
0/96
100.0 %
0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 10 Mometasone furoate
94
96
100.0 %
0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 11 Fluocinolone acetonide, plus occlusion
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
334
Analysis 2.9. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 9 Adverse events (local).
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Placebo n/N
Weight
1 Betamethasone dipropionate, maintenance Katz 1987a Katz 1991a 0/20 0/48 0/20 0/46 7.9 % 16.1 % 0.0 [ -0.09, 0.09 ] 0.0 [ -0.04, 0.04 ]
Subtotal (95% CI)
68
66
24.0 %
0.0 [ -0.04, 0.04 ]
Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 2 Betamethasone dipropionate OD Kaufmann 2002 (P) 23/476 21/157 13.0 % -0.09 [ -0.14, -0.03 ]
Subtotal (95% CI)

476
157
13.0 %
-0.09 [ -0.14, -0.03 ]
Total events: 23 (Corticosteroid (potent)), 21 (Placebo) Test for overall effect: Z = 2.96 (P = 0.0031) 3 Betamethasone dipropionate BD Papp 2003 (P) Vanderploeg 1976 Elie 1983 27/313 0/17 0/10 17/108 0/16 0/10 10.0 % 6.2 % 3.0 % -0.07 [ -0.15, 0.00 ] 0.0 [ -0.11, 0.11 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
340
134
19.3 %
-0.04 [ -0.10, 0.02 ]
Total events: 27 (Corticosteroid (potent)), 17 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 1.71, df = 2 (P = 0.42); I?? =0.0% Test for overall effect: Z = 1.44 (P = 0.15) 4 Betamethasone valerate
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
335
(. . .
Study or subgroup Corticosteroid (potent) n/N Greenspan 1993 3/60 Placebo n/N 1/20 Risk Difference MH,Random,95% CI Weight
Continued)
Risk Difference MH,Random,95% CI 0.0 [ -0.11, 0.11 ]
6.2 %
Subtotal (95% CI)

60
20
6.2 %
0.0 [ -0.11, 0.11 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Fluticasone propionate Olsen 1996 (1)
0.0 %
0.0 [ 0.0, 0.0 ]
13/193
12/190
14.4 %
0.00 [ -0.05, 0.05 ]
Subtotal (95% CI)

193
190
14.4 %
0.00 [ -0.05, 0.05 ]
Total events: 13 (Corticosteroid (potent)), 12 (Placebo) Test for overall effect: Z = 0.17 (P = 0.87) 9 Hydrocortisone buteprate Sears 1997 21/94 27/96 5.3 % -0.06 [ -0.18, 0.07 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.92 (P = 0.36) 10 Mometasone furoate Medansky 1987
94
96
5.3 %
-0.06 [ -0.18, 0.07 ]
5/61
11/59
5.5 %
-0.10 [ -0.23, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.69 (P = 0.090) 11 Fluocinolone acetonide, plus occlusion Pauporte 2004
61
59
5.5 %
-0.10 [ -0.23, 0.02 ]
1/43
0/46
12.3 %
0.02 [ -0.04, 0.08 ]
Subtotal (95% CI)

43
46
12.3 %
0.02 [ -0.04, 0.08 ]
Total (95% CI)
1335
768
100.0 %
-0.02 [ -0.06, 0.01 ]
-1
-0.5
0.5
Favours placebo
336
Analysis 2.10. Comparison 2 Corticosteroid (potent) vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 2 Corticosteroid (potent) vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Placebo n/N
Weight
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Betamethasone dipropionate OD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Betamethasone dipropionate BD Papp 2003 (P)
0.0 %
0.0 [ 0.0, 0.0 ]
0/313
0/108
85.0 %
0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Betamethasone valerate
313
108
85.0 %
0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Diorasone diacetate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)
0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
337
(. . .
Study or subgroup Corticosteroid (potent) n/N Heterogeneity: not applicable Test for overall effect: not applicable 8 Fluticasone propionate Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 9 Hydrocortisone buteprate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 10 Mometasone furoate Medansky 1987
0.0 %
0.0 [ 0.0, 0.0 ]
0/61
0/59
15.0 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 11 Fluocinolone acetonide, plus occlusion
61
59
15.0 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
374
167
100.0 %
0.0 [ -0.01, 0.01 ]
Total events: 0 (Corticosteroid (potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
-1
-0.5
0.5
Favours placebo
338
Analysis 3.1. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 1 IAGI.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 1 IAGI
Study or subgroup
Corticosteroid (very potent) N Mean(SD)
Placebo N Mean(SD)
Weight
1 Amcinonide Ellis 1988 65 -4.6 (1.29) 67 -2.8 (1.23) 22.6 % -1.42 [ -1.80, -1.04 ]
Subtotal (95% CI)

65
67
22.6 % -1.42 [ -1.80, -1.04 ]
Test for overall effect: Z = 7.27 (P < 0.00001) 2 Clobetasol propionate Lebwohl 2002 Olsen 1991 60 188 -2.85 (1.47) -3.65 (1.24) 19 189 -1.58 (1.17) -1.7 (1.09) 16.8 % 29.2 % -0.89 [ -1.43, -0.36 ] -1.67 [ -1.90, -1.43 ]
Subtotal (95% CI)
248
208
46.0 % -1.32 [ -2.07, -0.57 ]
Heterogeneity: Tau?? = 0.25; Chi?? = 6.71, df = 1 (P = 0.01); I?? =85% Test for overall effect: Z = 3.43 (P = 0.00059) 3 Halcinonide Lepaw 1978 27 -2.3 (0.95) 27 -1.3 (0.82) 15.5 % -1.11 [ -1.69, -0.53 ]
Subtotal (95% CI)

27
27
15.5 % -1.11 [ -1.69, -0.53 ]
Test for overall effect: Z = 3.78 (P = 0.00016) 4 Halobetasol Bernhard 1991(2) 36 -2.97 (0.97) 33 -1.3 (0.85) 15.9 % -1.81 [ -2.37, -1.24 ]
Subtotal (95% CI)

36
33
15.9 % -1.81 [ -2.37, -1.24 ]
Total (95% CI)
376
335
100.0 % -1.42 [ -1.72, -1.11 ]
-10
-5
10
Favours corticosteroid (v potent)
Favours placebo
339
Analysis 3.2. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 2 TSS.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 2 TSS
Study or subgroup
Placebo N Mean(SD)
Weight
Subtotal (95% CI)

59
67
11.4 % -1.31 [ -1.70, -0.92 ]
Test for overall effect: Z = 6.64 (P < 0.00001) 2 Clobetasol propionate Franz 2000 Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Olsen 1991 125 139 95 35 188 2.1 (2.74) -4.01 (2.33) 3.2 (2.11) -4.3 (1.89) 2.4 (2.74) 63 140 47 39 189 5.4 (2.74) -1.51 (2.33) 5.49 (2.11) -1.6 (1.89) 6.3 (2.74) 15.5 % 24.7 % 12.2 % 6.7 % 29.5 % -1.20 [ -1.53, -0.87 ] -1.07 [ -1.32, -0.82 ] -1.08 [ -1.45, -0.71 ] -1.41 [ -1.93, -0.90 ] -1.42 [ -1.65, -1.19 ]
Subtotal (95% CI)
582
478
88.6 % -1.23 [ -1.39, -1.07 ]
Heterogeneity: Tau?? = 0.01; Chi?? = 5.42, df = 4 (P = 0.25); I?? =26% Test for overall effect: Z = 14.95 (P < 0.00001) 3 Halcinonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Halobetasol
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
641
545
100.0 % -1.24 [ -1.38, -1.11 ]
-10
-5
10
Favours placebo
340
Analysis 3.4. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 4 PAGI.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 4 PAGI
Study or subgroup
Placebo N Mean(SD)
Weight
Subtotal (95% CI)

65
67
23.1 % -0.97 [ -1.33, -0.61 ]
Test for overall effect: Z = 5.27 (P < 0.00001) 2 Clobetasol propionate Lebwohl 2002 60 -3.07 (1.4) 19 -1.68 (1.25) 10.3 % -1.01 [ -1.55, -0.47 ]
Subtotal (95% CI)

60
19
10.3 % -1.01 [ -1.55, -0.47 ]
Test for overall effect: Z = 3.65 (P = 0.00026) 3 Halcinonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Halobetasol Bernhard 1991 (1) Katz 1991b
0.0 %
0.0 [ 0.0, 0.0 ]
96 108
-2.92 (1.18) -2.46 (1.45)
96 108
-1.47 (1.29) -0.72 (1.14)
32.1 % 34.6 %
-1.17 [ -1.47, -0.86 ] -1.33 [ -1.62, -1.03 ]
Subtotal (95% CI)
204
204
66.6 % -1.25 [ -1.46, -1.04 ]
Total (95% CI)
329
290
100.0 % -1.16 [ -1.34, -0.99 ]
-10
-5
10
Favours placebo
341
Analysis 3.5. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Placebo N Mean(SD)
Weight
Subtotal (95% CI)

65
67
8.9 % -1.42 [ -1.80, -1.04 ]
Test for overall effect: Z = 7.27 (P < 0.00001) 2 Clobetasol propionate Franz 2000 Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Lebwohl 2002 Olsen 1991 125 139 95 35 60 188 2.1 (2.74) -4.01 (2.33) 3.2 (2.11) -4.3 (1.89) -2.85 (1.47) -3.65 (1.24) 63 140 47 39 19 189 5.4 (2.74) -1.51 (2.33) 5.49 (2.11) -1.6 (1.89) -1.58 (1.17) -1.7 (1.09) 10.4 % 12.6 % 9.2 % 6.4 % 6.0 % 13.2 % -1.20 [ -1.53, -0.87 ] -1.07 [ -1.32, -0.82 ] -1.08 [ -1.45, -0.71 ] -1.41 [ -1.93, -0.90 ] -0.89 [ -1.43, -0.36 ] -1.67 [ -1.90, -1.43 ]
Subtotal (95% CI)
642
497
57.8 % -1.24 [ -1.50, -0.98 ]
Heterogeneity: Tau?? = 0.07; Chi?? = 16.72, df = 5 (P = 0.01); I?? =70% Test for overall effect: Z = 9.49 (P < 0.00001) 3 Halcinonide Lepaw 1978 27 -2.3 (0.95) 27 -1.3 (0.82) 5.4 % -1.11 [ -1.69, -0.53 ]
Subtotal (95% CI)

27
27
5.4 % -1.11 [ -1.69, -0.53 ]
Test for overall effect: Z = 3.78 (P = 0.00016) 4 Halobetasol Bernhard 1991 (1) Bernhard 1991(2) Katz 1991b 96 36 108 -2.92 (1.18) -2.97 (0.97) -2.46 (1.45) 96 33 108 -1.47 (1.29) -1.3 (0.85) -0.72 (1.14) 11.0 % 5.6 % 11.3 % -1.17 [ -1.47, -0.86 ] -1.81 [ -2.37, -1.24 ] -1.33 [ -1.62, -1.03 ]
Subtotal (95% CI)
240
237
27.8 % -1.36 [ -1.65, -1.07 ]
Total (95% CI)
974
828
100.0 % -1.29 [ -1.45, -1.13 ]
-10
-5
10
Favours placebo
342
Analysis 3.6. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 6 Total withdrawals.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Corticosteroid (very potent) n/N
Placebo n/N
Weight
1 Amcinonide Ellis 1988 13/83 13/82 6.6 % 0.00 [ -0.11, 0.11 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.03 (P = 0.97) 2 Clobetasol propionate Franz 2000 Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Lebwohl 2002 Olsen 1991
83
82
6.6 %
0.00 [ -0.11, 0.11 ]
Total events: 13 (Corticosteroid (very potent)), 13 (Placebo)
0/125 4/139 1/95 6/44 3/61 5/189
0/63 4/140 0/47 15/45 2/20 22/189
17.6 % 15.5 % 15.7 % 3.5 % 4.7 % 13.7 %
0.0 [ -0.02, 0.02 ] 0.00 [ -0.04, 0.04 ] 0.01 [ -0.03, 0.05 ] -0.20 [ -0.37, -0.03 ] -0.05 [ -0.19, 0.09 ] -0.09 [ -0.14, -0.04 ]
Subtotal (95% CI)
653
504
70.7 %
-0.03 [ -0.09, 0.02 ]
Total events: 19 (Corticosteroid (very potent)), 43 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 35.97, df = 5 (P<0.00001); I?? =86% Test for overall effect: Z = 1.21 (P = 0.23) 3 Halcinonide Lepaw 1978 2/29 2/29 5.3 % 0.0 [ -0.13, 0.13 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Halobetasol Bernhard 1991(2)
29
29
5.3 %
0.0 [ -0.13, 0.13 ]
0/72
0/72
17.3 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)

72
72
17.3 %
0.0 [ -0.03, 0.03 ]
Total (95% CI)
837
687
100.0 %
-0.02 [ -0.06, 0.02 ]
Total events: 34 (Corticosteroid (very potent)), 58 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 33.44, df = 8 (P = 0.00005); I?? =76% Test for overall effect: Z = 1.11 (P = 0.27)
-1
-0.5
0.5
Favours placebo
343
Analysis 3.7. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Placebo n/N
Weight
1 Amcinonide Ellis 1988 1/83 0/82 4.9 % 0.01 [ -0.02, 0.04 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.72 (P = 0.47) 2 Clobetasol propionate Franz 2000 Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Lebwohl 2002 Olsen 1991
83
82
4.9 %
0.01 [ -0.02, 0.04 ]
0/125 0/139 0/95 1/44 0/61 0/189
0/63 1/140 0/47 1/45 0/20 1/189
9.0 % 13.7 % 5.1 % 1.4 % 1.1 % 25.0 %
0.0 [ -0.02, 0.02 ] -0.01 [ -0.03, 0.01 ] 0.0 [ -0.03, 0.03 ] 0.00 [ -0.06, 0.06 ] 0.0 [ -0.07, 0.07 ] -0.01 [ -0.02, 0.01 ]
Subtotal (95% CI)
653
504
55.4 %
0.00 [ -0.01, 0.01 ]
Total events: 1 (Corticosteroid (very potent)), 3 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.34, df = 5 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.83 (P = 0.41) 3 Halcinonide Lepaw 1978 0/29 0/29 1.3 % 0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Halobetasol Bernhard 1991 (1) Bernhard 1991(2) Katz 1991b
29
29
1.3 %
0.0 [ -0.06, 0.06 ]
0/100 0/72 0/110
0/100 0/72 0/110
14.1 % 7.4 % 17.0 %
0.0 [ -0.02, 0.02 ] 0.0 [ -0.03, 0.03 ] 0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)
282
282
-1 -0.5 0 0.5 1
38.5 %
0.0 [ -0.01, 0.01 ]
Favours placebo
(Continued . . . )
344
(. . .
Study or subgroup Corticosteroid (very potent) n/N Total events: 0 (Corticosteroid (very potent)), 0 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 2 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Total (95% CI)
1047
897
100.0 %
0.00 [ -0.01, 0.01 ]
Total events: 2 (Corticosteroid (very potent)), 3 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 1.36, df = 10 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.46 (P = 0.65)
-1
-0.5
0.5
Favours placebo
Analysis 3.8. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Placebo n/N
Weight
1 Amcinonide Ellis 1988 0/83 1/82 12.0 % -0.01 [ -0.05, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.72 (P = 0.47) 2 Clobetasol propionate Franz 2000 Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Lebwohl 2002
83
82
12.0 %
-0.01 [ -0.05, 0.02 ]
0/125 0/139 0/95 1/44 0/61
0/63 1/140 0/47 6/45 0/20

-1 -0.5 0 0.5 1
13.9 % 14.8 % 12.2 % 3.1 % 6.1 %
0.0 [ -0.02, 0.02 ] -0.01 [ -0.03, 0.01 ] 0.0 [ -0.03, 0.03 ] -0.11 [ -0.22, 0.00 ] 0.0 [ -0.07, 0.07 ]
Favours placebo
(Continued . . . )
345
(. . .
Study or subgroup Corticosteroid (very potent) n/N Olsen 1991 2/189 Placebo n/N 17/189 Risk Difference MH,Random,95% CI Weight
Continued)
Risk Difference MH,Random,95% CI -0.08 [ -0.12, -0.04 ]
9.9 %
Subtotal (95% CI)
653
504
59.9 %
-0.02 [ -0.06, 0.01 ]
Total events: 3 (Corticosteroid (very potent)), 24 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 30.80, df = 5 (P = 0.00001); I?? =84% Test for overall effect: Z = 1.27 (P = 0.21) 3 Halcinonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Halobetasol Bernhard 1991 (1) Bernhard 1991(2)
0.0 %
0.0 [ 0.0, 0.0 ]
0/100 0/72
0/100 0/72
14.8 % 13.3 %
0.0 [ -0.02, 0.02 ] 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)
172
172
28.1 %
0.0 [ -0.02, 0.02 ]
Total (95% CI)
908
758
100.0 %
-0.01 [ -0.04, 0.01 ]
Total events: 3 (Corticosteroid (very potent)), 25 (Placebo) Heterogeneity: Tau?? = 0.00; Chi?? = 32.51, df = 8 (P = 0.00008); I?? =75% Test for overall effect: Z = 1.28 (P = 0.20)
-1
-0.5
0.5
Favours placebo
346
Analysis 3.9. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 9 Adverse events (local).
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Placebo n/N
Weight
1 Amcinonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Clobetasol propionate Gottlieb 2003 Jarratt 2004 Jorizzo 1997 Lebwohl 2002 Olsen 1991
0.0 %
0.0 [ 0.0, 0.0 ]
7/139 13/94 5/44 17/61 21/189
10/140 10/47 5/45 6/20 18/189
8.5 % 1.4 % 1.5 % 0.5 % 7.1 %
-0.02 [ -0.08, 0.03 ] -0.07 [ -0.21, 0.06 ] 0.00 [ -0.13, 0.13 ] -0.02 [ -0.25, 0.21 ] 0.02 [ -0.05, 0.08 ]
Subtotal (95% CI)
527
441
19.1 %
-0.01 [ -0.05, 0.03 ]
Total events: 63 (Corticosteroid (very potent)), 49 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 1.74, df = 4 (P = 0.78); I?? =0.0% Test for overall effect: Z = 0.49 (P = 0.62) 3 Halcinonide Lepaw 1978 0/29 1/29 3.3 % -0.03 [ -0.12, 0.06 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.75 (P = 0.45) 4 Halobetasol Bernhard 1991 (1) Katz 1991b
29
29
3.3 %
-0.03 [ -0.12, 0.06 ]
0/100 7/110
0/100 7/110
71.2 % 6.4 %
0.0 [ -0.02, 0.02 ] 0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)
210
210
77.6 %
0.0 [ -0.02, 0.02 ]
Total (95% CI)
766
680
100.0 %
0.00 [ -0.02, 0.01 ]
-1
-0.5
0.5
Favours placebo
347
Analysis 3.10. Comparison 3 Corticosteroid (very potent) vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 3 Corticosteroid (very potent) vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Placebo n/N
Weight
1 Amcinonide
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Clobetasol propionate Gottlieb 2003 Lebwohl 2002 Olsen 1991
0.0 %
0.0 [ 0.0, 0.0 ]
0/139 17/61 4/83
1/140 6/20 4/85
25.0 % 0.2 % 2.3 %
-0.01 [ -0.03, 0.01 ] -0.02 [ -0.25, 0.21 ] 0.00 [ -0.06, 0.07 ]
Subtotal (95% CI)
283
245
27.5 %
-0.01 [ -0.03, 0.01 ]
Total events: 21 (Corticosteroid (very potent)), 11 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.08, df = 2 (P = 0.96); I?? =0.0% Test for overall effect: Z = 0.69 (P = 0.49) 3 Halcinonide Sudilovsky 1981 0/78 0/78 15.7 % 0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 4 Halobetasol Bernhard 1991 (1) Katz 1991b
78
78
15.7 %
0.0 [ -0.02, 0.02 ]
0/100 0/110
0/100 0/110
25.7 % 31.0 %
0.0 [ -0.02, 0.02 ] 0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)
210
210
56.7 %
0.0 [ -0.01, 0.01 ]
Total (95% CI)
571
533
100.0 %
0.00 [ -0.01, 0.01 ]
-1
-0.5
0.5
Favours placebo
348
Analysis 4.1. Comparison 4 Dithranol vs. placebo, Outcome 1 IAGI.

Comparison: 4 Dithranol vs. placebo Outcome: 1 IAGI
Study or subgroup
Dithranol N Mean(SD) -53.8 (29.1)
Placebo N 8 Mean(SD) -26.4 (13.8)
Weight
Buckley 1978
100.0 %
-1.14 [ -2.22, -0.06 ]
Total (95% CI)

100.0 %
-1.14 [ -2.22, -0.06 ]
-10
-5
10
Favours dithranol
Favours placebo
Analysis 4.2. Comparison 4 Dithranol vs. placebo, Outcome 2 TSS.

Comparison: 4 Dithranol vs. placebo Outcome: 2 TSS
Study or subgroup
Dithranol N Mean(SD) -0.54 (0.29) 1.2 (1.77) 0.99 (0.47)
Placebo N 8 12 27 Mean(SD) -0.26 (0.14) 4.1 (1.59) 1.3 (0.42)
Weight
Buckley 1978 Grattan 1997 (P) Jekler 1992
8 12 27
22.7 % 27.3 % 50.0 %
-1.16 [ -2.25, -0.08 ] -1.66 [ -2.62, -0.71 ] -0.69 [ -1.24, -0.14 ]
Total (95% CI)
47
47
100.0 %
-1.06 [ -1.66, -0.46 ]
Heterogeneity: Tau?? = 0.11; Chi?? = 3.19, df = 2 (P = 0.20); I?? =37% Test for overall effect: Z = 3.45 (P = 0.00056)
-10
-5
10
Favours dithranol
Favours placebo
349
Analysis 4.5. Comparison 4 Dithranol vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 4 Dithranol vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Dithranol N Mean(SD) -53.8 (29.1) 1.2 (1.77) 0.99 (0.47)
Placebo N 8 12 27 Mean(SD) -26.4 (13.8) 4.1 (1.59) 1.3 (0.42)
Weight
Buckley 1978 Grattan 1997 (P) Jekler 1992
8 12 27
22.7 % 27.2 % 50.1 %
-1.14 [ -2.22, -0.06 ] -1.66 [ -2.62, -0.71 ] -0.69 [ -1.24, -0.14 ]
Total (95% CI)
47
47
100.0 %
-1.05 [ -1.65, -0.46 ]
-10
-5
10
Favours dithranol
Favours placebo
Analysis 4.6. Comparison 4 Dithranol vs. placebo, Outcome 6 Total withdrawals.

Comparison: 4 Dithranol vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Dithranol n/N
Placebo n/N 2/10 0/12 3/30 1/10
Weight
Risk Difference MH,Random,95% CI 0.0 [ -0.35, 0.35 ] 0.0 [ -0.15, 0.15 ] 0.0 [ -0.15, 0.15 ] 0.0 [ -0.26, 0.26 ]
Buckley 1978 Grattan 1997 (P) Jekler 1992 Volden 1992
2/10 0/12 3/30 1/10
7.3 % 40.9 % 38.8 % 12.9 %
Total (95% CI)
62
62
100.0 %
0.0 [ -0.09, 0.09 ]
Total events: 6 (Dithranol), 6 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 3 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
-1
-0.5
0.5
Favours dithranol
Favours placebo
350
Analysis 4.7. Comparison 4 Dithranol vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 4 Dithranol vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Dithranol n/N
Placebo n/N 0/12 0/30 0/10
Weight
Grattan 1997 (P) Jekler 1992 Volden 1992
0/12 0/30 0/10
13.7 % 76.4 % 9.9 %
Total (95% CI)
52
52
100.0 %
0.0 [ -0.05, 0.05 ]
-1
-0.5
0.5
Favours dithranol
Favours placebo
Analysis 4.8. Comparison 4 Dithranol vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 4 Dithranol vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Dithranol n/N
Placebo n/N 0/12 0/10
Weight
Risk Difference MH,Random,95% CI 0.0 [ -0.15, 0.15 ] 0.0 [ -0.17, 0.17 ]
Grattan 1997 (P) Volden 1992
0/12 0/10
58.1 % 41.9 %
Total (95% CI)
22
22
100.0 %
0.0 [ -0.11, 0.11 ]
-1
-0.5
0.5
Favours dithranol
Favours placebo
351
Analysis 4.9. Comparison 4 Dithranol vs. placebo, Outcome 9 Adverse events (local).
Comparison: 4 Dithranol vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Dithranol n/N
Placebo n/N 2/7 0/30 0/10
Weight
Risk Difference MH,Random,95% CI 0.43 [ -0.04, 0.90 ] 0.0 [ -0.06, 0.06 ] 0.40 [ 0.08, 0.72 ]
Buckley 1978 Jekler 1992 Volden 1992
5/7 0/30 4/10
29.5 % 37.1 % 33.4 %
Total (95% CI)
47
47
100.0 %
0.26 [ -0.30, 0.82 ]
Total events: 9 (Dithranol), 2 (Placebo) Heterogeneity: Tau?? = 0.22; Chi?? = 25.44, df = 2 (P<0.00001); I?? =92% Test for overall effect: Z = 0.91 (P = 0.36)
-2
-1
Favours dithranol
Favours placebo
Analysis 4.10. Comparison 4 Dithranol vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 4 Dithranol vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Dithranol n/N
Placebo n/N 2/10
Weight
Buckley 1978
2/10
100.0 %
Total (95% CI)

10
10
100.0 %
0.0 [ -0.35, 0.35 ]
Total events: 2 (Dithranol), 2 (Placebo) Test for overall effect: Z = 0.0 (P = 1.0)
-2
-1
Favours dithranol
Favours placebo
352
Analysis 5.2. Comparison 5 Tazarotene vs. placebo, Outcome 2 TSS.

Comparison: 5 Tazarotene vs. placebo Outcome: 2 TSS
Study or subgroup
Tazarotene N Mean(SD) 3.8 (1.64)
Placebo N 107 Mean(SD) 5.3 (1.64)
Weight
Weinstein 1996
211
100.0 %
-0.91 [ -1.16, -0.67 ]
Total (95% CI)

211
107
100.0 %
-0.91 [ -1.16, -0.67 ]
-10
-5
10
Favours tazarotene
Favours placebo
Analysis 5.5. Comparison 5 Tazarotene vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 5 Tazarotene vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Tazarotene N Mean(SD) 3.8 (1.64)
Placebo N 107 Mean(SD) 5.3 (1.64)
Weight
Weinstein 1996
211
100.0 %
-0.91 [ -1.16, -0.67 ]
Total (95% CI)

211
107
100.0 %
-0.91 [ -1.16, -0.67 ]
-10
-5
10
Favours tazarotene
Favours placebo
353
Analysis 5.6. Comparison 5 Tazarotene vs. placebo, Outcome 6 Total withdrawals.

Comparison: 5 Tazarotene vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Tazarotene n/N
Placebo n/N 27/108 125/443
Weight
Risk Difference MH,Random,95% CI 0.00 [ -0.10, 0.10 ] 0.05 [ 0.00, 0.10 ]
Weinstein 1996 Weinstein 2003
55/216 286/860
21.5 % 78.5 %
Total (95% CI)
1076
551
100.0 %
0.04 [ -0.01, 0.09 ]
Total events: 341 (Tazarotene), 152 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.63, df = 1 (P = 0.43); I?? =0.0% Test for overall effect: Z = 1.71 (P = 0.087)
-1
-0.5
0.5
Favours tazarotene
Favours placebo
Analysis 5.7. Comparison 5 Tazarotene vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 5 Tazarotene vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Tazarotene n/N
Placebo n/N 3/108 20/443
Weight
Risk Difference MH,Random,95% CI 0.08 [ 0.03, 0.14 ] 0.07 [ 0.04, 0.10 ]
24/216 97/860
23.2 % 76.8 %
Total (95% CI)
1076
551
100.0 %
0.07 [ 0.05, 0.10 ]
Total events: 121 (Tazarotene), 23 (Placebo) Heterogeneity: Tau?? = 0.0; Chi?? = 0.27, df = 1 (P = 0.60); I?? =0.0% Test for overall effect: Z = 5.56 (P < 0.00001)
-1
-0.5
0.5
Favours tazarotene
Favours placebo
354
Analysis 5.8. Comparison 5 Tazarotene vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 5 Tazarotene vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Tazarotene n/N
Placebo n/N 6/108 28/443
Weight
Risk Difference MH,Random,95% CI -0.01 [ -0.06, 0.04 ] -0.02 [ -0.04, 0.01 ]
9/216 40/860
21.6 % 78.4 %
Total (95% CI)
1076
551
100.0 %
-0.02 [ -0.04, 0.01 ]
-1
-0.5
0.5
Favours tazarotene
Favours placebo
Analysis 5.9. Comparison 5 Tazarotene vs. placebo, Outcome 9 Adverse events (local).
Comparison: 5 Tazarotene vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Tazarotene n/N
Placebo n/N 0/10
Weight
Risk Difference MH,Random,95% CI 0.24 [ 0.02, 0.46 ]
Scher 2001
5/21
100.0 %
Total (95% CI)

21
10
100.0 %
0.24 [ 0.02, 0.46 ]
Total events: 5 (Tazarotene), 0 (Placebo) Test for overall effect: Z = 2.13 (P = 0.033)
-2
-1
Favours tazarotene
Favours placebo
355
Analysis 5.10. Comparison 5 Tazarotene vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 5 Tazarotene vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Tazarotene n/N
Placebo n/N 0/45 0/108
Weight
Krueger 1998 Weinstein 1996
0/45 0/216
10.1 % 89.9 %
Total (95% CI)
261
153
100.0 %
0.0 [ -0.01, 0.01 ]
-0.5
-0.25
0.25
0.5
Favours tazarotene
Favours placebo
356
Analysis 6.1. Comparison 6 Other treatment vs. placebo, Outcome 1 IAGI.

Comparison: 6 Other treatment vs. placebo Outcome: 1 IAGI
Study or subgroup
Other treatment N Mean(SD)
Placebo N Mean(SD)
Weight
1 Aloe vera extract
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Anti IL-8 monoclonal antibody cream Jin 2001
0.0 %
0.0 [ 0.0, 0.0 ]
45
-1.27 (1.01)
44
-0.73 (0.79)
100.0 %
-0.59 [ -1.01, -0.16 ]
Subtotal (95% CI)

45
44
100.0 % -0.59 [ -1.01, -0.16 ]
Test for overall effect: Z = 2.72 (P = 0.0065) 3 Betamethasone-17,21-dipropionate plus salicylic acid Elie 1983 10 -2.55 (1) 10 -0.8 (1) 100.0 % -1.68 [ -2.73, -0.63 ]
Subtotal (95% CI)

10
10
100.0 % -1.68 [ -2.73, -0.63 ]
Test for overall effect: Z = 3.13 (P = 0.0018) 4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid Santoianni 2001 42 -2.36 (0.69) 39 -1.79 (0.8) 100.0 % -0.76 [ -1.21, -0.31 ]
Subtotal (95% CI)

42
39
100.0 % -0.76 [ -1.21, -0.31 ]
Test for overall effect: Z = 3.29 (P = 0.0010) 5 Ciclopirox olamine shampoo
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Ciclosporin solution in oil
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Dead Sea salts emollient lotion
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Fish oil plus occlusion
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours other treatment
Favours placebo
(Continued . . . )
357
(. . .
Study or subgroup Other treatment N Test for overall effect: not applicable 9 Hexauoro-1,25-dihydroxyvitamin D3 Durakovic 2001 15 -3.3 (0.71) 15 -2.8 (0.86) 100.0 % Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
-0.62 [ -1.35, 0.12 ]
Subtotal (95% CI)

15
15
100.0 %
-0.62 [ -1.35, 0.12 ]
Test for overall effect: Z = 1.65 (P = 0.10) 10 Methotrexate gel Sutton 2001 39 -2.34 (1.2) 41 -1.78 (0.72) 100.0 % -0.56 [ -1.01, -0.12 ]
Subtotal (95% CI)

39
41
100.0 % -0.56 [ -1.01, -0.12 ]
Test for overall effect: Z = 2.47 (P = 0.014) 11 Mycophenolic acid ointment
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
12 NG-monomethyl-L-arginine (L-NMMA) cream
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 13 Oleum horwathiensis (Psoricur??) Lassus 1991
0.0 %
0.0 [ 0.0, 0.0 ]
19
-2.21 (1.69)
23
-2.17 (1.72)
100.0 %
-0.02 [ -0.63, 0.58 ]
Subtotal (95% CI)

19
23
100.0 %
-0.02 [ -0.63, 0.58 ]
Test for overall effect: Z = 0.07 (P = 0.94) 14 Omega-3-polyunsaturated fatty acids ointment
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 15 Pimecrolimus cream, 1% BD Gribetz 2004
0.0 %
0.0 [ 0.0, 0.0 ]
22
-2.95 (1.33)
25
-1.56 (1.23)
100.0 %
-1.07 [ -1.69, -0.45 ]
Subtotal (95% CI)

22
25
100.0 % -1.07 [ -1.69, -0.45 ]
Test for overall effect: Z = 3.40 (P = 0.00066) 16 Platelet aggregation activating factor (PAF)(Ro 24-0238) Wolska 1995 40 -3.13 (0.79) 40 -3.08 (0.73) 100.0 % -0.07 [ -0.50, 0.37 ]
Subtotal (95% CI)

40
40
100.0 %
-0.07 [ -0.50, 0.37 ]
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment N 17 Polymyxin B cream, 200,000U/g Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
18 PTH (1-34) in Novasome A?? liposomal cream, BD
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 19 Salicylic acid Elie 1983
0.0 %
0.0 [ 0.0, 0.0 ]
10
-1.8 (1)
10
-0.8 (1)
100.0 %
-0.96 [ -1.89, -0.02 ]
Subtotal (95% CI)

10
10
100.0 % -0.96 [ -1.89, -0.02 ]
Test for overall effect: Z = 2.00 (P = 0.045) 20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 21 Tacrolimus ointment
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 22 Tar Kanzler 1993
0.0 %
0.0 [ 0.0, 0.0 ]
18
-48.7 (28.4)
18
-35.3 (26)
100.0 %
-0.48 [ -1.15, 0.18 ]
Subtotal (95% CI)

18
18
100.0 %
-0.48 [ -1.15, 0.18 ]
-10
-5
10
Favours placebo
359
Analysis 6.2. Comparison 6 Other treatment vs. placebo, Outcome 2 TSS.

Comparison: 6 Other treatment vs. placebo Outcome: 2 TSS
Study or subgroup
Placebo N Mean(SD)
Weight
1 Aloe vera extract
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Anti IL-8 monoclonal antibody cream Jin 2001
0.0 %
0.0 [ 0.0, 0.0 ]
45
4.78 (3.2)
44
7.09 (3.31)
100.0 %
-0.70 [ -1.13, -0.27 ]
Subtotal (95% CI)

45
44
100.0 % -0.70 [ -1.13, -0.27 ]
Test for overall effect: Z = 3.22 (P = 0.0013) 3 Betamethasone-17,21-dipropionate plus salicylic acid Elie 1983 10 1.15 (2.74) 10 3.87 (2.74) 100.0 % -0.95 [ -1.89, -0.01 ]
Subtotal (95% CI)

10
10
100.0 % -0.95 [ -1.89, -0.01 ]
Test for overall effect: Z = 1.99 (P = 0.047) 4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Ciclopirox olamine shampoo Shuttleworth 1998
0.0 %
0.0 [ 0.0, 0.0 ]
28
4.25 (2.49)
4.44 (2.65)
100.0 %
-0.07 [ -0.82, 0.68 ]
Subtotal (95% CI)

28
100.0 %
-0.07 [ -0.82, 0.68 ]
Test for overall effect: Z = 0.19 (P = 0.85) 6 Ciclosporin solution in oil Cannavo 2003 8 2.13 (1.81) 8 4.88 (2.36) 100.0 % -1.24 [ -2.33, -0.14 ]
Subtotal (95% CI)

100.0 % -1.24 [ -2.33, -0.14 ]
Test for overall effect: Z = 2.21 (P = 0.027) 7 Dead Sea salts emollient lotion
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
360
(. . .
Study or subgroup Other treatment N Escobar 1992 25 Mean(SD) 1.74 (1.91) Placebo N 25 Mean(SD) 3.81 (1.91) Std. Mean Difference IV,Random,95% CI 100.0 % Weight
IV,Random,95% CI -1.07 [ -1.66, -0.47 ]
Subtotal (95% CI)

25
25
100.0 % -1.07 [ -1.66, -0.47 ]
Test for overall effect: Z = 3.51 (P = 0.00045) 9 Hexauoro-1,25-dihydroxyvitamin D3, BD Durakovic 2001 15 2.4 (4.9) 15 8.1 (4.9) 100.0 % -1.13 [ -1.91, -0.35 ]
Subtotal (95% CI)

15
15
100.0 % -1.13 [ -1.91, -0.35 ]
Test for overall effect: Z = 2.85 (P = 0.0044) 10 Methotrexate gel Sutton 2001 41 -2.98 (3.93) 41 -1.32 (2.77) 100.0 % -0.48 [ -0.92, -0.04 ]
Subtotal (95% CI)

41
41
100.0 % -0.48 [ -0.92, -0.04 ]
Test for overall effect: Z = 2.16 (P = 0.031) 11 Mycophenolic acid ointment Geilen 2000 7 5.13 (0.73) 7 6.32 (0.81) 100.0 % -1.44 [ -2.67, -0.22 ]
Subtotal (95% CI)

100.0 % -1.44 [ -2.67, -0.22 ]
Test for overall effect: Z = 2.32 (P = 0.021) 12 NG-monomethyl-L-arginine (L-NMMA) cream Ormerod 2000 17 9.12 (3.55) 17 8.82 (4.22) 100.0 % 0.08 [ -0.60, 0.75 ]
Subtotal (95% CI)

17
17
100.0 %
0.08 [ -0.60, 0.75 ]
Test for overall effect: Z = 0.22 (P = 0.83) 13 Oleum horwathiensis (Psoricur??) Lassus 1991 19 -0.74 (0.23) 23 -0.56 (0.23) 100.0 % -0.77 [ -1.40, -0.14 ]
Subtotal (95% CI)

19
23
100.0 % -0.77 [ -1.40, -0.14 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
28
-4.1 (1.1)
29
-2.67 (1.1)
100.0 %
-1.28 [ -1.86, -0.71 ]
Subtotal (95% CI)

28
29
100.0 % -1.28 [ -1.86, -0.71 ]
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment N Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
16 Platelet aggregation activating factor (PAF)(Ro 24-0238)
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 17 Polymyxin B cream, 200,000U/g Stutz 1996
0.0 %
0.0 [ 0.0, 0.0 ]
15
2.5 (1.5)
15
2.3 (1.5)
100.0 %
0.13 [ -0.59, 0.85 ]
Subtotal (95% CI)

15
15
100.0 %
0.13 [ -0.59, 0.85 ]
Test for overall effect: Z = 0.35 (P = 0.72) 18 PTH (1-34) in Novasome A?? liposomal cream, BD Holick 2003 15 -0.67 (0.23) 15 -0.18 (0.18) 100.0 % -2.31 [ -3.26, -1.36 ]
Subtotal (95% CI)

15
15
100.0 % -2.31 [ -3.26, -1.36 ]
Test for overall effect: Z = 4.76 (P < 0.00001) 19 Salicylic acid Elie 1983 10 2.18 (2.74) 10 3.87 (2.74) 100.0 % -0.59 [ -1.49, 0.31 ]
Subtotal (95% CI)

10
10
100.0 %
-0.59 [ -1.49, 0.31 ]
Test for overall effect: Z = 1.29 (P = 0.20) 20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks Ormerod 2005 22 9.1 (4.8) 22 11.2 (5.8) 100.0 % -0.39 [ -0.98, 0.21 ]
Subtotal (95% CI)

22
22
100.0 %
-0.39 [ -0.98, 0.21 ]
Test for overall effect: Z = 1.27 (P = 0.20) 21 Tacrolimus ointment Zonneveld 1998 (P) 24 4.7 (1.64) 23 4.6 (1.64) 100.0 % 0.06 [ -0.51, 0.63 ]
Subtotal (95% CI)

24
23
100.0 %
0.06 [ -0.51, 0.63 ]
Test for overall effect: Z = 0.21 (P = 0.84) 22 Tar Kanzler 1993 18 -3.25 (2.03) 18 -2.36 (1.86) 100.0 % -0.45 [ -1.11, 0.22 ]
Subtotal (95% CI)

18
18
100.0 %
-0.45 [ -1.11, 0.22 ]
-10
-5
10
Favours placebo
362
Analysis 6.3. Comparison 6 Other treatment vs. placebo, Outcome 3 PASI.

Comparison: 6 Other treatment vs. placebo Outcome: 3 PASI
Study or subgroup
Placebo N Mean(SD)
Weight
1 Aloe vera extract Syed 1996 30 2.2 (3.66) 30 8.2 (3.66) 100.0 % -1.62 [ -2.21, -1.03 ]
Subtotal (95% CI)

30
30
100.0 % -1.62 [ -2.21, -1.03 ]
Test for overall effect: Z = 5.39 (P < 0.00001) 2 Anti IL-8 monoclonal antibody cream
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
3 Betamethasone-17,21-dipropionate plus salicylic acid
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid Santoianni 2001 42 2.28 (3.03) 39 3.94 (3.03) 100.0 % -0.54 [ -0.99, -0.10 ]
Subtotal (95% CI)

42
39
100.0 % -0.54 [ -0.99, -0.10 ]
Test for overall effect: Z = 2.39 (P = 0.017) 5 Ciclopirox olamine shampoo
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Ciclosporin solution in oil
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Dead Sea salts emollient lotion, 30% Cheesbrough 1992
0.0 %
0.0 [ 0.0, 0.0 ]
24 (11.1)
11
18.5 (7.5)
100.0 %
0.57 [ -0.36, 1.51 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.20 (P = 0.23) 8 Fish oil plus occlusion
11
100.0 %
0.57 [ -0.36, 1.51 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
363
(. . .
Study or subgroup Other treatment N Test for overall effect: not applicable 9 Hexauoro-1,25-dihydroxyvitamin D3, BD Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 10 Methotrexate gel Syed 2001b
0.0 %
0.0 [ 0.0, 0.0 ]
30
2.2 (3.66)
30
8.2 (3.66)
100.0 %
-1.62 [ -2.21, -1.03 ]
Subtotal (95% CI)

30
30
100.0 % -1.62 [ -2.21, -1.03 ]
Test for overall effect: Z = 5.39 (P < 0.00001) 11 Mycophenolic acid ointment
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 13 Oleum horwathiensis (Psoricur??)
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
14 Omega-3-polyunsaturated fatty acids ointment
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 15 Pimecrolimus cream, 1% BD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 17 Polymyxin B cream, 200,000U/g
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 19 Salicylic acid
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 22 Tar
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
365
Analysis 6.4. Comparison 6 Other treatment vs. placebo, Outcome 4 PAGI.

Comparison: 6 Other treatment vs. placebo Outcome: 4 PAGI
Study or subgroup
Placebo N Mean(SD)
Weight
1 Aloe vera extract
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Anti IL-8 monoclonal antibody cream
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid Santoianni 2001 42 -2.55 (0.99) 39 -1.69 (1.13) 100.0 % -0.80 [ -1.26, -0.35 ]
Subtotal (95% CI)

42
39
100.0 % -0.80 [ -1.26, -0.35 ]
Test for overall effect: Z = 3.47 (P = 0.00052) 5 Ciclopirox olamine shampoo Shuttleworth 1998 28 -2 (1) 9 -1.89 (0.93) 100.0 % -0.11 [ -0.86, 0.64 ]
Subtotal (95% CI)

28
100.0 %
-0.11 [ -0.86, 0.64 ]
Test for overall effect: Z = 0.29 (P = 0.78) 6 Ciclosporin solution in oil Cannavo 2003 8 -3 (0.53) 8 -1.13 (0.35) 100.0 % -3.94 [ -5.79, -2.09 ]
Subtotal (95% CI)

100.0 % -3.94 [ -5.79, -2.09 ]
Test for overall effect: Z = 4.17 (P = 0.000031) 7 Dead Sea salts emollient lotion, 30%
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
366
(. . .
Study or subgroup Other treatment N Test for overall effect: not applicable 9 Hexauoro-1,25-dihydroxyvitamin D3, BD Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 10 Methotrexate gel
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 11 Mycophenolic acid ointment
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 13 Oleum horwathiensis (Psoricur??)
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
22
-2.36 (0.85)
25
-1.72 (1.06)
100.0 %
-0.65 [ -1.24, -0.06 ]
Subtotal (95% CI)

22
25
100.0 % -0.65 [ -1.24, -0.06 ]
Test for overall effect: Z = 2.16 (P = 0.031) 16 Platelet aggregation activating factor (PAF)(Ro 24-0238)
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 17 Polymyxin B cream, 200,000U/g
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 19 Salicylic acid
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 22 Tar
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
368
Analysis 6.5. Comparison 6 Other treatment vs. placebo, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 6 Other treatment vs. placebo Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Placebo N Mean(SD)
Weight
1 Aloe vera extract Syed 1996 30 2.2 (3.66) 30 8.2 (3.66) 100.0 % -1.62 [ -2.21, -1.03 ]
Subtotal (95% CI)

30
30
100.0 % -1.62 [ -2.21, -1.03 ]
Test for overall effect: Z = 5.39 (P < 0.00001) 2 Anti IL-8 monoclonal antibody cream Jin 2001 45 -1.27 (1.01) 44 -0.73 (0.79) 100.0 % -0.59 [ -1.01, -0.16 ]
Subtotal (95% CI)

45
44
100.0 % -0.59 [ -1.01, -0.16 ]
Test for overall effect: Z = 2.72 (P = 0.0065) 3 Betamethasone-17,21-dipropionate plus salicylic acid Elie 1983 10 -2.55 (1) 10 -0.8 (1) 100.0 % -1.68 [ -2.73, -0.63 ]
Subtotal (95% CI)

10
10
100.0 % -1.68 [ -2.73, -0.63 ]
Test for overall effect: Z = 3.13 (P = 0.0018) 4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid Santoianni 2001 42 -2.36 (0.69) 39 -1.79 (0.8) 100.0 % -0.76 [ -1.21, -0.31 ]
Subtotal (95% CI)

42
39
100.0 % -0.76 [ -1.21, -0.31 ]
Test for overall effect: Z = 3.29 (P = 0.0010) 5 Ciclopirox olamine shampoo Shuttleworth 1998 28 4.25 (2.49) 9 4.44 (2.65) 100.0 % -0.07 [ -0.82, 0.68 ]
Subtotal (95% CI)

28
100.0 %
-0.07 [ -0.82, 0.68 ]
Test for overall effect: Z = 0.19 (P = 0.85) 6 Ciclosporin solution in oil Cannavo 2003 8 2.13 (1.81) 8 4.88 (2.36) 100.0 % -1.24 [ -2.33, -0.14 ]
Subtotal (95% CI)

100.0 % -1.24 [ -2.33, -0.14 ]
Test for overall effect: Z = 2.21 (P = 0.027) 7 Dead Sea salts emollient lotion, 30%
-10
-5
10
Favours placebo
(Continued . . . )
369
(. . .
Study or subgroup Other treatment N Cheesbrough 1992 8 Mean(SD) 24 (11.1) Placebo N 11 Mean(SD) 18.5 (7.5) Std. Mean Difference IV,Random,95% CI 100.0 % Weight
IV,Random,95% CI 0.57 [ -0.36, 1.51 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.20 (P = 0.23) 8 Fish oil plus occlusion Escobar 1992
11
100.0 %
0.57 [ -0.36, 1.51 ]
25
1.74 (1.91)
25
3.81 (1.91)
100.0 %
-1.07 [ -1.66, -0.47 ]
Subtotal (95% CI)

25
25
100.0 % -1.07 [ -1.66, -0.47 ]
Test for overall effect: Z = 3.51 (P = 0.00045) 9 Hexauoro-1,25-dihydroxyvitamin D3 Durakovic 2001 15 -3.3 (0.71) 15 -2.8 (0.86) 100.0 % -0.62 [ -1.35, 0.12 ]
Subtotal (95% CI)

15
15
100.0 %
-0.62 [ -1.35, 0.12 ]
Test for overall effect: Z = 1.65 (P = 0.10) 10 Methotrexate gel Sutton 2001 Syed 2001b 39 30 -2.34 (1.2) 2.2 (3.66) 41 30 -1.78 (0.72) 8.2 (3.66) 52.7 % 47.3 % -0.56 [ -1.01, -0.12 ] -1.62 [ -2.21, -1.03 ]
Subtotal (95% CI)
69
71
100.0 % -1.07 [ -2.11, -0.04 ]
Heterogeneity: Tau?? = 0.48; Chi?? = 7.82, df = 1 (P = 0.01); I?? =87% Test for overall effect: Z = 2.04 (P = 0.042) 11 Mycophenolic acid ointment Geilen 2000 7 5.13 (0.73) 7 6.32 (0.81) 100.0 % -1.44 [ -2.67, -0.22 ]
Subtotal (95% CI)

100.0 % -1.44 [ -2.67, -0.22 ]
Test for overall effect: Z = 2.32 (P = 0.021) 12 NG-monomethyl-L-arginine (L-NMMA) cream Ormerod 2000 17 9.12 (3.55) 17 8.82 (4.22) 100.0 % 0.08 [ -0.60, 0.75 ]
Subtotal (95% CI)

17
17
100.0 %
0.08 [ -0.60, 0.75 ]
Test for overall effect: Z = 0.22 (P = 0.83) 13 Oleum horwathiensis (Psoricur??) Lassus 1991 19 -2.21 (1.69) 23 -2.17 (1.72) 100.0 % -0.02 [ -0.63, 0.58 ]
Subtotal (95% CI)

19
23
100.0 %
-0.02 [ -0.63, 0.58 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment N Test for overall effect: not applicable 15 Pimecrolimus cream, 1% BD Gribetz 2004 22 -2.95 (1.33) 25 -1.56 (1.23) 100.0 % Mean(SD) Placebo N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
-1.07 [ -1.69, -0.45 ]
Subtotal (95% CI)

22
25
100.0 % -1.07 [ -1.69, -0.45 ]
Test for overall effect: Z = 3.40 (P = 0.00066) 16 Platelet aggregation activating factor (PAF)(Ro 24-0238) Wolska 1995 40 -3.13 (0.79) 40 -3.08 (0.73) 100.0 % -0.07 [ -0.50, 0.37 ]
Subtotal (95% CI)

40
40
100.0 %
-0.07 [ -0.50, 0.37 ]
Test for overall effect: Z = 0.29 (P = 0.77) 17 Polymyxin B cream, 200,000U/g Stutz 1996 15 2.5 (1.5) 15 2.3 (1.5) 100.0 % 0.13 [ -0.59, 0.85 ]
Subtotal (95% CI)

15
15
100.0 %
0.13 [ -0.59, 0.85 ]
Test for overall effect: Z = 0.35 (P = 0.72) 18 PTH (1-34) in Novasome A?? liposomal cream, BD Holick 2003 15 -0.67 (0.23) 15 -0.18 (0.18) 100.0 % -2.31 [ -3.26, -1.36 ]
Subtotal (95% CI)

15
15
100.0 % -2.31 [ -3.26, -1.36 ]
Test for overall effect: Z = 4.76 (P < 0.00001) 19 Salicylic acid Elie 1983 10 -1.8 (1) 10 -0.8 (1) 100.0 % -0.96 [ -1.89, -0.02 ]
Subtotal (95% CI)

10
10
100.0 % -0.96 [ -1.89, -0.02 ]
Test for overall effect: Z = 2.00 (P = 0.045) 20 Sirolimus (topical), 2.2% for 6 wks, then 8% for a further 6 wks Ormerod 2005 22 9.1 (4.8) 22 11.2 (5.8) 100.0 % -0.39 [ -0.98, 0.21 ]
Subtotal (95% CI)

22
22
100.0 %
-0.39 [ -0.98, 0.21 ]
Test for overall effect: Z = 1.27 (P = 0.20) 21 Tacrolimus ointment Zonneveld 1998 (P) 24 4.7 (1.64) 23 4.6 (1.64) 100.0 % 0.06 [ -0.51, 0.63 ]
Subtotal (95% CI)

24
23
100.0 %
0.06 [ -0.51, 0.63 ]
Test for overall effect: Z = 0.21 (P = 0.84) 22 Tar
-10
-5
10
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment N Kanzler 1993 18 Mean(SD) -48.7 (28.4) Placebo N 18 Mean(SD) -35.3 (26) Std. Mean Difference IV,Random,95% CI 100.0 % Weight
IV,Random,95% CI -0.48 [ -1.15, 0.18 ]
Subtotal (95% CI)

18
18
100.0 %
-0.48 [ -1.15, 0.18 ]
-10
-5
10
Favours placebo
Analysis 6.6. Comparison 6 Other treatment vs. placebo, Outcome 6 Total withdrawals.
Comparison: 6 Other treatment vs. placebo Outcome: 6 Total withdrawals
Study or subgroup
Other treatment n/N
Placebo n/N
Weight
1 Aloe vera extract Syed 1996 0/30 0/30 100.0 % 0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Anti IL-8 monoclonal antibody cream Jin 2001
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
3/48
4/48
100.0 %
-0.02 [ -0.12, 0.08 ]
Subtotal (95% CI)

Total events: 3 (Other treatment), 4 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.39 (P = 0.69)
48
48
100.0 %
-0.02 [ -0.12, 0.08 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable
0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
372
(. . .
Study or subgroup Other treatment n/N Santoianni 2001 2/44 Placebo n/N 2/41 Risk Difference MH,Random,95% CI Weight
Continued)
4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid 100.0 %
Subtotal (95% CI)

Total events: 2 (Other treatment), 2 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.07 (P = 0.94) 5 Ciclopirox olamine shampoo Shuttleworth 1998
44
41
100.0 %
0.00 [ -0.09, 0.09 ]
1/29
2/11
100.0 %
-0.15 [ -0.38, 0.09 ]
Subtotal (95% CI)

Total events: 1 (Other treatment), 2 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 1.22 (P = 0.22) 6 Ciclosporin solution in oil Cannavo 2003
29
11
100.0 %
-0.15 [ -0.38, 0.09 ]
0/8
0/8
100.0 %
0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 7 Dead Sea salts emollient lotion Cheesbrough 1992
100.0 %
0.0 [ -0.21, 0.21 ]
4/12
1/12
100.0 %
0.25 [ -0.06, 0.56 ]
Subtotal (95% CI)

Total events: 4 (Other treatment), 1 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 1.58 (P = 0.11) 8 Fish oil plus occlusion Escobar 1992
12
12
100.0 %
0.25 [ -0.06, 0.56 ]
0/25
0/25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 9 Hexauoro-1,25-dihydroxyvitamin D3 Durakovic 2001
25
25
100.0 %
0.0 [ -0.07, 0.07 ]
0/15
0/15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 10 Methotrexate gel Syed 2001b
15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/30
0/30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo)
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 11 Mycophenolic acid ointment Geilen 2000 0/7 0/7 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

100.0 %
0.0 [ -0.24, 0.24 ]
12 NG-monomethyl-L-arginine (L-NMMA) cream Ormerod 2000 0/17 0/17 100.0 % 0.0 [ -0.11, 0.11 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 13 Oleum horwathiensis Lassus 1991
17
17
100.0 %
0.0 [ -0.11, 0.11 ]
6/25
2/25
100.0 %
0.16 [ -0.04, 0.36 ]
Subtotal (95% CI)

25
25
100.0 %
0.16 [ -0.04, 0.36 ]
14 Omega-3-polyunsaturated fatty acids ointment Henneicke-v. Z. 1993 21/73 21/73 100.0 % 0.0 [ -0.15, 0.15 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 15 Pimecrolimus cream, 1% BD Gribetz 2004
73
73
100.0 %
0.0 [ -0.15, 0.15 ]
2/28
4/29
100.0 %
-0.07 [ -0.22, 0.09 ]
Subtotal (95% CI)

28
29
100.0 %
-0.07 [ -0.22, 0.09 ]
16 Platelet aggregation activating factor (PAF)(Ro 24-0238) Wolska 1995 12/52 12/52 100.0 % 0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

52
52
100.0 %
0.0 [ -0.16, 0.16 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N 17 Polymyxin B cream, 200,000U/g Stutz 1996 2/15 2/15 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

15
15
100.0 %
0.0 [ -0.24, 0.24 ]
18 PTH (1-34) in Novasome A?? liposomal cream, BD Holick 2003 0/15 0/15 100.0 % 0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 19 Salicylic acid
15
15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 20 Sirolimus (topical)
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 21 Tacrolimus ointment Lebwohl 2004
0.0 %
0.0 [ 0.0, 0.0 ]
14/112
16/55
100.0 %
-0.17 [ -0.30, -0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 2.41 (P = 0.016) 22 Tar
112
55
100.0 %
-0.17 [ -0.30, -0.03 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
375
Analysis 6.7. Comparison 6 Other treatment vs. placebo, Outcome 7 Withdrawals due to adverse events.
Comparison: 6 Other treatment vs. placebo Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Other treatment n/N
Placebo n/N
Weight
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Anti IL-8 monoclonal antibody cream
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
3 Betamethasone-17,21-dipropionate plus salicylic acid Elie 1983 0/10 0/10 100.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

10
10
100.0 %
0.0 [ -0.17, 0.17 ]
4 Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid Santoianni 2001 1/44 1/41 100.0 % 0.00 [ -0.07, 0.06 ]
Subtotal (95% CI)

44
41
100.0 %
0.00 [ -0.07, 0.06 ]
0/29
2/11
100.0 %
-0.18 [ -0.42, 0.05 ]
Subtotal (95% CI)

29
11
100.0 %
-0.18 [ -0.42, 0.05 ]
0/8
0/8
100.0 %
0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

100.0 %
0.0 [ -0.21, 0.21 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
376
(. . .
Study or subgroup Other treatment n/N Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 7 Dead Sea salts emollient lotion Cheesbrough 1992 2/12 1/12 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.08 [ -0.18, 0.35 ]
Subtotal (95% CI)

12
12
100.0 %
0.08 [ -0.18, 0.35 ]
0/25
0/25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

25
25
100.0 %
0.0 [ -0.07, 0.07 ]
0/15
0/15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/30
0/30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 11 Mycophenolic acid ointment Geilen 2000
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
0/7
0/7
100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 13 Oleum horwathiensis
17
17
100.0 %
0.0 [ -0.11, 0.11 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Lassus 1991 0/25 Placebo n/N 0/25 Risk Difference MH,Random,95% CI Weight
Continued)
100.0 %
Subtotal (95% CI)

25
25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 15 Pimecrolimus cream, 1% BD Gribetz 2004
73
73
100.0 %
0.0 [ -0.03, 0.03 ]
0/28
0/29
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

28
29
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 17 Polymyxin B cream, 200,000U/g
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 19 Salicylic acid Elie 1983
15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/10
0/10
100.0 %
0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

10
10
100.0 %
0.0 [ -0.17, 0.17 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N 20 Sirolimus (topical) Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/112
1/55
100.0 %
-0.02 [ -0.06, 0.03 ]
Subtotal (95% CI)

112
55
100.0 %
-0.02 [ -0.06, 0.03 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
379
Analysis 6.8. Comparison 6 Other treatment vs. placebo, Outcome 8 Withdrawals due to treatment failure.
Comparison: 6 Other treatment vs. placebo Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Other treatment n/N
Placebo n/N
Weight
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Anti IL-8 monoclonal antibody cream
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

44
41
100.0 %
0.02 [ -0.04, 0.08 ]
0/29
1/11
100.0 %
-0.09 [ -0.28, 0.10 ]
Subtotal (95% CI)

29
11
100.0 %
-0.09 [ -0.28, 0.10 ]
0/8
0/8
100.0 %
0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable
100.0 %
0.0 [ -0.21, 0.21 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
380
(. . .
Study or subgroup Other treatment n/N Test for overall effect: Z = 0.0 (P = 1.0) 7 Dead Sea salts emollient lotion Cheesbrough 1992 1/12 0/12 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.08 [ -0.12, 0.29 ]
Subtotal (95% CI)

12
12
100.0 %
0.08 [ -0.12, 0.29 ]
0/25
0/25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

25
25
100.0 %
0.0 [ -0.07, 0.07 ]
0/15
0/15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/30
0/30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
100.0 %
0.0 [ -0.06, 0.06 ]
0/7
0/7
100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

17
17
100.0 %
0.0 [ -0.11, 0.11 ]
0/25
0/25
-1 -0.5 0 0.5 1
100.0 %
0.0 [ -0.07, 0.07 ]
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

25
25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

73
73
100.0 %
0.0 [ -0.03, 0.03 ]
1/28
2/29
100.0 %
-0.03 [ -0.15, 0.08 ]
Subtotal (95% CI)

28
29
100.0 %
-0.03 [ -0.15, 0.08 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 17 Polymyxin B cream, 200,000U/g
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

15
15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)
0
-1 -0.5 0 0.5 1
0.0 %
0.0 [ 0.0, 0.0 ]
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 21 Tacrolimus ointment Lebwohl 2004 0/112 6/55 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
-0.11 [ -0.19, -0.02 ]
Subtotal (95% CI)

112
55
100.0 %
-0.11 [ -0.19, -0.02 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
383
Analysis 6.9. Comparison 6 Other treatment vs. placebo, Outcome 9 Adverse events (local).
Comparison: 6 Other treatment vs. placebo Outcome: 9 Adverse events (local)
Study or subgroup
Other treatment n/N
Placebo n/N
Weight
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Anti IL-8 monoclonal antibody cream Jin 2001
30
30
100.0 %
0.0 [ -0.06, 0.06 ]
5/46
4/46
100.0 %
0.02 [ -0.10, 0.14 ]
Subtotal (95% CI)

46
46
100.0 %
0.02 [ -0.10, 0.14 ]
3 Betamethasone-17,21-dipropionate plus salicylic acid Elie 1983 0/10 0/10 100.0 % 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

10
10
100.0 %
0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

44
41
100.0 %
0.00 [ -0.07, 0.06 ]
1/29
1/11
100.0 %
-0.06 [ -0.24, 0.13 ]
Subtotal (95% CI)

29
11
100.0 %
-0.06 [ -0.24, 0.13 ]
0/8
0/8
-1 -0.5 0 0.5 1
100.0 %
0.0 [ -0.21, 0.21 ]
Favours placebo
(Continued . . . )
384
(. . .
Continued)
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 7 Dead Sea salts emollient lotion Cheesbrough 1992
100.0 %
0.0 [ -0.21, 0.21 ]
2/12
1/12
100.0 %
0.08 [ -0.18, 0.35 ]
Subtotal (95% CI)

12
12
100.0 %
0.08 [ -0.18, 0.35 ]
1/25
0/25
100.0 %
0.04 [ -0.06, 0.14 ]
Subtotal (95% CI)

25
25
100.0 %
0.04 [ -0.06, 0.14 ]
2/15
0/15
100.0 %
0.13 [ -0.06, 0.33 ]
Subtotal (95% CI)

15
15
100.0 %
0.13 [ -0.06, 0.33 ]
0/30
0/30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
100.0 %
0.0 [ -0.06, 0.06 ]
0/7
0/7
100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

100.0 %
0.0 [ -0.24, 0.24 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable
17
17
100.0 %
0.0 [ -0.11, 0.11 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Test for overall effect: Z = 0.0 (P = 1.0) 13 Oleum horwathiensis Lassus 1991 1/25 0/25 100.0 % Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.04 [ -0.06, 0.14 ]
Subtotal (95% CI)

25
25
100.0 %
0.04 [ -0.06, 0.14 ]
Subtotal (95% CI)

73
73
100.0 %
0.01 [ -0.02, 0.05 ]
1/28
1/29
100.0 %
0.00 [ -0.09, 0.10 ]
Subtotal (95% CI)

28
29
100.0 %
0.00 [ -0.09, 0.10 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 17 Polymyxin B cream, 200,000U/g
52
52
100.0 %
0.0 [ -0.19, 0.19 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 19 Salicylic acid Elie 1983
15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/10
0/10
-1 -0.5 0 0.5 1
100.0 %
0.0 [ -0.17, 0.17 ]
Favours placebo
(Continued . . . )
(. . .
Continued)
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 20 Sirolimus (topical)
10
10
100.0 %
0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
14/112
16/55
100.0 %
-0.17 [ -0.30, -0.03 ]
Subtotal (95% CI)

112
55
100.0 %
-0.17 [ -0.30, -0.03 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
387
Analysis 6.10. Comparison 6 Other treatment vs. placebo, Outcome 10 Adverse events (systemic).
Comparison: 6 Other treatment vs. placebo Outcome: 10 Adverse events (systemic)
Study or subgroup
Other treatment n/N
Placebo n/N
Weight
1 Aloe vera extract
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 2 Anti IL-8 monoclonal antibody cream
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 5 Ciclopirox olamine shampoo
44
41
100.0 %
0.0 [ -0.04, 0.04 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 6 Ciclosporin solution in oil Cannavo 2003
0.0 %
0.0 [ 0.0, 0.0 ]
0/8
0/8
100.0 %
0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 7 Dead Sea salts emollient lotion
100.0 %
0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)
0
-1 -0.5 0 0.5 1
0.0 %
0.0 [ 0.0, 0.0 ]
Favours placebo
(Continued . . . )
388
(. . .
Study or subgroup Other treatment n/N Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 8 Fish oil plus occlusion Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 9 Hexauoro-1,25-dihydroxyvitamin D3 Durakovic 2001
0.0 %
0.0 [ 0.0, 0.0 ]
0/15
0/15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 10 Methotrexate gel Sutton 2001 Syed 2001b
15
15
100.0 %
0.0 [ -0.12, 0.12 ]
0/53 0/30
0/53 0/30
75.1 % 24.9 %
0.0 [ -0.04, 0.04 ] 0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

83
83
100.0 %
0.0 [ -0.03, 0.03 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 11 Mycophenolic acid ointment
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 12 NG-monomethyl-L-arginine (L-NMMA) cream Ormerod 2000
0.0 %
0.0 [ 0.0, 0.0 ]
0/17
0/17
100.0 %
0.0 [ -0.11, 0.11 ]
Subtotal (95% CI)

17
17
100.0 %
0.0 [ -0.11, 0.11 ]
0/25
0/25
100.0 %
0.0 [ -0.07, 0.07 ]
Subtotal (95% CI)

25
25
100.0 %
0.0 [ -0.07, 0.07 ]
-1
-0.5
0.5
Favours placebo
(Continued . . . )
(. . .
Continued)
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: not applicable 15 Pimecrolimus cream, 1% BD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 17 Polymyxin B cream, 200,000U/g
52
52
100.0 %
0.0 [ -0.04, 0.04 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

15
15
100.0 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/112
0/55
100.0 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)
112
55
-1 -0.5 0 0.5 1
100.0 %
0.0 [ -0.03, 0.03 ]
Favours placebo
(Continued . . . )
(. . .
Study or subgroup Other treatment n/N Total events: 0 (Other treatment), 0 (Placebo) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 22 Tar Placebo n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
Favours placebo
Analysis 7.1. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 1 IAGI.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 1 IAGI
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Papp 2003 (H) 308 -3 (1.21) 312 -3 (1.05) 17.1 % 0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Calcipotriol vs. betamethasone valerate Duweb 2000 Klaber 1994 Molin 1997
308
312
17.1 %
0.0 [ -0.16, 0.16 ]
24 236 205
-2.63 (0.88) -2.51 (1.14) -2.41 (0.94)
18 232 207
-2.83 (0.92) -2.93 (1.02) -2.39 (0.92)
6.2 % 16.4 % 16.1 %
0.22 [ -0.39, 0.83 ] 0.39 [ 0.20, 0.57 ] -0.02 [ -0.21, 0.17 ]
Subtotal (95% CI)
465
457
38.7 %
0.19 [ -0.13, 0.52 ]
-4
-2
(Continued . . . )
391
(. . .
Study or subgroup Vitamin D analogue N 3 Calcipotriol vs. desoxymetasone Mean(SD) Corticosteroid (potent) N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Calcipotriol vs. diorasone diacetate Medansky 1996
0.0 %
0.0 [ 0.0, 0.0 ]
128
-4.1 (1.11)
128
-4.4 (1.11)
14.5 %
0.27 [ 0.02, 0.52 ]
Subtotal (95% CI)

128
128
14.5 %
0.27 [ 0.02, 0.52 ]
Test for overall effect: Z = 2.15 (P = 0.032) 5 Calcipotriol vs. uocinonide Bruce 1994 52 -4.04 (1.31) 47 -3.3 (1.2) 10.1 % -0.58 [ -0.99, -0.18 ]
Subtotal (95% CI)

52
47
10.1 % -0.58 [ -0.99, -0.18 ]
Test for overall effect: Z = 2.84 (P = 0.0046) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 128 -3.31 (1.12) 130 -3.55 (1.21) 14.6 % 0.21 [ -0.04, 0.45 ]
Subtotal (95% CI)

128
130
14.6 %
0.21 [ -0.04, 0.45 ]
Test for overall effect: Z = 1.64 (P = 0.10) 7 Calcitriol vs. betamethasone valerate Langner 2001 (H) 15 -2.4 (1.18) 15 -2.2 (0.86) 4.9 % -0.19 [ -0.91, 0.53 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.51 (P = 0.61) 8 Tacalcitol vs. betamethasone valerate
15
15
4.9 % -0.19 [ -0.91, 0.53 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
1096
1089
100.0 %
0.07 [ -0.11, 0.26 ]
-4
-2
392
Analysis 7.2. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 2 TSS.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 2 TSS
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) 480 2.24 (0.9) 476 1.9 (0.94) 14.4 % 0.37 [ 0.24, 0.50 ]
Subtotal (95% CI)

480
476
14.4 %
0.37 [ 0.24, 0.50 ]
Test for overall effect: Z = 5.66 (P < 0.00001) 2 Calcipotriol vs. betamethasone valerate Duweb 2000 Klaber 1994 Kragballe 1991a 24 220 342 2.1 (3.57) 3.29 (5.3) 2.31 (1.97) 18 225 342 1.49 (3.57) 2.93 (4.35) 2.82 (1.97) 7.0 % 13.6 % 14.1 % 0.17 [ -0.44, 0.78 ] 0.07 [ -0.11, 0.26 ] -0.26 [ -0.41, -0.11 ]
Subtotal (95% CI)
586
585
34.8 % -0.06 [ -0.34, 0.23 ]
Heterogeneity: Tau?? = 0.04; Chi?? = 8.29, df = 2 (P = 0.02); I?? =76% Test for overall effect: Z = 0.40 (P = 0.69) 3 Calcipotriol vs. desoxymetasone
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
128
2.7 (1.51)
128
2.1 (1.51)
12.7 %
0.40 [ 0.15, 0.64 ]
Subtotal (95% CI)

128
128
12.7 %
0.40 [ 0.15, 0.64 ]
Test for overall effect: Z = 3.14 (P = 0.0017) 5 Calcipotriol vs. uocinonide Bruce 1994 44 1.92 (1.51) 45 2.66 (1.51) 9.8 % -0.49 [ -0.91, -0.06 ]
Subtotal (95% CI)

44
45
9.8 % -0.49 [ -0.91, -0.06 ]
Test for overall effect: Z = 2.26 (P = 0.024) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 128 1.58 (0.84) 130 1.36 (0.84) 12.7 % 0.26 [ 0.02, 0.51 ]
Subtotal (95% CI)

128
130
12.7 %
0.26 [ 0.02, 0.51 ]
Test for overall effect: Z = 2.09 (P = 0.037) 7 Calcitriol vs. betamethasone valerate
-4
-2
(Continued . . . )
393
(. . .
Study or subgroup Vitamin D analogue N Mean(SD) Corticosteroid (potent) N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Tacalcitol vs. betamethasone valerate Scarpa 1996 Seidenari 1997 (H)
0.0 %
0.0 [ 0.0, 0.0 ]
63 11
3.06 (1.97) 2.77 (1.48)
63 11
2.3 (1.97) 1.92 (1.4)
10.9 % 4.7 %
0.38 [ 0.03, 0.74 ] 0.57 [ -0.29, 1.42 ]
Subtotal (95% CI)
74
74
15.6 %
0.41 [ 0.08, 0.74 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 0.15, df = 1 (P = 0.70); I?? =0.0% Test for overall effect: Z = 2.47 (P = 0.014)
Total (95% CI)
1440
1438
100.0 %
0.14 [ -0.08, 0.37 ]
-4
-2
394
Analysis 7.3. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 3 PASI.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) Papp 2003 (H) 480 308 -0.46 (0.31) -0.49 (0.32) 476 312 -0.57 (0.3) -0.63 (0.27) 15.3 % 14.9 % 0.36 [ 0.23, 0.49 ] 0.47 [ 0.31, 0.63 ]
Subtotal (95% CI)
788
788
30.2 %
0.41 [ 0.30, 0.51 ]
Heterogeneity: Tau?? = 0.00; Chi?? = 1.16, df = 1 (P = 0.28); I?? =14% Test for overall effect: Z = 7.36 (P < 0.00001) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Kragballe 1991a Molin 1997 Vladimirov 1994 201 316 205 32 -5.5 (5.84) 2.5 (2.86) 3.1 (2.8) 0.97 (3.46) 200 316 207 28 -5.32 (6.02) 3.06 (3.38) 3.5 (4.3) 1.54 (3.46) 14.3 % 14.9 % 14.3 % 8.6 % -0.03 [ -0.23, 0.17 ] -0.18 [ -0.33, -0.02 ] -0.11 [ -0.30, 0.08 ] -0.16 [ -0.67, 0.35 ]
Subtotal (95% CI)
754
751
52.1 % -0.12 [ -0.22, -0.02 ]
Heterogeneity: Tau?? = 0.0; Chi?? = 1.39, df = 3 (P = 0.71); I?? =0.0% Test for overall effect: Z = 2.32 (P = 0.021) 3 Calcipotriol vs. desoxymetasone Kim 1994 10 3.69 (1.9) 10 3.4 (1.93) 4.4 % 0.15 [ -0.73, 1.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.32 (P = 0.75) 4 Calcipotriol vs. diorasone diacetate
10
10
4.4 %
0.15 [ -0.73, 1.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Calcipotriol vs. uocinonide
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003
0.0 %
0.0 [ 0.0, 0.0 ]
128
5.4 (5.06)
130
3.67 (3.79)
13.4 %
0.39 [ 0.14, 0.63 ]
Subtotal (95% CI)

128
130
13.4 %
0.39 [ 0.14, 0.63 ]
-4
-2
(Continued . . . )
395
(. . .
Study or subgroup Vitamin D analogue N 7 Calcitriol vs. betamethasone valerate Mean(SD) Corticosteroid (potent) N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Tacalcitol vs. betamethasone valerate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
1680
1679
100.0 %
0.12 [ -0.09, 0.34 ]
-4
-2
Analysis 7.4. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 4 PAGI.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 4 PAGI
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Klaber 1994 Kragballe 1991a
0.0 %
0.0 [ 0.0, 0.0 ]
198 236 342
-2.52 (0.9) -2.44 (1.07) -2.94 (0.64)
198 232 342
-2.27 (1) -2.85 (0.94) -2.77 (0.7)
32.9 % 33.2 % 33.9 %
-0.26 [ -0.46, -0.06 ] 0.41 [ 0.22, 0.59 ] -0.25 [ -0.40, -0.10 ]
Subtotal (95% CI)
776
772
100.0 % -0.04 [ -0.46, 0.39 ]
Heterogeneity: Tau?? = 0.13; Chi?? = 35.26, df = 2 (P<0.00001); I?? =94%
-4
-2
(Continued . . . )
396
(. . .
Study or subgroup Vitamin D analogue N Test for overall effect: Z = 0.17 (P = 0.86) 3 Calcipotriol vs. desoxymetasone Mean(SD) Corticosteroid (potent) N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 Calcipotriol vs. diorasone diacetate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Calcitriol vs. betamethasone dipropionate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 7 Calcitriol vs. betamethasone valerate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Tacalcitol vs. betamethasone valerate
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
776
772
100.0 % -0.04 [ -0.46, 0.39 ]
-4
-2
397
Analysis 7.5. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) Papp 2003 (H) 480 308 2.24 (0.9) -3 (1.21) 476 312 1.9 (0.94) -3 (1.05) 9.5 % 9.2 % 0.37 [ 0.24, 0.50 ] 0.0 [ -0.16, 0.16 ]
Subtotal (95% CI)
788
788
18.7 %
0.19 [ -0.17, 0.55 ]
Heterogeneity: Tau?? = 0.06; Chi?? = 12.73, df = 1 (P = 0.00036); I?? =92% Test for overall effect: Z = 1.02 (P = 0.31) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Duweb 2000 Klaber 1994 Kragballe 1991a Molin 1997 Vladimirov 1994 201 24 236 342 205 32 -5.5 (5.84) -2.63 (0.88) -2.51 (1.14) 2.31 (1.97) -2.41 (0.94) 0.97 (3.46) 200 18 232 342 207 28 -5.32 (6.02) -2.83 (0.92) -2.93 (1.02) 2.82 (1.97) -2.39 (0.92) 1.54 (3.46) 8.8 % 3.9 % 8.9 % 9.3 % 8.8 % 4.8 % -0.03 [ -0.23, 0.17 ] 0.22 [ -0.39, 0.83 ] 0.39 [ 0.20, 0.57 ] -0.26 [ -0.41, -0.11 ] -0.02 [ -0.21, 0.17 ] -0.16 [ -0.67, 0.35 ]
Subtotal (95% CI)
1040
1027
44.5 %
0.02 [ -0.22, 0.25 ]
Heterogeneity: Tau?? = 0.06; Chi?? = 29.56, df = 5 (P = 0.00002); I?? =83% Test for overall effect: Z = 0.13 (P = 0.90) 3 Calcipotriol vs. desoxymetasone Kim 1994 10 3.69 (1.9) 10 3.4 (1.93) 2.4 % 0.15 [ -0.73, 1.02 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.32 (P = 0.75) 4 Calcipotriol vs. diorasone diacetate Medansky 1996
10
10
2.4 %
0.15 [ -0.73, 1.02 ]
128
-4.1 (1.11)
128
-4.4 (1.11)
8.1 %
0.27 [ 0.02, 0.52 ]
Subtotal (95% CI)

128
128
8.1 %
0.27 [ 0.02, 0.52 ]
Test for overall effect: Z = 2.15 (P = 0.032) 5 Calcipotriol vs. uocinonide Bruce 1994 52 -4.04 (1.31) 47 -3.3 (1.2) 6.0 % -0.58 [ -0.99, -0.18 ]
Subtotal (95% CI)
52
47
-4 -2 0 2 4
6.0 % -0.58 [ -0.99, -0.18 ]
(Continued . . . )
398
(. . .
Study or subgroup Vitamin D analogue N Heterogeneity: not applicable Test for overall effect: Z = 2.84 (P = 0.0046) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 128 -3.31 (1.12) 130 -3.55 (1.21) 8.1 % Mean(SD) Corticosteroid (potent) N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
0.21 [ -0.04, 0.45 ]
Subtotal (95% CI)

128
130
8.1 %
0.21 [ -0.04, 0.45 ]
Test for overall effect: Z = 1.64 (P = 0.10) 7 Calcitriol vs. betamethasone valerate Langner 2001 (H) 15 -2.4 (1.18) 15 -2.2 (0.86) 3.2 % -0.19 [ -0.91, 0.53 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.51 (P = 0.61) 8 Tacalcitol vs. betamethasone valerate Scarpa 1996 Seidenari 1997 (H)
15
15
3.2 % -0.19 [ -0.91, 0.53 ]
63 11
3.06 (1.97) 2.77 (1.48)
63 11
2.3 (1.97) 1.92 (1.4)
6.6 % 2.4 %
0.38 [ 0.03, 0.74 ] 0.57 [ -0.29, 1.42 ]
Subtotal (95% CI)
74
74
9.1 %
0.41 [ 0.08, 0.74 ]
Total (95% CI)
2235
2219
100.0 %
0.08 [ -0.07, 0.24 ]
-4
-2
399
Analysis 7.6. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 6 Total withdrawals.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 6 Total withdrawals
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) Papp 2003 (H) 39/480 27/308 22/476 17/313 20.4 % 11.9 % 0.04 [ 0.00, 0.07 ] 0.03 [ -0.01, 0.07 ]
Subtotal (95% CI)
788
789
32.4 %
0.03 [ 0.01, 0.06 ]
Total events: 66 (Vitamin D analogue), 39 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.0; Chi?? = 0.00, df = 1 (P = 0.95); I?? =0.0% Test for overall effect: Z = 2.75 (P = 0.0059) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Duweb 2000 Klaber 1994 Kragballe 1991a Molin 1997 21/205 0/24 20/240 15/345 14/210 17/204 0/18 9/234 15/345 7/211 6.2 % 2.4 % 10.6 % 21.0 % 11.3 % 0.02 [ -0.04, 0.08 ] 0.0 [ -0.09, 0.09 ] 0.04 [ 0.00, 0.09 ] 0.0 [ -0.03, 0.03 ] 0.03 [ -0.01, 0.07 ]
Subtotal (95% CI)
1024
1012
51.5 %
0.02 [ 0.00, 0.04 ]
Total events: 70 (Vitamin D analogue), 48 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.0; Chi?? = 3.59, df = 4 (P = 0.46); I?? =0.0% Test for overall effect: Z = 1.91 (P = 0.057) 3 Calcipotriol vs. desoxymetasone
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total events: 0 (Vitamin D analogue), 0 (Corticosteroid (potent))
6/134
6/134
7.9 %
0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 5 Calcipotriol vs. uocinonide
134
134
7.9 %
0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)
0.0 %
0.0 [ 0.0, 0.0 ]
-0.5
-0.25
0.25
0.5
(Continued . . . )
400
(. . .
Study or subgroup Vitamin D analogue n/N Heterogeneity: not applicable Test for overall effect: not applicable 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 6/128 9/130 6.0 % Corticosteroid (potent) n/N Risk Difference MH,Random,95% CI Weight
Continued)
-0.02 [ -0.08, 0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.77 (P = 0.44) 7 Calcitriol vs. betamethasone valerate Langner 2001 (H)
128
130
6.0 %
-0.02 [ -0.08, 0.03 ]
1/15
0/15
0.7 %
0.07 [ -0.10, 0.23 ]
Subtotal (95% CI)

15
15
0.7 %
0.07 [ -0.10, 0.23 ]
13/76 3/14
13/76 3/14
1.4 % 0.2 %
0.0 [ -0.12, 0.12 ] 0.0 [ -0.30, 0.30 ]
Subtotal (95% CI)
90
90
1.6 %
0.0 [ -0.11, 0.11 ]
Total events: 16 (Vitamin D analogue), 16 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
Total (95% CI)
2179
2170
100.0 %
0.02 [ 0.01, 0.03 ]
-0.5
-0.25
0.25
0.5
401
Analysis 7.7. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 7 Withdrawals due to adverse events.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) 15/480 5/476 16.4 % 0.02 [ 0.00, 0.04 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 2.25 (P = 0.024) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Duweb 2000 Klaber 1994 Kragballe 1991a Molin 1997
480
476
16.4 %
0.02 [ 0.00, 0.04 ]
4/205 0/24 11/240 2/345 6/210
2/204 0/18 2/234 1/345 3/211
11.2 % 0.9 % 7.7 % 32.7 % 8.4 %
0.01 [ -0.01, 0.03 ] 0.0 [ -0.09, 0.09 ] 0.04 [ 0.01, 0.07 ] 0.00 [ -0.01, 0.01 ] 0.01 [ -0.01, 0.04 ]
Subtotal (95% CI)
1024
1012
60.9 %
0.01 [ 0.00, 0.03 ]
Total events: 23 (Vitamin D analogue), 8 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.00; Chi?? = 8.07, df = 4 (P = 0.09); I?? =50% Test for overall effect: Z = 1.56 (P = 0.12) 3 Calcipotriol vs. desoxymetasone
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Calcipotriol vs. uocinonide Bruce 1994
0.0 %
0.0 [ 0.0, 0.0 ]
0/57
1/57
3.2 %
-0.02 [ -0.06, 0.03 ]
Subtotal (95% CI)

57
57
3.2 %
-0.02 [ -0.06, 0.03 ]
-0.5
-0.25
0.25
0.5
(Continued . . . )
402
(. . .
Study or subgroup Vitamin D analogue n/N Test for overall effect: Z = 0.73 (P = 0.47) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 2/128 1/130 9.2 % Corticosteroid (potent) n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.01 [ -0.02, 0.03 ]
Subtotal (95% CI)

128
130
9.2 %
0.01 [ -0.02, 0.03 ]
1/15
0/15
0.3 %
0.07 [ -0.10, 0.23 ]
Subtotal (95% CI)

15
15
0.3 %
0.07 [ -0.10, 0.23 ]
0/76 0/14
0/76 0/14
9.7 % 0.5 %
0.0 [ -0.03, 0.03 ] 0.0 [ -0.13, 0.13 ]
Subtotal (95% CI)
90
90
10.1 %
0.0 [ -0.02, 0.02 ]
Total (95% CI)
1794
1780
100.0 %
0.01 [ 0.00, 0.02 ]
Total events: 41 (Vitamin D analogue), 15 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.00; Chi?? = 12.08, df = 10 (P = 0.28); I?? =17% Test for overall effect: Z = 2.23 (P = 0.026)
-0.5
-0.25
0.25
0.5
403
Analysis 7.8. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 8 Withdrawals due to treatment failure.
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Duweb 2000 Klaber 1994 Kragballe 1991a
0.0 %
0.0 [ 0.0, 0.0 ]
6/205 0/24 4/240 1/345
6/204 0/18 2/234 2/345
6.0 % 0.8 % 16.1 % 67.0 %
0.00 [ -0.03, 0.03 ] 0.0 [ -0.09, 0.09 ] 0.01 [ -0.01, 0.03 ] 0.00 [ -0.01, 0.01 ]
Subtotal (95% CI)
814
801
89.9 %
0.00 [ -0.01, 0.01 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/57
0/56
5.6 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003
57
56
5.6 %
0.0 [ -0.03, 0.03 ]
4/128
3/130
-1 -0.5 0 0.5 1
4.1 %
0.01 [ -0.03, 0.05 ]
(Continued . . . )
404
(. . .
Study or subgroup Vitamin D analogue n/N Corticosteroid (potent) n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

128
130
4.1 %
0.01 [ -0.03, 0.05 ]
0/15
0/15
0.4 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 8 Tacalcitol vs. betamethasone valerate
15
15
0.4 %
0.0 [ -0.12, 0.12 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
1014
1002
100.0 %
0.00 [ -0.01, 0.01 ]
-1
-0.5
0.5
405
Analysis 7.9. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 9 Adverse events (local).
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 9 Adverse events (local)
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Kaufmann 2002 (H) Papp 2003 (H) 54/480 53/308 23/476 27/313 11.6 % 11.0 % 0.06 [ 0.03, 0.10 ] 0.09 [ 0.03, 0.14 ]
Subtotal (95% CI)
788
789
22.6 %
0.07 [ 0.04, 0.10 ]
Total events: 107 (Vitamin D analogue), 50 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.0; Chi?? = 0.48, df = 1 (P = 0.49); I?? =0.0% Test for overall effect: Z = 4.83 (P < 0.00001) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Duweb 2000 Klaber 1994 Kragballe 1991a Molin 1997 64/205 2/24 84/240 37/345 49/207 18/204 0/18 26/234 35/345 21/210 9.9 % 6.8 % 10.0 % 11.2 % 10.1 % 0.22 [ 0.15, 0.30 ] 0.08 [ -0.05, 0.22 ] 0.24 [ 0.17, 0.31 ] 0.01 [ -0.04, 0.05 ] 0.14 [ 0.07, 0.21 ]
Subtotal (95% CI)
1021
1011
48.1 %
0.14 [ 0.03, 0.25 ]
Total events: 236 (Vitamin D analogue), 100 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.01; Chi?? = 44.21, df = 4 (P<0.00001); I?? =91% Test for overall effect: Z = 2.53 (P = 0.012) 3 Calcipotriol vs. desoxymetasone
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
10/57
4/56
7.7 %
0.10 [ -0.02, 0.22 ]
Subtotal (95% CI)
57
56
-1 -0.5 0 0.5 1
7.7 %
0.10 [ -0.02, 0.22 ]
(Continued . . . )
406
(. . .
Study or subgroup Vitamin D analogue n/N Total events: 10 (Vitamin D analogue), 4 (Corticosteroid (potent)) Heterogeneity: not applicable Test for overall effect: Z = 1.70 (P = 0.088) 6 Calcitriol vs. betamethasone dipropionate Camarasa 2003 7/128 7/130 10.8 % Corticosteroid (potent) n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.00 [ -0.05, 0.06 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.03 (P = 0.98) 7 Calcitriol vs. betamethasone valerate
128
130
10.8 %
0.00 [ -0.05, 0.06 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Tacalcitol vs. betamethasone valerate Scarpa 1996
0.0 %
0.0 [ 0.0, 0.0 ]
2/76
3/76
10.8 %
-0.01 [ -0.07, 0.04 ]
Subtotal (95% CI)

76
76
10.8 %
-0.01 [ -0.07, 0.04 ]
Total (95% CI)
2070
2062
100.0 %
0.09 [ 0.04, 0.14 ]
Total events: 362 (Vitamin D analogue), 164 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.01; Chi?? = 71.30, df = 9 (P<0.00001); I?? =87% Test for overall effect: Z = 3.24 (P = 0.0012)
-1
-0.5
0.5
407
Analysis 7.10. Comparison 7 Vitamin D analogues vs. corticosteroid (potent), Outcome 10 Adverse events (systemic).
Comparison: 7 Vitamin D analogues vs. corticosteroid (potent) Outcome: 10 Adverse events (systemic)
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate Papp 2003 (H) 0/308 0/313 28.4 % 0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 2 Calcipotriol vs. betamethasone valerate Cunliffe 1992 Klaber 1994 Kragballe 1991a Molin 1997
308
313
28.4 %
0.0 [ -0.01, 0.01 ]
1/205 0/240 0/345 0/207
1/204 0/234 0/345 0/210
6.1 % 16.6 % 35.0 % 12.8 %
0.00 [ -0.01, 0.01 ] 0.0 [ -0.01, 0.01 ] 0.0 [ -0.01, 0.01 ] 0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)
997
993
70.5 %
0.00 [ 0.00, 0.00 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 6 Calcitriol vs. betamethasone dipropionate
0.0 %
0.0 [ 0.0, 0.0 ]
-0.5
-0.25
0.25
0.5
(Continued . . . )
408
(. . .
Study or subgroup Vitamin D analogue n/N Camarasa 2003 2/128 Corticosteroid (potent) n/N 3/130 Risk Difference MH,Random,95% CI Weight
Continued)
Risk Difference MH,Random,95% CI -0.01 [ -0.04, 0.03 ]
1.0 %
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.43 (P = 0.66) 7 Calcitriol vs. betamethasone valerate
128
130
1.0 %
-0.01 [ -0.04, 0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 Tacalcitol vs. betamethasone valerate Scarpa 1996
0.0 %
0.0 [ 0.0, 0.0 ]
7/76
7/76
0.1 %
0.0 [ -0.09, 0.09 ]
Subtotal (95% CI)

76
76
0.1 %
0.0 [ -0.09, 0.09 ]
Total (95% CI)
1509
1512
100.0 %
0.00 [ 0.00, 0.00 ]
-0.5
-0.25
0.25
0.5
409
Analysis 8.2. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 2 TSS.
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 2 TSS
Study or subgroup
Corticosteroid (v potent) N Mean(SD)
Weight
1 Calcipotriol vs. Clobetasol propionate Reygagne 2002b 75 2.36 (1.64) 76 1.76 (1.57) 100.0 % 0.37 [ 0.05, 0.69 ]
Total (95% CI)

75
76
100.0 % 0.37 [ 0.05, 0.69 ]
-10
-5
10
Analysis 8.3. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 3 PASI.
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. Clobetasol propionate Landi 1993 20 1.33 (1.4) 20 2.02 (2.6) 100.0 % -0.32 [ -0.95, 0.30 ]
Total (95% CI)

20
20
100.0 % -0.32 [ -0.95, 0.30 ]
-10
-5
10
410
Analysis 8.5. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. Clobetasol propionate Landi 1993 Reygagne 2002b 20 75 1.33 (1.4) 2.36 (1.64) 20 76 2.02 (2.6) 1.76 (1.57) 42.3 % 57.7 % -0.32 [ -0.95, 0.30 ] 0.37 [ 0.05, 0.69 ]
Total (95% CI)
95
96
100.0 % 0.08 [ -0.60, 0.75 ]
-10
-5
10
Analysis 8.6. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 6 Total withdrawals.
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 6 Total withdrawals
Study or subgroup
Corticosteroid (v potent) n/N
Weight
1 Calcipotriol vs. Clobetasol propionate K??se 1997 0/21 0/22 100.0 % 0.0 [ -0.09, 0.09 ]
Total (95% CI)

21
22
100.0 %
0.0 [ -0.09, 0.09 ]
Total events: 0 (Vitamin D analogue), 0 (Corticosteroid (v potent))
-1
-0.5
0.5
411
Analysis 8.7. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 7 Withdrawals due to adverse events.
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Weight
Total (95% CI)

21
22
100.0 %
0.0 [ -0.09, 0.09 ]
-1
-0.5
0.5
Analysis 8.8. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 8 Withdrawals due to treatment failure.
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Weight
Total (95% CI)

21
22
100.0 %
0.0 [ -0.09, 0.09 ]
-1
-0.5
0.5
412
Analysis 8.9. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 9 Adverse events (local).
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 9 Adverse events (local)
Study or subgroup
Weight
1 Calcipotriol vs. Clobetasol propionate K??se 1997 Landi 1993 Reygagne 2002b 4/21 0/20 17/75 2/22 1/20 1/76 27.7 % 34.9 % 37.4 % 0.10 [ -0.11, 0.31 ] -0.05 [ -0.18, 0.08 ] 0.21 [ 0.12, 0.31 ]
Total (95% CI)
116
118
100.0 %
0.09 [ -0.10, 0.28 ]
Total events: 21 (Vitamin D analogue), 4 (Corticosteroid (v potent)) Heterogeneity: Tau?? = 0.02; Chi?? = 11.09, df = 2 (P = 0.004); I?? =82% Test for overall effect: Z = 0.94 (P = 0.35)
-1
-0.5
0.5
Analysis 8.10. Comparison 8 Vitamin D analogues vs. corticosteroid (very potent), Outcome 10 Adverse events (systemic).
Comparison: 8 Vitamin D analogues vs. corticosteroid (very potent) Outcome: 10 Adverse events (systemic)
Study or subgroup
Weight
1 Calcipotriol vs. Clobetasol propionate Landi 1993 0/20 1/20 100.0 % -0.05 [ -0.18, 0.08 ]
Total (95% CI)

20
20
100.0 %
-0.05 [ -0.18, 0.08 ]
-1
-0.5
0.5
413
Analysis 9.1. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 1 IAGI.
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 1 IAGI
Study or subgroup
Vitamin D analogue-potent steroid combination N Mean(SD)
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 369 -3.72 (0.96) 363 -3.25 (1.1) 100.0 % -0.46 [ -0.60, -0.31 ]
Total (95% CI)

369
363
100.0 % -0.46 [ -0.60, -0.31 ]
-10
-5
10
Favours vitamin D combination
Analysis 9.2. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 2 TSS.
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 2 TSS
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Kaufmann 2002 (H) 490 1.5 (0.9) 476 1.9 (0.94) 100.0 % -0.43 [ -0.56, -0.31 ]
Total (95% CI)

490
476
100.0 % -0.43 [ -0.56, -0.31 ]
-10
-5
10
414
Analysis 9.3. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 3 PASI.
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 3 PASI
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 Kaufmann 2002 (H) 342 490 2.5 (2.5) -71.3 (25.7) 343 476 3.9 (3.7) -57.2 (29.8) 41.7 % 58.3 % -0.44 [ -0.59, -0.29 ] -0.51 [ -0.64, -0.38 ]
Total (95% CI)
832
819
100.0 % -0.48 [ -0.58, -0.38 ]
-10
-5
10
415
Analysis 9.5. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 Kaufmann 2002 (H) 369 490 -3.72 (0.96) 1.5 (0.9) 363 476 -3.25 (1.1) 1.9 (0.94) 43.1 % 56.9 % -0.46 [ -0.60, -0.31 ] -0.43 [ -0.56, -0.31 ]
Total (95% CI)
859
839
100.0 % -0.44 [ -0.54, -0.35 ]
-4
-2
Analysis 9.6. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 6 Total withdrawals.
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 6 Total withdrawals
Study or subgroup
Vitamin D analogue-potent steroid combination n/N
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 Kaufmann 2002 (H) 28/372 13/490 21/365 22/476 43.7 % 56.3 % 0.02 [ -0.02, 0.05 ] -0.02 [ -0.04, 0.00 ]
Total (95% CI)
862
841
100.0 %
0.00 [ -0.04, 0.03 ]
Total events: 41 (Vitamin D analogue-potent steroid combination), 43 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.00; Chi?? = 3.15, df = 1 (P = 0.08); I?? =68% Test for overall effect: Z = 0.17 (P = 0.86)
-0.2
-0.1
0.1
0.2
416
Analysis 9.7. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 7 Withdrawals due to adverse events.
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Kaufmann 2002 (H) 3/490 5/476 100.0 % 0.00 [ -0.02, 0.01 ]
Total (95% CI)

490
476
100.0 %
0.00 [ -0.02, 0.01 ]
Total events: 3 (Vitamin D analogue-potent steroid combination), 5 (Corticosteroid (potent))
-0.2
-0.1
0.1
0.2
417
Analysis 9.9. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 9 Adverse events (local).
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 9 Adverse events (local)
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 Kaufmann 2002 (H) 30/372 29/490 17/365 23/476 39.8 % 60.2 % 0.03 [ 0.00, 0.07 ] 0.01 [ -0.02, 0.04 ]
Total (95% CI)
862
841
100.0 %
0.02 [ 0.00, 0.04 ]
Total events: 59 (Vitamin D analogue-potent steroid combination), 40 (Corticosteroid (potent)) Heterogeneity: Tau?? = 0.00; Chi?? = 1.02, df = 1 (P = 0.31); I?? =2% Test for overall effect: Z = 1.76 (P = 0.078)
-0.2
-0.1
0.1
0.2
Analysis 9.10. Comparison 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid, Outcome 10 Adverse events (systemic).
Comparison: 9 Vitamin D analogues-potent steroid combination vs. potent corticosteroid Outcome: 10 Adverse events (systemic)
Study or subgroup
Weight
1 Dovobet vs. betamethasone dipropionate Douglas 2002 0/372 0/365 100.0 % 0.0 [ -0.01, 0.01 ]
Total (95% CI)

372
365
100.0 %
0.0 [ -0.01, 0.01 ]
Total events: 0 (Vitamin D analogue-potent steroid combination), 0 (Corticosteroid (potent))
-0.2
-0.1
0.1
0.2
418
Analysis 10.1. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 1 IAGI.

Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 1 IAGI
Study or subgroup
Dithranol N Mean(SD)
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Christensen 1999 Wall 1998 231 89 153 -2.81 (0.6) -3.4 (1.52) -2.48 (0.88) 227 77 131 -2.29 (0.97) -2.6 (1.52) -1.69 (0.96) 26.3 % 24.6 % 25.6 % -0.64 [ -0.83, -0.46 ] -0.52 [ -0.83, -0.21 ] -0.86 [ -1.10, -0.61 ]
Subtotal (95% CI)
473
435
76.5 % -0.69 [ -0.86, -0.51 ]
Heterogeneity: Tau?? = 0.01; Chi?? = 3.15, df = 2 (P = 0.21); I?? =37% Test for overall effect: Z = 7.71 (P < 0.00001) 2 Tacalcitol vs. dithranol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcitriol vs. dithranol Hutchinson 2000
0.0 %
0.0 [ 0.0, 0.0 ]
60
-2.19 (0.52)
54
-2.44 (0.45)
23.5 %
0.51 [ 0.13, 0.88 ]
Subtotal (95% CI)

60
54
23.5 %
0.51 [ 0.13, 0.88 ]
Total (95% CI)
533
489
100.0 %
-0.40 [ -0.87, 0.07 ]
-4
-2
Favours dithranol
419
Analysis 10.2. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 2 TSS.

Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 2 TSS
Study or subgroup
Weight
1 Calcipotriol vs. dithranol Christensen 1999 Grattan 1997 (H) 89 22 2.38 (1.67) 1.8 (2) 77 22 3.72 (1.67) 2.2 (2.6) 27.7 % 20.9 % -0.80 [ -1.12, -0.48 ] -0.17 [ -0.76, 0.42 ]
Subtotal (95% CI)
111
99
48.6 % -0.54 [ -1.14, 0.07 ]
Heterogeneity: Tau?? = 0.14; Chi?? = 3.37, df = 1 (P = 0.07); I?? =70% Test for overall effect: Z = 1.73 (P = 0.084) 2 Tacalcitol vs. dithranol Farkas 1999 42 -6.1 (2.4) 42 -5.7 (2.1) 25.0 % -0.18 [ -0.60, 0.25 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.80 (P = 0.42) 3 Calcitriol vs. dithranol Hutchinson 2000
42
42
25.0 % -0.18 [ -0.60, 0.25 ]
60
1.65 (0.76)
54
1.54 (0.95)
26.5 %
0.13 [ -0.24, 0.50 ]
Subtotal (95% CI)

60
54
26.5 %
0.13 [ -0.24, 0.50 ]
Total (95% CI)
213
195
100.0 % -0.27 [ -0.73, 0.19 ]
-4
-2
Favours dithranol
420
Analysis 10.3. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 3 PASI.

Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Monastirli 2000 214 35 3.4 (2.7) 2.58 (1.18) 208 35 4.7 (4.4) 0.34 (0.51) 26.2 % 23.4 % -0.36 [ -0.55, -0.16 ] 2.44 [ 1.81, 3.06 ]
Subtotal (95% CI)
249
243
49.6 %
1.02 [ -1.71, 3.76 ]
Heterogeneity: Tau?? = 3.85; Chi?? = 69.85, df = 1 (P<0.00001); I?? =99% Test for overall effect: Z = 0.73 (P = 0.46) 2 Tacalcitol vs. dithranol Farkas 1999 42 4.16 (3.22) 42 4.38 (3.05) 25.0 % -0.07 [ -0.50, 0.36 ]
Subtotal (95% CI)

42
42
25.0 % -0.07 [ -0.50, 0.36 ]
60
3.8 (3.9)
54
4.7 (5.5)
25.4 %
-0.19 [ -0.56, 0.18 ]
Subtotal (95% CI)

60
54
25.4 % -0.19 [ -0.56, 0.18 ]
Total (95% CI)
351
339
100.0 %
0.41 [ -0.47, 1.29 ]
-10
-5
10
Favours dithranol
421
Analysis 10.4. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 4 PAGI.

Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 4 PAGI
Study or subgroup
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b 231 -2.72 (0.74) 227 -2.31 (1) 100.0 % -0.47 [ -0.65, -0.28 ]
Subtotal (95% CI)

231
227
100.0 % -0.47 [ -0.65, -0.28 ]
Test for overall effect: Z = 4.92 (P < 0.00001) 2 Tacalcitol vs. dithranol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcitriol vs. dithranol
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)

231
227
100.0 % -0.47 [ -0.65, -0.28 ]
-4
-2
Favours dithranol
422
Analysis 10.5. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Christensen 1999 Grattan 1997 (H) Monastirli 2000 Wall 1998 231 89 22 35 153 -2.81 (0.6) -3.4 (1.52) 1.8 (2) 2.58 (1.18) -2.48 (0.88) 227 77 22 35 131 -2.29 (0.97) -2.6 (1.52) 2.2 (2.6) 0.34 (0.51) -1.69 (0.96) 15.2 % 14.8 % 13.2 % 13.0 % 15.0 % -0.64 [ -0.83, -0.46 ] -0.52 [ -0.83, -0.21 ] -0.17 [ -0.76, 0.42 ] 2.44 [ 1.81, 3.06 ] -0.86 [ -1.10, -0.61 ]
Subtotal (95% CI)
530
492
71.3 % -0.01 [ -0.71, 0.69 ]
Heterogeneity: Tau?? = 0.58; Chi?? = 96.06, df = 4 (P<0.00001); I?? =96% Test for overall effect: Z = 0.03 (P = 0.98) 2 Tacalcitol vs. dithranol Farkas 1999 42 -6.1 (2.4) 42 -5.7 (2.1) 14.2 % -0.18 [ -0.60, 0.25 ]
Subtotal (95% CI)

42
42
14.2 % -0.18 [ -0.60, 0.25 ]
60
-2.19 (0.52)
54
-2.44 (0.45)
14.5 %
0.51 [ 0.13, 0.88 ]
Subtotal (95% CI)

60
54
14.5 %
0.51 [ 0.13, 0.88 ]
Total (95% CI)
632
588
100.0 %
0.04 [ -0.53, 0.61 ]
-4
-2
Favours dithranol
423
Analysis 10.6. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 6 Total withdrawals.
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 6 Total withdrawals
Study or subgroup
Dithranol n/N
Weight
1 Calcipotriol vs. dithranol Christensen 1999 Grattan 1997 (H) Monastirli 2000 van der Vleuten 1995 0/89 3/25 0/35 0/10 5/82 3/25 0/35 0/10 39.1 % 3.7 % 41.4 % 4.0 % -0.06 [ -0.12, -0.01 ] 0.0 [ -0.18, 0.18 ] 0.0 [ -0.05, 0.05 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
159
152
88.2 %
-0.03 [ -0.06, 0.01 ]
Total events: 3 (Vitamin D analogue), 8 (Dithranol) Heterogeneity: Tau?? = 0.0; Chi?? = 2.69, df = 3 (P = 0.44); I?? =0.0% Test for overall effect: Z = 1.43 (P = 0.15) 2 Tacalcitol vs. dithranol Farkas 1999 4/42 5/42 6.9 % -0.02 [ -0.16, 0.11 ]
Subtotal (95% CI)

42
42
6.9 %
-0.02 [ -0.16, 0.11 ]
Total events: 4 (Vitamin D analogue), 5 (Dithranol)
12/60
16/54
4.8 %
-0.10 [ -0.25, 0.06 ]
Subtotal (95% CI)

60
54
4.8 %
-0.10 [ -0.25, 0.06 ]
Total (95% CI)
261
248
100.0 %
-0.03 [ -0.06, 0.00 ]
Total events: 19 (Vitamin D analogue), 29 (Dithranol) Heterogeneity: Tau?? = 0.0; Chi?? = 4.07, df = 5 (P = 0.54); I?? =0.0% Test for overall effect: Z = 1.70 (P = 0.090)
-1
-0.5
0.5
Favours dithranol
424
Analysis 10.7. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 7 Withdrawals due to adverse events.
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Dithranol n/N
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Lister 1997 Monastirli 2000 van der Vleuten 1995 Wall 1998 4/239 2/89 0/35 0/10 9/161 12/239 6/82 0/35 0/10 20/145 45.7 % 13.0 % 18.0 % 1.8 % 12.2 % -0.03 [ -0.07, 0.00 ] -0.05 [ -0.11, 0.01 ] 0.0 [ -0.05, 0.05 ] 0.0 [ -0.17, 0.17 ] -0.08 [ -0.15, -0.02 ]
Subtotal (95% CI)
534
511
90.8 %
-0.04 [ -0.06, -0.01 ]
Total events: 15 (Vitamin D analogue), 38 (Dithranol) Heterogeneity: Tau?? = 0.00; Chi?? = 5.05, df = 4 (P = 0.28); I?? =21% Test for overall effect: Z = 2.43 (P = 0.015) 2 Tacalcitol vs. dithranol
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Dithranol) Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcitriol vs. dithranol Hutchinson 2000
0.0 %
0.0 [ 0.0, 0.0 ]
1/60
4/54
9.2 %
-0.06 [ -0.13, 0.02 ]
Subtotal (95% CI)

60
54
9.2 %
-0.06 [ -0.13, 0.02 ]
Total (95% CI)
594
565
100.0 %
-0.04 [ -0.06, -0.01 ]
Total events: 16 (Vitamin D analogue), 42 (Dithranol) Heterogeneity: Tau?? = 0.00; Chi?? = 5.28, df = 5 (P = 0.38); I?? =5% Test for overall effect: Z = 3.07 (P = 0.0021)
-1
-0.5
0.5
Favours dthranol
425
Analysis 10.8. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 8 Withdrawals due to treatment failure.
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Dithranol n/N
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Monastirli 2000 van der Vleuten 1995 3/239 0/35 0/10 3/239 0/35 0/10 79.3 % 10.8 % 1.0 % 0.0 [ -0.02, 0.02 ] 0.0 [ -0.05, 0.05 ] 0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)
284
284
91.2 %
0.0 [ -0.02, 0.02 ]
Total events: 3 (Vitamin D analogue), 3 (Dithranol) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 2 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 2 Tacalcitol vs. dithranol
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Dithranol) Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcitriol vs. dithranol Hutchinson 2000
0.0 %
0.0 [ 0.0, 0.0 ]
1/60
2/54
8.8 %
-0.02 [ -0.08, 0.04 ]
Subtotal (95% CI)

60
54
8.8 %
-0.02 [ -0.08, 0.04 ]
Total (95% CI)
344
338
100.0 %
0.00 [ -0.02, 0.02 ]
-1
-0.5
0.5
Favours dithranol
426
Analysis 10.9. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 9 Adverse events (local).
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 9 Adverse events (local)
Study or subgroup
Dithranol n/N
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b Christensen 1999 Grattan 1997 (H) Lister 1997 Monastirli 2000 Wall 1998 84/239 11/89 1/22 23/82 5/35 28/161 127/239 23/82 11/22 11/89 16/35 71/145 13.3 % 12.9 % 11.1 % 12.9 % 11.6 % 13.2 % -0.18 [ -0.27, -0.09 ] -0.16 [ -0.28, -0.04 ] -0.45 [ -0.68, -0.23 ] 0.16 [ 0.04, 0.28 ] -0.31 [ -0.52, -0.11 ] -0.32 [ -0.42, -0.22 ]
Subtotal (95% CI)
628
612
75.0 %
-0.20 [ -0.36, -0.04 ]
Total events: 152 (Vitamin D analogue), 259 (Dithranol) Heterogeneity: Tau?? = 0.03; Chi?? = 45.43, df = 5 (P<0.00001); I?? =89% Test for overall effect: Z = 2.50 (P = 0.012) 2 Tacalcitol vs. dithranol Farkas 1999 2/42 17/42 12.3 % -0.36 [ -0.52, -0.20 ]
Subtotal (95% CI)

42
42
12.3 %
-0.36 [ -0.52, -0.20 ]
3/60
39/54
12.7 %
-0.67 [ -0.80, -0.54 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 10.01 (P < 0.00001)
60
54
12.7 %
-0.67 [ -0.80, -0.54 ]
Total (95% CI)
730
708
100.0 %
-0.28 [ -0.45, -0.11 ]
Total events: 157 (Vitamin D analogue), 315 (Dithranol) Heterogeneity: Tau?? = 0.05; Chi?? = 96.42, df = 7 (P<0.00001); I?? =93% Test for overall effect: Z = 3.25 (P = 0.0011)
-1
-0.5
0.5
Favours dithranol
427
Analysis 10.10. Comparison 10 Vitamin D analogues vs. dithranol, Outcome 10 Adverse events (systemic).
Comparison: 10 Vitamin D analogues vs. dithranol Outcome: 10 Adverse events (systemic)
Study or subgroup
Dithranol n/N
Weight
1 Calcipotriol vs. dithranol Berth Jones 1992b van der Vleuten 1995 0/239 0/35 1/239 0/35 81.5 % 3.7 % 0.00 [ -0.02, 0.01 ] 0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)
274
274
85.2 %
0.00 [ -0.02, 0.01 ]
Total events: 0 (Vitamin D analogue), 1 (Dithranol) Heterogeneity: Tau?? = 0.0; Chi?? = 0.03, df = 1 (P = 0.87); I?? =0.0% Test for overall effect: Z = 0.70 (P = 0.49) 2 Tacalcitol vs. dithranol Farkas 1999 0/42 0/42 5.3 % 0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)

42
42
5.3 %
0.0 [ -0.05, 0.05 ]
0/60
0/54
9.5 %
0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)

60
54
9.5 %
0.0 [ -0.03, 0.03 ]
Total (95% CI)
376
370
100.0 %
0.00 [ -0.01, 0.01 ]
-1
-0.5
0.5
Favours dithranol
428
Analysis 11.1. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 1 IAGI.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 1 IAGI
Study or subgroup
Coal tar N Mean(SD)
Weight
1 calcipotriol vs. coal tar De Simone 1993 15 -2.7 (0.88) 15 -1.8 (0.86) 36.7 % -1.01 [ -1.77, -0.24 ]
Subtotal (95% CI)

15
15
36.7 % -1.01 [ -1.77, -0.24 ]
2 calcipotriol vs. white soft parafn + coal tar Tham 1994 27 -2.3 (0.83) 27 -1.2 (0.96) 63.3 % -1.21 [ -1.79, -0.62 ]
Subtotal (95% CI)

27
27
63.3 % -1.21 [ -1.79, -0.62 ]
Total (95% CI)
42
42
100.0 % -1.13 [ -1.60, -0.67 ]
-10
-5
10
Favours coal tar
429
Analysis 11.3. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 3 PASI.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 3 PASI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Coal tar N
Weight
1 calcipotriol vs. coal tar
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 calcipotriol vs. white soft parafn + coal tar Tham 1994
0.0 %
0.0 [ 0.0, 0.0 ]
27
2 (2.1)
27
4.5 (3.6)
100.0 %
-0.84 [ -1.39, -0.28 ]
Subtotal (95% CI)

27
27
100.0 % -0.84 [ -1.39, -0.28 ]
Total (95% CI)

27
27
100.0 % -0.84 [ -1.39, -0.28 ]
-10
-5
10
Favours coal tar
430
Analysis 11.4. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 4 PAGI.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 4 PAGI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Coal tar N
Weight
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 calcipotriol vs. white soft parafn + coal tar Tham 1994
0.0 %
0.0 [ 0.0, 0.0 ]
27
-2.44 (0.89)
27
-1.11 (0.85)
100.0 %
-1.51 [ -2.12, -0.90 ]
Subtotal (95% CI)

27
27
100.0 % -1.51 [ -2.12, -0.90 ]
Total (95% CI)

27
27
100.0 % -1.51 [ -2.12, -0.90 ]
-10
-5
10
Favours coal tar
431
Analysis 11.5. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Coal tar N Mean(SD)
Weight
1 calcipotriol vs. coal tar De Simone 1993 15 -2.7 (0.88) 15 -1.8 (0.86) 36.7 % -1.01 [ -1.77, -0.24 ]
Subtotal (95% CI)

15
15
36.7 % -1.01 [ -1.77, -0.24 ]
2 calcipotriol vs. white soft parafn + coal tar Tham 1994 27 -2.3 (0.83) 27 -1.2 (0.96) 63.3 % -1.21 [ -1.79, -0.62 ]
Subtotal (95% CI)

27
27
63.3 % -1.21 [ -1.79, -0.62 ]
Total (95% CI)
42
42
100.0 % -1.13 [ -1.60, -0.67 ]
-10
-5
10
Favours coal tar
432
Analysis 11.6. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 6 Total withdrawals.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 6 Total withdrawals
Study or subgroup
Coal tar n/N
Weight
Subtotal (95% CI)

Total events: 0 (Vitamin D analogue), 0 (Coal tar) Heterogeneity: not applicable Test for overall effect: not applicable 2 calcipotriol vs. white soft parafn + coal tar Tham 1994
0.0 %
0.0 [ 0.0, 0.0 ]
3/30
3/30
100.0 %
0.0 [ -0.15, 0.15 ]
Subtotal (95% CI)

Total events: 3 (Vitamin D analogue), 3 (Coal tar) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0)
30
30
100.0 %
0.0 [ -0.15, 0.15 ]
Total (95% CI)

30
30
100.0 %
0.0 [ -0.15, 0.15 ]
-1
-0.5
0.5
Favours coal tar
433
Analysis 11.7. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 7 Withdrawals due to adverse events.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Coal tar n/N
Weight
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
1/30
0/30
100.0 %
0.03 [ -0.05, 0.12 ]
Subtotal (95% CI)

30
30
100.0 %
0.03 [ -0.05, 0.12 ]
Total (95% CI)

30
30
100.0 %
0.03 [ -0.05, 0.12 ]
-1
-0.5
0.5
Favours coal tar
434
Analysis 11.8. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 8 Withdrawals due to treatment failure.
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Coal tar n/N
Weight
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/30
0/30
100.0 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
100.0 %
0.0 [ -0.06, 0.06 ]
Total (95% CI)

30
30
100.0 %
0.0 [ -0.06, 0.06 ]
-1
-0.5
0.5
Favours coal tar
435
Analysis 11.10. Comparison 11 Vitamin D analogues vs. coal tar, Outcome 10 Adverse events (systemic).
Comparison: 11 Vitamin D analogues vs. coal tar Outcome: 10 Adverse events (systemic)
Study or subgroup
Coal tar n/N
Weight
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
1/30
1/30
100.0 %
0.0 [ -0.09, 0.09 ]
Subtotal (95% CI)

30
30
100.0 %
0.0 [ -0.09, 0.09 ]
Total (95% CI)

30
30
100.0 %
0.0 [ -0.09, 0.09 ]
-1
-0.5
0.5
Favours coal tar
436
Analysis 12.1. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 1 IAGI.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 1 IAGI Other vitamin D analogue Mean(SD) N Mean(SD) Std. Mean Difference IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Calcipotriol N
Weight
1 Calcipotriol vs. calcitriol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. tacalcitol Veien 1997
0.0 %
0.0 [ 0.0, 0.0 ]
113
-3.8 (0.9)
113
-3.3 (1.2)
53.8 %
-0.47 [ -0.73, -0.21 ]
Subtotal (95% CI)

113
113
53.8 % -0.47 [ -0.73, -0.21 ]
Test for overall effect: Z = 3.48 (P = 0.00050) 3 Calcipotriol vs. maxacalcitol Barker 1999 (H) 26 -3.19 (1.27) 26 -3.73 (1.22) 46.2 % 0.43 [ -0.12, 0.98 ]
Subtotal (95% CI)

26
26
46.2 %
0.43 [ -0.12, 0.98 ]
Total (95% CI)
139
139
100.0 %
-0.06 [ -0.93, 0.82 ]
-10
-5
10
Favours calcipotriol
Favours other vitamin D analogue
437
Analysis 12.2. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 2 TSS.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 2 TSS
Study or subgroup
Calcipotriol N Mean(SD)
Other vitamin D analogue N Mean(SD)
Weight
1 Calcipotriol vs. calcitriol Ortonne 2003 75 1.78 (1.51) 75 0.86 (1.51) 34.2 % 0.61 [ 0.28, 0.93 ]
Subtotal (95% CI)

75
75
34.2 %
0.61 [ 0.28, 0.93 ]
Test for overall effect: Z = 3.63 (P = 0.00029) 2 Calcipotriol vs. tacalcitol Veien 1997 145 -5.05 (2.26) 142 -4.03 (2.26) 35.3 % -0.45 [ -0.68, -0.22 ]
Subtotal (95% CI)

145
142
35.3 % -0.45 [ -0.68, -0.22 ]
Test for overall effect: Z = 3.76 (P = 0.00017) 3 Calcipotriol vs. maxacalcitol Barker 1999 (H) 26 2.8 (2.3) 26 2.4 (3.5) 30.5 % 0.13 [ -0.41, 0.68 ]
Subtotal (95% CI)

26
26
30.5 %
0.13 [ -0.41, 0.68 ]
Total (95% CI)
246
243
100.0 %
0.09 [ -0.65, 0.82 ]
-10
-5
10
438
Analysis 12.3. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 3 PASI.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. calcitriol Bourke 1997 7 4.7 (2.4) 8 8.8 (4.2) 100.0 % -1.11 [ -2.22, 0.01 ]
Subtotal (95% CI)

100.0 % -1.11 [ -2.22, 0.01 ]
Test for overall effect: Z = 1.95 (P = 0.052) 2 Calcipotriol vs. tacalcitol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcipotriol vs. maxacalcitol
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)

100.0 % -1.11 [ -2.22, 0.01 ]
-10
-5
10
439
Analysis 12.5. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. calcitriol Bourke 1997 Ortonne 2003 7 75 4.7 (2.4) 1.78 (1.51) 8 75 8.8 (4.2) 0.86 (1.51) 17.3 % 28.3 % -1.11 [ -2.22, 0.01 ] 0.61 [ 0.28, 0.93 ]
Subtotal (95% CI)
82
83
45.6 %
-0.16 [ -1.83, 1.51 ]
Heterogeneity: Tau?? = 1.29; Chi?? = 8.36, df = 1 (P = 0.004); I?? =88% Test for overall effect: Z = 0.19 (P = 0.85) 2 Calcipotriol vs. tacalcitol Veien 1997 113 -3.8 (0.9) 113 -3.3 (1.2) 28.9 % -0.47 [ -0.73, -0.21 ]
Subtotal (95% CI)

113
113
28.9 % -0.47 [ -0.73, -0.21 ]
Test for overall effect: Z = 3.48 (P = 0.00050) 3 Calcipotriol vs. maxacalcitol Barker 1999 (H) 26 -3.19 (1.27) 26 -3.73 (1.22) 25.5 % 0.43 [ -0.12, 0.98 ]
Subtotal (95% CI)

26
26
25.5 %
0.43 [ -0.12, 0.98 ]
Total (95% CI)
221
222
100.0 %
-0.05 [ -0.76, 0.67 ]
-10
-5
10
440
Analysis 12.6. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 6 Total withdrawals.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 6 Total withdrawals
Study or subgroup
Calcipotriol n/N
Other vitamin D analogue n/N
Weight
1 Calcipotriol vs. calcitriol Bourke 1997 Ortonne 2003 4/12 10/75 4/12 10/75 5.6 % 67.4 % 0.0 [ -0.38, 0.38 ] 0.0 [ -0.11, 0.11 ]
Subtotal (95% CI)
87
87
73.0 %
0.0 [ -0.10, 0.10 ]
Total events: 14 (Calcipotriol), 14 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0) 2 Calcipotriol vs. tacalcitol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcipotriol vs. maxacalcitol Barker 1999 (H)
0.0 %
0.0 [ 0.0, 0.0 ]
Total events: 0 (Calcipotriol), 0 (Other vitamin D analogue)
4/30
4/30
27.0 %
0.0 [ -0.17, 0.17 ]
Subtotal (95% CI)

30
30
27.0 %
0.0 [ -0.17, 0.17 ]
Total (95% CI)
117
117
100.0 %
0.0 [ -0.09, 0.09 ]
Total events: 18 (Calcipotriol), 18 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 2 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
-1
-0.5
0.5
441
Analysis 12.7. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 7 Withdrawals due to adverse events.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. calcitriol Bourke 1997 Ortonne 2003 0/12 9/75 0/12 2/75 19.8 % 36.7 % 0.0 [ -0.15, 0.15 ] 0.09 [ 0.01, 0.18 ]
Subtotal (95% CI)
87
87
56.5 %
0.07 [ -0.02, 0.15 ]
Total events: 9 (Calcipotriol), 2 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.00; Chi?? = 1.23, df = 1 (P = 0.27); I?? =19% Test for overall effect: Z = 1.54 (P = 0.12) 2 Calcipotriol vs. tacalcitol
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/30
0/30
43.5 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
43.5 %
0.0 [ -0.06, 0.06 ]
Total (95% CI)
117
117
100.0 %
0.03 [ -0.05, 0.11 ]
Total events: 9 (Calcipotriol), 2 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.00; Chi?? = 4.77, df = 2 (P = 0.09); I?? =58% Test for overall effect: Z = 0.83 (P = 0.41)
-1
-0.5
0.5
442
Analysis 12.8. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 8 Withdrawals due to treatment failure.
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. calcitriol Bourke 1997 Ortonne 2003 1/12 0/75 2/12 0/75 0.8 % 84.9 % -0.08 [ -0.35, 0.18 ] 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)
87
87
85.7 %
0.00 [ -0.05, 0.05 ]
Total events: 1 (Calcipotriol), 2 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.00; Chi?? = 1.06, df = 1 (P = 0.30); I?? =5% Test for overall effect: Z = 0.12 (P = 0.91) 2 Calcipotriol vs. tacalcitol
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/30
0/30
14.3 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
14.3 %
0.0 [ -0.06, 0.06 ]
Total (95% CI)
117
117
100.0 %
0.00 [ -0.02, 0.02 ]
-1
-0.5
0.5
443
Analysis 12.9. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 9 Adverse events (local).
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 9 Adverse events (local)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. calcitriol Ortonne 2003 8/75 1/75 50.2 % 0.09 [ 0.02, 0.17 ]
Subtotal (95% CI)

75
75
50.2 %
0.09 [ 0.02, 0.17 ]
Total events: 8 (Calcipotriol), 1 (Other vitamin D analogue) Test for overall effect: Z = 2.45 (P = 0.014) 2 Calcipotriol vs. tacalcitol Veien 1997 17/145 18/142 49.8 % -0.01 [ -0.09, 0.07 ]
Subtotal (95% CI)

145
142
49.8 %
-0.01 [ -0.09, 0.07 ]
Total events: 17 (Calcipotriol), 18 (Other vitamin D analogue) Test for overall effect: Z = 0.25 (P = 0.81) 3 Calcipotriol vs. maxacalcitol
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
220
217
100.0 %
0.04 [ -0.06, 0.15 ]
Total events: 25 (Calcipotriol), 19 (Other vitamin D analogue) Heterogeneity: Tau?? = 0.00; Chi?? = 3.99, df = 1 (P = 0.05); I?? =75% Test for overall effect: Z = 0.78 (P = 0.44)
-1
-0.5
0.5
444
Analysis 12.10. Comparison 12 Vitamin D analogue vs. vitamin D analogue, Outcome 10 Adverse events (systemic).
Comparison: 12 Vitamin D analogue vs. vitamin D analogue Outcome: 10 Adverse events (systemic)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. calcitriol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. tacalcitol Veien 1997
0.0 %
0.0 [ 0.0, 0.0 ]
0/142
0/145
95.5 %
0.0 [ -0.01, 0.01 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P = 1.0) 3 Calcipotriol vs. maxacalcitol Barker 1999 (H)
142
145
95.5 %
0.0 [ -0.01, 0.01 ]
0/30
0/30
4.5 %
0.0 [ -0.06, 0.06 ]
Subtotal (95% CI)

30
30
4.5 %
0.0 [ -0.06, 0.06 ]
Total (95% CI)
172
175
100.0 %
0.0 [ -0.01, 0.01 ]
-1
-0.5
0.5
445
Analysis 13.1. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 1 IAGI.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 1 IAGI
Study or subgroup
vitamin D and corticosteroid N Mean(SD)
Weight
1 calcipotriol vs. calcipotriol then cal. OM, BMV ON Ruzicka 1998 86 -3.3 (1.4) 78 -4 (1.23) 10.0 % 0.53 [ 0.22, 0.84 ]
Subtotal (95% CI)

86
78
10.0 % 0.53 [ 0.22, 0.84 ]
Test for overall effect: Z = 3.31 (P = 0.00092) 2 calcipotriol vs. clobetasol propionate then calcipotriol Austad 1998 46 -3.17 (0.82) 46 -3.67 (0.84) 8.4 % 0.60 [ 0.18, 1.02 ]
Subtotal (95% CI)

46
46
8.4 % 0.60 [ 0.18, 1.02 ]
Test for overall effect: Z = 2.80 (P = 0.0051) 3 calcipotriol vs. calcipotriol OM, BMD ON Ortonne 1994 80 -3.6 (1) 74 -4.1 (0.76) 9.9 % 0.56 [ 0.23, 0.88 ]
Subtotal (95% CI)

80
74
9.9 % 0.56 [ 0.23, 0.88 ]
Test for overall effect: Z = 3.39 (P = 0.00070) 4 calcipotriol vs. calcipotriol OM, BMV ON Kragballe 1998b 172 -3 (1.23) 174 -3.3 (1.09) 11.6 % 0.26 [ 0.05, 0.47 ]
Subtotal (95% CI)

172
174
11.6 % 0.26 [ 0.05, 0.47 ]
Test for overall effect: Z = 2.39 (P = 0.017) 5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON Kragballe 1998b 172 -3 (1.23) 172 -3 (1.15) 11.6 % 0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

172
172
11.6 % 0.0 [ -0.21, 0.21 ]
6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-4
-2
Favours vitamin D and corticosteroid
(Continued . . . )
446
(. . .
Study or subgroup Vitamin D analogue N 8 calcipotriol vs. Dovobet BD Douglas 2002 Guenther 2002 (H) Papp 2003 (H) 365 227 308 -3.1 (1.09) -3.3 (1.12) -2.8 (1.21) 369 234 301 -3.7 (0.96) -3.79 (0.97) -3.8 (0.91) 12.5 % 12.0 % 12.2 % Mean(SD) vitamin D and corticosteroid N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
0.58 [ 0.44, 0.73 ] 0.47 [ 0.28, 0.65 ] 0.93 [ 0.76, 1.10 ]
Subtotal (95% CI)
900
904
36.7 % 0.66 [ 0.40, 0.93 ]
Heterogeneity: Tau?? = 0.05; Chi?? = 15.28, df = 2 (P = 0.00048); I?? =87% Test for overall effect: Z = 4.89 (P < 0.00001) 9 calcipotriol vs. Dovobet ON (placebo OM) Guenther 2002 (H) 227 -3.3 (1.12) 150 -3.59 (1) 11.7 % 0.27 [ 0.06, 0.48 ]
Subtotal (95% CI)

227
150
11.7 % 0.27 [ 0.06, 0.48 ]
Test for overall effect: Z = 2.55 (P = 0.011) 10 calcipotriol vs. Dovobet OD
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
1683
1598
100.0 % 0.46 [ 0.27, 0.66 ]
-4
-2
447
Analysis 13.2. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 2 TSS.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 2 TSS
Study or subgroup
Weight
1 calcipotriol vs. calcipotriol then cal. OM, BMV ON
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
2 calcipotriol vs. clobetasol propionate then calcipotriol Austad 1998 46 2.5 (1.3) 46 1.7 (1.2) 8.9 % 0.63 [ 0.21, 1.05 ]
Subtotal (95% CI)

46
46
8.9 % 0.63 [ 0.21, 1.05 ]
Test for overall effect: Z = 2.96 (P = 0.0030) 3 calcipotriol vs. calcipotriol OM, BMD ON
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 4 calcipotriol vs. calcipotriol OM, BMV ON
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 8 calcipotriol vs. Dovobet BD
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
9 calcipotriol vs. Dovobet ON (placebo OM)
Subtotal (95% CI)
0
-4 -2 0 2 4
0.0 %
0.0 [ 0.0, 0.0 ]
(Continued . . . )
448
(. . .
Study or subgroup Vitamin D analogue N Heterogeneity: not applicable Test for overall effect: not applicable 10 calcipotriol vs. Dovobet OD Kaufmann 2002 (H) 480 2.24 (0.9) 490 1.5 (0.9) 91.1 % Mean(SD) vitamin D and corticosteroid N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
0.82 [ 0.69, 0.95 ]
Subtotal (95% CI)

480
490
91.1 % 0.82 [ 0.69, 0.95 ]
Test for overall effect: Z = 12.28 (P < 0.00001) 11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
526
536
100.0 % 0.80 [ 0.68, 0.93 ]
-4
-2
449
Analysis 13.3. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 3 PASI.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 3 PASI
Study or subgroup
Weight
1 calcipotriol vs. calcipotriol then cal. OM, BMV ON Ruzicka 1998 87 1.9 (1.59) 82 1 (0.82) 6.8 % 0.70 [ 0.39, 1.01 ]
Subtotal (95% CI)

87
82
6.8 % 0.70 [ 0.39, 1.01 ]
Test for overall effect: Z = 4.42 (P < 0.00001) 2 calcipotriol vs. clobetasol propionate then calcipotriol
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 calcipotriol vs. calcipotriol OM, BMD ON Ortonne 1994
0.0 %
0.0 [ 0.0, 0.0 ]
81
0.26 (0.22)
75
0.17 (0.16)
6.7 %
0.46 [ 0.14, 0.78 ]
Subtotal (95% CI)

81
75
6.7 % 0.46 [ 0.14, 0.78 ]
Test for overall effect: Z = 2.85 (P = 0.0044) 4 calcipotriol vs. calcipotriol OM, BMV ON Kragballe 1998b 172 4.04 (3.39) 174 3.42 (3.05) 8.2 % 0.19 [ -0.02, 0.40 ]
Subtotal (95% CI)

172
174
8.2 % 0.19 [ -0.02, 0.40 ]
Test for overall effect: Z = 1.78 (P = 0.075) 5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON Kragballe 1998b 172 4.04 (3.39) 172 3.5 (2.86) 8.2 % 0.17 [ -0.04, 0.38 ]
Subtotal (95% CI)

172
172
8.2 % 0.17 [ -0.04, 0.38 ]
Test for overall effect: Z = 1.59 (P = 0.11) 6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON Salmhofer 2000 58 1.9 (1.4) 58 1.8 (1.2) 6.0 % 0.08 [ -0.29, 0.44 ]
Subtotal (95% CI)

58
58
6.0 % 0.08 [ -0.29, 0.44 ]
7 calcipotriol vs. calcipotriol OM, uocinonide acetonide ON Wozel 2001 19 8.94 (5.08) 19 6.3 (4.57) 3.2 % 0.53 [ -0.11, 1.18 ]
Subtotal (95% CI)
19
19
-4 -2 0 2 4
3.2 % 0.53 [ -0.11, 1.18 ]
(Continued . . . )
450
(. . .
Study or subgroup Vitamin D analogue N Heterogeneity: not applicable Test for overall effect: Z = 1.62 (P = 0.11) 8 calcipotriol vs. Dovobet BD Douglas 2002 Guenther 2002 (H) Papp 2003 (H) 332 227 308 4.4 (3.9) 4.2 (3.3) -0.49 (0.32) 342 234 301 2.5 (2.5) 2.7 (2.5) -0.73 (0.25) 8.9 % 8.5 % 8.8 % Mean(SD) vitamin D and corticosteroid N Mean(SD) Std. Mean Difference IV,Random,95% CI Weight
IV,Random,95% CI
0.58 [ 0.43, 0.74 ] 0.51 [ 0.33, 0.70 ] 0.83 [ 0.67, 1.00 ]
Subtotal (95% CI)
867
877
26.3 % 0.64 [ 0.46, 0.83 ]
Heterogeneity: Tau?? = 0.02; Chi?? = 7.59, df = 2 (P = 0.02); I?? =74% Test for overall effect: Z = 6.68 (P < 0.00001) 9 calcipotriol vs. Dovobet ON (placebo OM) Guenther 2002 (H) 227 4.2 (3.3) 150 3 (2.5) 8.2 % 0.40 [ 0.19, 0.61 ]
Subtotal (95% CI)

227
150
8.2 % 0.40 [ 0.19, 0.61 ]
Test for overall effect: Z = 3.75 (P = 0.00018) 10 calcipotriol vs. Dovobet OD Kaufmann 2002 (H) Kragballe 2004 480 327 -0.46 (0.31) -64.1 (18) 490 322 -0.71 (0.26) -73.3 (18) 9.2 % 8.9 % 0.87 [ 0.74, 1.01 ] 0.51 [ 0.35, 0.67 ]
Subtotal (95% CI)
807
812
18.1 % 0.69 [ 0.34, 1.05 ]
Heterogeneity: Tau?? = 0.06; Chi?? = 12.13, df = 1 (P = 0.00050); I?? =92% Test for overall effect: Z = 3.82 (P = 0.00013) 11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) Ortonne 2004 201 -0.38 (0.27) 212 -0.59 (0.27) 8.3 % 0.78 [ 0.58, 0.98 ]
Subtotal (95% CI)

201
212
8.3 % 0.78 [ 0.58, 0.98 ]
Total (95% CI)
2691
2631
100.0 % 0.52 [ 0.38, 0.66 ]
-4
-2
451
Analysis 13.5. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 calcipotriol vs. calcipotriol then cal. OM, BMV ON Ruzicka 1998 86 -3.3 (1.4) 78 -4 (1.23) 6.5 % 0.53 [ 0.22, 0.84 ]
Subtotal (95% CI)

86
78
6.5 % 0.53 [ 0.22, 0.84 ]
Test for overall effect: Z = 3.31 (P = 0.00092) 2 calcipotriol vs. clobetasol propionate then calcipotriol Austad 1998 46 -3.17 (0.82) 46 -3.67 (0.84) 5.4 % 0.60 [ 0.18, 1.02 ]
Subtotal (95% CI)

46
46
5.4 % 0.60 [ 0.18, 1.02 ]
Test for overall effect: Z = 2.80 (P = 0.0051) 3 calcipotriol vs. calcipotriol OM, BMD ON Ortonne 1994 80 -3.6 (1) 74 -4.1 (0.76) 6.4 % 0.56 [ 0.23, 0.88 ]
Subtotal (95% CI)

80
74
6.4 % 0.56 [ 0.23, 0.88 ]
Test for overall effect: Z = 3.39 (P = 0.00070) 4 calcipotriol vs. calcipotriol OM, BMV ON Kragballe 1998b 172 -3 (1.23) 174 -3.3 (1.09) 7.7 % 0.26 [ 0.05, 0.47 ]
Subtotal (95% CI)

172
174
7.7 % 0.26 [ 0.05, 0.47 ]
Test for overall effect: Z = 2.39 (P = 0.017) 5 calcipotriol vs. calcipotriol OM, clobetasone butyrate ON Kragballe 1998b 172 -3 (1.23) 172 -3 (1.15) 7.7 % 0.0 [ -0.21, 0.21 ]
Subtotal (95% CI)

172
172
7.7 %
0.0 [ -0.21, 0.21 ]
6 calcipotriol vs. calcipotriol OM, diucortolone valerate ON Salmhofer 2000 58 1.9 (1.4) 58 1.8 (1.2) 5.9 % 0.08 [ -0.29, 0.44 ]
Subtotal (95% CI)

58
58
5.9 % 0.08 [ -0.29, 0.44 ]
-4
-2
(Continued . . . )
452
(. . .
Study or subgroup Vitamin D analogue N Wozel 2001 19 Mean(SD) 8.94 (5.08) vitamin D and corticosteroid N 19 Mean(SD) 6.3 (4.57) Std. Mean Difference IV,Random,95% CI 3.4 % Weight
IV,Random,95% CI 0.53 [ -0.11, 1.18 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 1.62 (P = 0.11) 8 calcipotriol vs. Dovobet BD Douglas 2002 Guenther 2002 (H) Papp 2003 (H)
19
19
3.4 % 0.53 [ -0.11, 1.18 ]
365 227 308
-3.1 (1.09) -3.3 (1.12) -2.8 (1.21)
369 234 301
-3.7 (0.96) -3.79 (0.97) -3.8 (0.91)
8.4 % 8.0 % 8.2 %
0.58 [ 0.44, 0.73 ] 0.47 [ 0.28, 0.65 ] 0.93 [ 0.76, 1.10 ]
Subtotal (95% CI)
900
904
24.5 % 0.66 [ 0.40, 0.93 ]
Heterogeneity: Tau?? = 0.05; Chi?? = 15.28, df = 2 (P = 0.00048); I?? =87% Test for overall effect: Z = 4.89 (P < 0.00001) 9 calcipotriol vs. Dovobet ON (placebo OM) Guenther 2002 (H) 227 -3.3 (1.12) 150 -3.59 (1) 7.8 % 0.27 [ 0.06, 0.48 ]
Subtotal (95% CI)

227
150
7.8 % 0.27 [ 0.06, 0.48 ]
Test for overall effect: Z = 2.55 (P = 0.011) 10 calcipotriol vs. Dovobet OD Kaufmann 2002 (H) Kragballe 2004 480 327 2.24 (0.9) -64.1 (18) 490 322 1.5 (0.9) -73.3 (18) 8.5 % 8.3 % 0.82 [ 0.69, 0.95 ] 0.51 [ 0.35, 0.67 ]
Subtotal (95% CI)
807
812
16.8 % 0.67 [ 0.36, 0.97 ]
Heterogeneity: Tau?? = 0.04; Chi?? = 8.93, df = 1 (P = 0.003); I?? =89% Test for overall effect: Z = 4.30 (P = 0.000017) 11 Tacalcitol vs. Dovobet ON (4 wks) then calcipotriol ON (4 wks) Ortonne 2004 201 -0.38 (0.27) 212 -0.59 (0.27) 7.8 % 0.78 [ 0.58, 0.98 ]
Subtotal (95% CI)

201
212
7.8 % 0.78 [ 0.58, 0.98 ]
Total (95% CI)
2768
2699
100.0 % 0.50 [ 0.35, 0.65 ]
-4
-2
453
Analysis 13.6. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 6 Total withdrawals.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 6 Total withdrawals
Study or subgroup
vitamin D and corticosteroid n/N
Weight
1 Calcipotriol vs. calcipotriol and corticosteroid Austad 1998 Douglas 2002 Guenther 2002 (H) Kaufmann 2002 (H) Kragballe 1998b Kragballe 2004 Papp 2003 (H) Ruzicka 1998 Salmhofer 2000 Wozel 2001 3/49 37/369 23/231 39/480 19/174 47/327 27/308 5/87 5/63 0/19 3/49 28/372 30/389 13/490 23/351 30/322 16/304 6/82 5/63 0/19 2.5 % 13.6 % 10.3 % 28.3 % 8.0 % 9.2 % 13.9 % 4.1 % 2.5 % 2.4 % 0.0 [ -0.09, 0.09 ] 0.03 [ -0.02, 0.07 ] 0.02 [ -0.02, 0.07 ] 0.05 [ 0.03, 0.08 ] 0.04 [ -0.01, 0.10 ] 0.05 [ 0.00, 0.10 ] 0.04 [ -0.01, 0.08 ] -0.02 [ -0.09, 0.06 ] 0.0 [ -0.09, 0.09 ] 0.0 [ -0.10, 0.10 ]
Subtotal (95% CI)
2107
2441
94.9 %
0.04 [ 0.02, 0.05 ]
Total events: 205 (Vitamin D analogue), 154 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.0; Chi?? = 6.18, df = 9 (P = 0.72); I?? =0.0% Test for overall effect: Z = 4.49 (P < 0.00001) 2 Tacalcitol vs. calcipotriol and corticosteroid Ortonne 2004 51/252 37/249 5.1 % 0.05 [ -0.01, 0.12 ]
Subtotal (95% CI)

252
249
5.1 %
0.05 [ -0.01, 0.12 ]
Total events: 51 (Vitamin D analogue), 37 (vitamin D and corticosteroid)
Total (95% CI)
2359
2690
100.0 %
0.04 [ 0.02, 0.05 ]
Total events: 256 (Vitamin D analogue), 191 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.0; Chi?? = 6.47, df = 10 (P = 0.77); I?? =0.0% Test for overall effect: Z = 4.74 (P < 0.00001)
-0.5
-0.25
0.25
0.5
454
Analysis 13.7. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 7 Withdrawals due to adverse events.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Weight
1 Calcipotriol vs. calcipotriol and corticosteroid Austad 1998 Guenther 2002 (H) Kaufmann 2002 (H) Kragballe 1998b Ortonne 1994 Ruzicka 1998 Salmhofer 2000 Wozel 2001 0/49 6/227 15/480 8/174 6/97 1/87 1/63 0/19 0/49 1/386 3/490 6/351 3/91 1/82 0/63 0/19 6.6 % 21.7 % 34.5 % 8.7 % 2.7 % 9.4 % 5.4 % 1.1 % 0.0 [ -0.04, 0.04 ] 0.02 [ 0.00, 0.05 ] 0.03 [ 0.01, 0.04 ] 0.03 [ -0.01, 0.06 ] 0.03 [ -0.03, 0.09 ] 0.00 [ -0.03, 0.03 ] 0.02 [ -0.03, 0.06 ] 0.0 [ -0.10, 0.10 ]
Subtotal (95% CI)
1196
1531
90.0 %
0.02 [ 0.01, 0.03 ]
Total events: 37 (Vitamin D analogue), 14 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.0; Chi?? = 3.78, df = 7 (P = 0.80); I?? =0.0% Test for overall effect: Z = 3.70 (P = 0.00021) 2 Tacalcitol vs. calcipotriol and corticosteroid Ortonne 2004 11/252 6/249 10.0 % 0.02 [ -0.01, 0.05 ]
Subtotal (95% CI)

252
249
10.0 %
0.02 [ -0.01, 0.05 ]
Total (95% CI)
1448
1780
100.0 %
0.02 [ 0.01, 0.03 ]
Total events: 48 (Vitamin D analogue), 20 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.0; Chi?? = 3.73, df = 8 (P = 0.88); I?? =0.0% Test for overall effect: Z = 3.90 (P = 0.000097)
-0.5
-0.25
0.25
0.5
455
Analysis 13.8. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 8 Withdrawals due to treatment failure.
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Weight
1 Calcipotriol vs. calcipotriol and corticosteroid Austad 1998 Guenther 2002 (H) Kragballe 1998b Salmhofer 2000 Wozel 2001 0/49 2/227 3/174 0/63 0/19 0/49 1/386 2/351 0/63 0/19 12.4 % 29.6 % 23.3 % 16.6 % 2.8 % 0.0 [ -0.04, 0.04 ] 0.01 [ -0.01, 0.02 ] 0.01 [ -0.01, 0.03 ] 0.0 [ -0.03, 0.03 ] 0.0 [ -0.10, 0.10 ]
Subtotal (95% CI)
532
868
84.8 %
0.01 [ 0.00, 0.02 ]
Total events: 5 (Vitamin D analogue), 3 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.0; Chi?? = 0.54, df = 4 (P = 0.97); I?? =0.0% Test for overall effect: Z = 1.23 (P = 0.22) 2 Tacalcitol vs. calcipotriol and corticosteroid Ortonne 2004 16/252 3/249 15.2 % 0.05 [ 0.02, 0.08 ]
Subtotal (95% CI)

252
249
15.2 %
0.05 [ 0.02, 0.08 ]
Total (95% CI)
784
1117
100.0 %
0.01 [ 0.00, 0.03 ]
Total events: 21 (Vitamin D analogue), 6 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.00; Chi?? = 10.57, df = 5 (P = 0.06); I?? =53% Test for overall effect: Z = 1.43 (P = 0.15)
-0.5
-0.25
0.25
0.5
456
Analysis 13.9. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 9 Adverse events (local).
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 9 Adverse events (local)
Study or subgroup
Weight
1 Calcipotriol vs. calcipotriol and corticosteroid Austad 1998 Douglas 2002 Guenther 2002 (H) Kaufmann 2002 (H) Kragballe 1998b Kragballe 2004 Ortonne 1994 Papp 2003 (H) Ruzicka 1998 Salmhofer 2000 Wozel 2001 4/49 44/369 45/227 54/480 54/173 73/327 24/94 53/308 13/87 6/63 1/19 3/49 30/372 40/386 29/490 71/347 35/322 11/88 30/304 6/82 8/63 1/19 3.7 % 15.3 % 9.3 % 19.8 % 5.6 % 10.3 % 3.1 % 11.1 % 4.3 % 3.3 % 2.0 % 0.02 [ -0.08, 0.12 ] 0.04 [ 0.00, 0.08 ] 0.09 [ 0.03, 0.15 ] 0.05 [ 0.02, 0.09 ] 0.11 [ 0.03, 0.19 ] 0.11 [ 0.06, 0.17 ] 0.13 [ 0.02, 0.24 ] 0.07 [ 0.02, 0.13 ] 0.08 [ -0.02, 0.17 ] -0.03 [ -0.14, 0.08 ] 0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)
2196
2522
88.0 %
0.07 [ 0.04, 0.09 ]
Total events: 371 (Vitamin D analogue), 264 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.00; Chi?? = 13.51, df = 10 (P = 0.20); I?? =26% Test for overall effect: Z = 5.57 (P < 0.00001) 2 Tacalcitol vs. calcipotriol and corticosteroid Ortonne 2004 32/252 16/249 12.0 % 0.06 [ 0.01, 0.11 ]
Subtotal (95% CI)

252
249
12.0 %
0.06 [ 0.01, 0.11 ]
Total (95% CI)
2448
2771
100.0 %
0.07 [ 0.05, 0.09 ]
Total events: 403 (Vitamin D analogue), 280 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.00; Chi?? = 13.47, df = 11 (P = 0.26); I?? =18% Test for overall effect: Z = 6.31 (P < 0.00001)
-0.5
-0.25
0.25
0.5
457
Analysis 13.10. Comparison 13 Vitamin D analogue vs. vitamin D and corticosteroid, Outcome 10 Adverse events (systemic).
Comparison: 13 Vitamin D analogue vs. vitamin D and corticosteroid Outcome: 10 Adverse events (systemic)
Study or subgroup
Weight
1 Calcipotriol vs. calcipotriol and corticosteroid Douglas 2002 Papp 2003 (H) Ruzicka 1998 Salmhofer 2000 0/369 0/308 11/87 0/63 0/372 0/304 7/82 0/63 50.8 % 44.2 % 0.5 % 4.4 % 0.0 [ -0.01, 0.01 ] 0.0 [ -0.01, 0.01 ] 0.04 [ -0.05, 0.13 ] 0.0 [ -0.03, 0.03 ]
Subtotal (95% CI)
827
821
100.0 %
0.00 [ -0.01, 0.01 ]
Total events: 11 (Vitamin D analogue), 7 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.00; Chi?? = 4.80, df = 3 (P = 0.19); I?? =38% Test for overall effect: Z = 0.06 (P = 0.95) 2 Tacalcitol vs. calcipotriol and corticosteroid
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Total (95% CI)
827
821
100.0 %
0.00 [ -0.01, 0.01 ]
Total events: 11 (Vitamin D analogue), 7 (vitamin D and corticosteroid) Heterogeneity: Tau?? = 0.00; Chi?? = 4.80, df = 3 (P = 0.19); I?? =38% Test for overall effect: Z = 0.06 (P = 0.95)
-0.5
-0.25
0.25
0.5
458
Analysis 14.1. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 1 IAGI.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 1 IAGI
Study or subgroup
Corticosteroid and salicylic acid N Mean(SD)
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Scarpa 1994 100 -2.72 (1.27) 100 -2.65 (1.18) 100.0 % -0.06 [ -0.33, 0.22 ]
Total (95% CI)

100
100
100.0 %
-0.06 [ -0.33, 0.22 ]
-4
-2
Favours corticosteroid and salicylic acid
Analysis 14.3. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 3 PASI.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 80 2.6 (3.46) 80 2.78 (3.46) 100.0 % -0.05 [ -0.36, 0.26 ]
Total (95% CI)

80
80
100.0 %
-0.05 [ -0.36, 0.26 ]
-4
-2
459
Analysis 14.4. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 4 PAGI.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 4 PAGI
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Scarpa 1994 89 -3.29 (0.73) 97 -2.87 (0.94) 100.0 % -0.49 [ -0.79, -0.20 ]
Total (95% CI)

89
97
100.0 % -0.49 [ -0.79, -0.20 ]
-4
-2
Analysis 14.5. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 Scarpa 1994 80 100 2.6 (3.46) -2.72 (1.27) 80 100 2.78 (3.46) -2.65 (1.18) 44.4 % 55.6 % -0.05 [ -0.36, 0.26 ] -0.06 [ -0.33, 0.22 ]
Total (95% CI)
180
180
100.0 %
-0.05 [ -0.26, 0.15 ]
-4
-2
460
Analysis 14.6. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 6 Total withdrawals.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 6 Total withdrawals
Study or subgroup
Calcipotriol n/N
Corticosteroid and salicylic acid n/N
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 Tosti 1998 20/80 6/29 17/80 8/29 73.9 % 26.1 % 0.04 [ -0.09, 0.17 ] -0.07 [ -0.29, 0.15 ]
Total (95% CI)
109
109
100.0 %
0.01 [ -0.10, 0.12 ]
Total events: 26 (Calcipotriol), 25 (Corticosteroid and salicylic acid) Heterogeneity: Tau?? = 0.0; Chi?? = 0.67, df = 1 (P = 0.41); I?? =0.0% Test for overall effect: Z = 0.17 (P = 0.87)
-1
-0.5
0.5
Analysis 14.7. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 7 Withdrawals due to adverse events.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 4/80 0/80 100.0 % 0.05 [ 0.00, 0.10 ]
Total (95% CI)

80
80
100.0 %
0.05 [ 0.00, 0.10 ]
Total events: 4 (Calcipotriol), 0 (Corticosteroid and salicylic acid) Test for overall effect: Z = 1.86 (P = 0.063)
-1
-0.5
0.5
461
Analysis 14.8. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 8 Withdrawals due to treatment failure.
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 1/80 3/80 100.0 % -0.02 [ -0.07, 0.02 ]
Total (95% CI)

80
80
100.0 %
-0.02 [ -0.07, 0.02 ]
-1
-0.5
0.5
Analysis 14.9. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 9 Adverse events (local).
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 9 Adverse events (local)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 Tosti 1998 7/80 3/29 0/80 3/29 81.1 % 18.9 % 0.09 [ 0.02, 0.15 ] 0.0 [ -0.16, 0.16 ]
Total (95% CI)
109
109
100.0 %
0.07 [ 0.00, 0.14 ]
Total events: 10 (Calcipotriol), 3 (Corticosteroid and salicylic acid) Heterogeneity: Tau?? = 0.00; Chi?? = 1.13, df = 1 (P = 0.29); I?? =12% Test for overall effect: Z = 1.97 (P = 0.049)
-1
-0.5
0.5
462
Analysis 14.10. Comparison 14 Calcipotriol vs. corticosteroid and salicylic acid, Outcome 10 Adverse events (systemic).
Comparison: 14 Calcipotriol vs. corticosteroid and salicylic acid Outcome: 10 Adverse events (systemic)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. betamethasone dipropionate + salicylic acid Crosti 1997 0/80 0/80 100.0 % 0.0 [ -0.02, 0.02 ]
Total (95% CI)

80
80
100.0 %
0.0 [ -0.02, 0.02 ]
-0.5
-0.25
0.25
0.5
463
Analysis 15.1. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 1 IAGI.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 1 IAGI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Coal tar polytherapy N
Weight
1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ??) Klaber 2000b 208 -2.77 (1.28) 209 -2.07 (1.56) 67.1 % -0.49 [ -0.68, -0.29 ]
Subtotal (95% CI)

208
209
67.1 % -0.49 [ -0.68, -0.29 ]
Test for overall effect: Z = 4.92 (P < 0.00001) 2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream Pinheiro 1997 65 -2.66 (0.67) 57 -2.28 (0.92) 19.6 % -0.47 [ -0.83, -0.11 ]
Subtotal (95% CI)

65
57
19.6 % -0.47 [ -0.83, -0.11 ]
Test for overall effect: Z = 2.58 (P = 0.010) 3 Calcipotriol vs. dithranol / tar regimen van de Kerkhof 2002a 41 -3.41 (1.2) 46 -2.48 (1.24) 13.4 % -0.75 [ -1.19, -0.32 ]
Subtotal (95% CI)

41
46
13.4 % -0.75 [ -1.19, -0.32 ]
Total (95% CI)
314
312
100.0 % -0.52 [ -0.68, -0.36 ]
-4
-2
Favours coal tar polytherapy
464
Analysis 15.2. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 2 TSS.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 2 TSS
Study or subgroup
Coal tar polytherapy N Mean(SD)
Weight
1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ??) Klaber 2000b 210 3.1 (2) 210 3.7 (2.2) 40.7 % -0.28 [ -0.48, -0.09 ]
Subtotal (95% CI)

210
210
40.7 % -0.28 [ -0.48, -0.09 ]
Test for overall effect: Z = 2.90 (P = 0.0037) 2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream Pinheiro 1997 69 2.7 (2.18) 63 3.8 (2.18) 32.3 % -0.50 [ -0.85, -0.15 ]
Subtotal (95% CI)

69
63
32.3 % -0.50 [ -0.85, -0.15 ]
Subtotal (95% CI)

41
46
27.0 % -0.95 [ -1.40, -0.51 ]
Total (95% CI)
320
319
100.0 % -0.54 [ -0.90, -0.18 ]
-4
-2
465
Analysis 15.3. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 3 PASI.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ??)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
3 Calcipotriol vs. dithranol / tar regimen van de Kerkhof 2002a 41 -57.4 (28.9) 46 -36.1 (36.4) 100.0 % -0.64 [ -1.07, -0.21 ]
Subtotal (95% CI)

41
46
100.0 % -0.64 [ -1.07, -0.21 ]
Total (95% CI)

41
46
100.0 % -0.64 [ -1.07, -0.21 ]
-4
-2
466
Analysis 15.4. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 4 PAGI.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 4 PAGI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Coal tar polytherapy N
Weight
1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ??)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
3 Calcipotriol vs. dithranol / tar regimen van de Kerkhof 2002a 41 -3.29 (1.19) 46 -2.57 (1.36) 100.0 % -0.56 [ -0.99, -0.13 ]
Subtotal (95% CI)

41
46
100.0 % -0.56 [ -0.99, -0.13 ]
Total (95% CI)

41
46
100.0 % -0.56 [ -0.99, -0.13 ]
-4
-2
467
Analysis 15.5. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. coal tar,1%, coconut oil, 1%, salicylic acid, 0.5%, shampoo (Capasal ??) Klaber 2000b 208 -2.77 (1.28) 209 -2.07 (1.56) 67.1 % -0.49 [ -0.68, -0.29 ]
Subtotal (95% CI)

208
209
67.1 % -0.49 [ -0.68, -0.29 ]
Test for overall effect: Z = 4.92 (P < 0.00001) 2 Calcipotriol vs. coal tar + allantoin + hydrocortisone cream Pinheiro 1997 65 -2.66 (0.67) 57 -2.28 (0.92) 19.6 % -0.47 [ -0.83, -0.11 ]
Subtotal (95% CI)

65
57
19.6 % -0.47 [ -0.83, -0.11 ]
Subtotal (95% CI)

41
46
13.4 % -0.75 [ -1.19, -0.32 ]
Total (95% CI)
314
312
100.0 % -0.52 [ -0.68, -0.36 ]
-4
-2
468
Analysis 15.6. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 6 Total withdrawals.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 6 Total withdrawals
Study or subgroup
Calcipotriol n/N
Coal tar polytherapy n/N
Weight
1 Calcipotriol vs. coal tar polytherapy (any) Klaber 2000b Pinheiro 1997 van de Kerkhof 2002a 72/238 4/69 3/41 69/237 6/63 4/47 42.6 % 34.7 % 22.6 % 0.01 [ -0.07, 0.09 ] -0.04 [ -0.13, 0.05 ] -0.01 [ -0.12, 0.10 ]
Total (95% CI)
348
347
100.0 %
-0.01 [ -0.06, 0.04 ]
Total events: 79 (Calcipotriol), 79 (Coal tar polytherapy) Heterogeneity: Tau?? = 0.0; Chi?? = 0.74, df = 2 (P = 0.69); I?? =0.0% Test for overall effect: Z = 0.39 (P = 0.69)
-1
-0.5
0.5
469
Analysis 15.7. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 7 Withdrawals due to adverse events.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. coal tar polytherapy (any) Klaber 2000b Pinheiro 1997 van de Kerkhof 2002a 35/230 1/65 2/41 16/215 3/57 2/47 36.2 % 34.5 % 29.3 % 0.08 [ 0.02, 0.14 ] -0.04 [ -0.10, 0.03 ] 0.01 [ -0.08, 0.09 ]
Total (95% CI)
336
319
100.0 %
0.02 [ -0.06, 0.10 ]
Total events: 38 (Calcipotriol), 21 (Coal tar polytherapy) Heterogeneity: Tau?? = 0.00; Chi?? = 8.29, df = 2 (P = 0.02); I?? =76% Test for overall effect: Z = 0.41 (P = 0.68)
-1
-0.5
0.5
Analysis 15.8. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 8 Withdrawals due to treatment failure.
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. coal tar polytherapy (any) van de Kerkhof 2002a 1/41 1/47 100.0 % 0.00 [ -0.06, 0.07 ]
Total (95% CI)

41
47
100.0 %
0.00 [ -0.06, 0.07 ]
Total events: 1 (Calcipotriol), 1 (Coal tar polytherapy) Test for overall effect: Z = 0.10 (P = 0.92)
-1
-0.5
0.5
470
Analysis 15.9. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 9 Adverse events (local).
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 9 Adverse events (local)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. coal tar polytherapy (any) Klaber 2000b Pinheiro 1997 137/230 15/65 77/215 10/57 54.6 % 45.4 % 0.24 [ 0.15, 0.33 ] 0.06 [ -0.09, 0.20 ]
Total (95% CI)
295
272
100.0 %
0.15 [ -0.03, 0.33 ]
Total events: 152 (Calcipotriol), 87 (Coal tar polytherapy) Heterogeneity: Tau?? = 0.01; Chi?? = 4.61, df = 1 (P = 0.03); I?? =78% Test for overall effect: Z = 1.69 (P = 0.092)
-1
-0.5
0.5
471
Analysis 15.10. Comparison 15 Calcipotriol vs. coal tar polytherapy, Outcome 10 Adverse events (systemic).
Comparison: 15 Calcipotriol vs. coal tar polytherapy Outcome: 10 Adverse events (systemic)
Study or subgroup
Calcipotriol n/N
Weight
1 Calcipotriol vs. coal tar polytherapy (any) Klaber 2000b van de Kerkhof 2002a 0/230 0/41 0/215 0/47 96.1 % 3.9 % 0.0 [ -0.01, 0.01 ] 0.0 [ -0.04, 0.04 ]
Total (95% CI)
271
262
100.0 %
0.0 [ -0.01, 0.01 ]
Total events: 0 (Calcipotriol), 0 (Coal tar polytherapy) Heterogeneity: Tau?? = 0.0; Chi?? = 0.0, df = 1 (P = 1.00); I?? =0.0% Test for overall effect: Z = 0.0 (P = 1.0)
-0.2
-0.1
0.1
0.2
472
Analysis 16.1. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 1 IAGI.

Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 1 IAGI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Calcipotriol BD N Mean(SD)
Calcipotriol OD N
Weight
1 Calcipotriol BD vs. calcipotriol OD
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
2 Calcipotriol BD vs. calcipotriol OM, vehicle ON Kragballe 1998b 172 -2.98 (1.23) 172 -2.63 (1.34) 100.0 % -0.27 [ -0.48, -0.06 ]
Subtotal (95% CI)

172
172
100.0 % -0.27 [ -0.48, -0.06 ]
Total (95% CI)

172
172
100.0 % -0.27 [ -0.48, -0.06 ]
-4
-2
Favours calcipotriol BD
Favours calcipotriol OD
473
Analysis 16.3. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 3 PASI.

Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 3 PASI Std. Mean Difference Mean(SD) IV,Random,95% CI Std. Mean Difference IV,Random,95% CI
Study or subgroup
Calcipotriol OD N
Weight
1 Calcipotriol BD vs. calcipotriol OD Baiocchi 1997 130 0.97 (1.3) 130 1.1 (1.4) 43.0 % -0.10 [ -0.34, 0.15 ]
Subtotal (95% CI)

130
130
43.0 % -0.10 [ -0.34, 0.15 ]
Test for overall effect: Z = 0.77 (P = 0.44) 2 Calcipotriol BD vs. calcipotriol OM, vehicle ON Kragballe 1998b 172 4.04 (3.39) 173 4.58 (3.93) 57.0 % -0.15 [ -0.36, 0.06 ]
Subtotal (95% CI)

172
173
57.0 % -0.15 [ -0.36, 0.06 ]
Total (95% CI)
302
303
100.0 % -0.12 [ -0.28, 0.03 ]
-4
-2
474
Analysis 16.5. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Calcipotriol OD N Mean(SD)
Weight
1 Calcipotriol BD vs. calcipotriol OD Baiocchi 1997 130 0.97 (1.3) 130 1.1 (1.4) 44.1 % -0.10 [ -0.34, 0.15 ]
Subtotal (95% CI)

130
130
44.1 % -0.10 [ -0.34, 0.15 ]
Test for overall effect: Z = 0.77 (P = 0.44) 2 Calcipotriol BD vs. calcipotriol OM, vehicle ON Kragballe 1998b 172 -2.98 (1.23) 172 -2.63 (1.34) 55.9 % -0.27 [ -0.48, -0.06 ]
Subtotal (95% CI)

172
172
55.9 % -0.27 [ -0.48, -0.06 ]
Total (95% CI)
302
302
100.0 % -0.19 [ -0.37, -0.02 ]
-4
-2
475
Analysis 16.6. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 6 Total withdrawals.

Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 6 Total withdrawals
Study or subgroup
Calcipotriol BD n/N
Calcipotriol OD n/N 34/132 17/174
Weight
Risk Difference MH,Random,95% CI -0.01 [ -0.11, 0.10 ] 0.01 [ -0.05, 0.08 ]
Baiocchi 1997 Kragballe 1998b
33/132 19/174
27.1 % 72.9 %
Total (95% CI)
306
306
100.0 %
0.01 [ -0.05, 0.06 ]
Total events: 52 (Calcipotriol BD), 51 (Calcipotriol OD) Heterogeneity: Tau?? = 0.0; Chi?? = 0.10, df = 1 (P = 0.75); I?? =0.0% Test for overall effect: Z = 0.23 (P = 0.82)
-1
-0.5
0.5
Analysis 16.7. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 7 Withdrawals due to adverse events.
Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Calcipotriol BD n/N
Weight
7/132 8/174
38.5 % 61.5 %
Total (95% CI)
306
306
100.0 %
0.01 [ -0.02, 0.04 ]
-0.5
-0.25
0.25
0.5
476
Analysis 16.8. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 8 Withdrawals due to treatment failure.
Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Calcipotriol BD n/N
Weight
1/132 3/174
63.1 % 36.9 %
Total (95% CI)
306
306
100.0 %
0.0 [ -0.02, 0.02 ]
-0.5
-0.25
0.25
0.5
Analysis 16.9. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 9 Adverse events (local).
Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 9 Adverse events (local)
Study or subgroup
Calcipotriol BD n/N
Calcipotriol OD n/N 59/172
Weight
Risk Difference MH,Random,95% CI -0.03 [ -0.13, 0.07 ]
Kragballe 1998b
54/173
100.0 %
Total (95% CI)

173
172
100.0 %
-0.03 [ -0.13, 0.07 ]
Total events: 54 (Calcipotriol BD), 59 (Calcipotriol OD) Test for overall effect: Z = 0.61 (P = 0.54)
-1
-0.5
0.5
477
Analysis 16.10. Comparison 16 Head-to-head calcipotriol: Dosing, Outcome 10 Adverse events (systemic).
Comparison: 16 Head-to-head calcipotriol: Dosing Outcome: 10 Adverse events (systemic)
Study or subgroup
Calcipotriol BD n/N
Calcipotriol OD n/N 0/132
Weight
Baiocchi 1997
0/132
100.0 %
Total (95% CI)

132
132
100.0 %
0.0 [ -0.01, 0.01 ]
Total events: 0 (Calcipotriol BD), 0 (Calcipotriol OD)
-0.5
-0.25
0.25
0.5
Analysis 17.2. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 2 TSS.

Comparison: 17 Head-to-head calcipotriol: Occlusion Outcome: 2 TSS
Study or subgroup
Calcipotriol plus occlusion N Mean(SD)
Weight
1 Calcipotriol BD vs. calcipotriol BD + occlusion ON Bourke 1993b 19 -3.1 (2.6) 19 -5.2 (2.6) 100.0 % 0.79 [ 0.13, 1.45 ]
Total (95% CI)

19
19
100.0 %
0.79 [ 0.13, 1.45 ]
-4
-2
Favours calcipotriol plus occlusion
478
Analysis 17.5. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 17 Head-to-head calcipotriol: Occlusion Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Calcipotriol plus occlusion N Mean(SD)
Weight
1 Calcipotriol BD vs. calcipotriol BD + occlusion ON Bourke 1993b 19 -3.1 (2.6) 19 -5.2 (2.6) 100.0 % 0.79 [ 0.13, 1.45 ]
Total (95% CI)

19
19
100.0 %
0.79 [ 0.13, 1.45 ]
-4
-2
Analysis 17.10. Comparison 17 Head-to-head calcipotriol: Occlusion, Outcome 10 Adverse events (systemic).
Comparison: 17 Head-to-head calcipotriol: Occlusion Outcome: 10 Adverse events (systemic)
Study or subgroup
Calcipotriol n/N
Calcipotriol plus occlusion n/N 0/19
Weight
Bourke 1993b
0/19
100.0 %
Total (95% CI)

19
19
100.0 %
0.0 [ -0.10, 0.10 ]
Total events: 0 (Calcipotriol), 0 (Calcipotriol plus occlusion) Test for overall effect: Z = 0.0 (P = 1.0)
-1
-0.5
0.5
479
Analysis 18.1. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 1 IAGI.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 1 IAGI
Study or subgroup
Weight
1 Calcipotriol vs. propylthiouracil cream
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. tacrolimus ointment
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcipotriol vs. tazarotene
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Calcipotriol vs. vitamin B12 cream Stuecker 2001
0.0 %
0.0 [ 0.0, 0.0 ]
13 -2.08 (0.49)
13
-1.77 (0.6)
100.0 %
-0.55 [ -1.33, 0.24 ]
Subtotal (95% CI)

13
13
100.0 % -0.55 [ -1.33, 0.24 ]
6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-4
-2
480
Analysis 18.2. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 2 TSS.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 2 TSS
Study or subgroup
Weight
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. tacrolimus ointment Zonneveld 1998 (H)
0.0 %
0.0 [ 0.0, 0.0 ]
23
2.6 (2.18)
24
4.7 (2.18)
100.0 %
-0.95 [ -1.55, -0.34 ]
Subtotal (95% CI)

23
24
100.0 % -0.95 [ -1.55, -0.34 ]
Test for overall effect: Z = 3.06 (P = 0.0022) 3 Calcipotriol vs. tazarotene Han 2001 101 3.91 (6.08) 98 4.18 (4.39) 100.0 % -0.05 [ -0.33, 0.23 ]
Subtotal (95% CI)

101
98
100.0 % -0.05 [ -0.33, 0.23 ]
Test for overall effect: Z = 0.36 (P = 0.72) 4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Calcipotriol vs. vitamin B12 cream
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-10
-5
10
481
Analysis 18.3. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 3 PASI.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 3 PASI
Study or subgroup
Weight
1 Calcipotriol vs. propylthiouracil cream Sanchez 2001 14 1.11 (1.04) 13 3.83 (1.31) 100.0 % -2.24 [ -3.23, -1.25 ]
Subtotal (95% CI)

14
13
100.0 % -2.24 [ -3.23, -1.25 ]
Test for overall effect: Z = 4.42 (P < 0.00001) 2 Calcipotriol vs. tacrolimus ointment
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
13
0.8 (0.7)
13
0.81 (0.7)
100.0 %
-0.01 [ -0.78, 0.75 ]
Subtotal (95% CI)

13
13
100.0 % -0.01 [ -0.78, 0.75 ]
6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) Kragballe 2004 327 -64.1 (18) 323 -68.2 (18) 100.0 % 0.23 [ 0.07, 0.38 ]
Subtotal (95% CI)

327
323
100.0 %
0.23 [ 0.07, 0.38 ]
Test for overall effect: Z = 2.89 (P = 0.0038) 7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 201 -38.4 (26.5) 212 -59 (26.5) 100.0 % 0.78 [ 0.58, 0.98 ]
Subtotal (95% CI)

201
212
100.0 %
0.78 [ 0.58, 0.98 ]
-4
-2
482
Analysis 18.4. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 4 PAGI.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 4 PAGI
Study or subgroup
Weight
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 2 Calcipotriol vs. tacrolimus ointment
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
13 -2.08 (0.49)
13
-1.77 (0.6)
100.0 %
-0.55 [ -1.33, 0.24 ]
Subtotal (95% CI)

13
13
100.0 % -0.55 [ -1.33, 0.24 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-4
-2
483
Analysis 18.5. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 5 Combined endpoint (IAGI/TSS/PASI/PAGI).
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 5 Combined endpoint (IAGI/TSS/PASI/PAGI)
Study or subgroup
Weight
1 Calcipotriol vs. propylthiouracil cream Sanchez 2001 14 1.11 (1.04) 13 3.83 (1.31) 100.0 % -2.24 [ -3.23, -1.25 ]
Subtotal (95% CI)

14
13
100.0 % -2.24 [ -3.23, -1.25 ]
Test for overall effect: Z = 4.42 (P < 0.00001) 2 Calcipotriol vs. tacrolimus ointment Zonneveld 1998 (H) 23 2.6 (2.18) 24 4.7 (2.18) 100.0 % -0.95 [ -1.55, -0.34 ]
Subtotal (95% CI)

23
24
100.0 % -0.95 [ -1.55, -0.34 ]
Test for overall effect: Z = 3.06 (P = 0.0022) 3 Calcipotriol vs. tazarotene Han 2001 101 3.91 (6.08) 98 4.18 (4.39) 100.0 % -0.05 [ -0.33, 0.23 ]
Subtotal (95% CI)

101
98
100.0 % -0.05 [ -0.33, 0.23 ]
Test for overall effect: Z = 0.36 (P = 0.72) 4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
13 -2.08 (0.49)
13
-1.77 (0.6)
100.0 %
-0.55 [ -1.33, 0.24 ]
Subtotal (95% CI)

13
13
100.0 % -0.55 [ -1.33, 0.24 ]
6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) Kragballe 2004 327 -64.1 (18) 323 -68.2 (18) 100.0 % 0.23 [ 0.07, 0.38 ]
Subtotal (95% CI)

327
323
100.0 %
0.23 [ 0.07, 0.38 ]
Test for overall effect: Z = 2.89 (P = 0.0038) 7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 201 -38.4 (26.5) 212 -59 (26.5) 100.0 % 0.78 [ 0.58, 0.98 ]
Subtotal (95% CI)

201
212
100.0 %
0.78 [ 0.58, 0.98 ]
-4
-2
484
Analysis 18.6. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 6 Total withdrawals.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 6 Total withdrawals
Study or subgroup
Other treatment n/N
Weight
1 Calcipotriol vs. Propylthiouracil cream Sanchez 2001 2/14 1/14 100.0 % 0.07 [ -0.16, 0.30 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.62 (P = 0.54) 2 Calcipotriol vs. tacrolimus ointment
14
14
100.0 %
0.07 [ -0.16, 0.30 ]
Total events: 2 (Vitamin D analogue), 1 (Other treatment)
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 3 Calcipotriol vs. tazarotene Han 2001
0.0 %
0.0 [ 0.0, 0.0 ]
2/103
7/105
100.0 %
-0.05 [ -0.10, 0.01 ]
Subtotal (95% CI)

103
105
100.0 %
-0.05 [ -0.10, 0.01 ]
4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream Guenther 2000 6/60 8/60 100.0 % -0.03 [ -0.15, 0.08 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: Z = 0.57 (P = 0.57) 5 Calcipotriol vs. vitamin B12 cream Stuecker 2001
60
60
100.0 %
-0.03 [ -0.15, 0.08 ]
0/13
0/13
100.0 %
0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)

13
13
100.0 %
0.0 [ -0.14, 0.14 ]
6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) Kragballe 2004 47/327 21/322
-1 -0.5 0 0.5 1
100.0 %
0.08 [ 0.03, 0.13 ]
(Continued . . . )
485
(. . .
Study or subgroup Vitamin D analogue n/N Other treatment n/N Risk Difference MH,Random,95% CI Weight
Continued)
Subtotal (95% CI)

327
322
100.0 %
0.08 [ 0.03, 0.13 ]
7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 51/252 37/249 100.0 % 0.05 [ -0.01, 0.12 ]
Subtotal (95% CI)

252
249
100.0 %
0.05 [ -0.01, 0.12 ]
-1
-0.5
0.5
Analysis 18.7. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 7 Withdrawals due to adverse events.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 7 Withdrawals due to adverse events
Study or subgroup
Other treatment n/N
Weight
Subtotal (95% CI)

14
14
100.0 %
0.07 [ -0.16, 0.30 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
(Continued . . . )
486
(. . .
Study or subgroup Vitamin D analogue n/N Test for overall effect: not applicable 3 Calcipotriol vs. tazarotene Han 2001 3/103 5/105 100.0 % Other treatment n/N Risk Difference MH,Random,95% CI Weight
Continued)
-0.02 [ -0.07, 0.03 ]
Subtotal (95% CI)

103
105
100.0 %
-0.02 [ -0.07, 0.03 ]
4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream Guenther 2000 3/60 4/60 100.0 % -0.02 [ -0.10, 0.07 ]
Subtotal (95% CI)

60
60
100.0 %
-0.02 [ -0.10, 0.07 ]
0/13
0/13
100.0 %
0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)

13
13
100.0 %
0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 11/252 6/249 100.0 % 0.02 [ -0.01, 0.05 ]
Subtotal (95% CI)

252
249
100.0 %
0.02 [ -0.01, 0.05 ]
-1
-0.5
0.5
487
Analysis 18.8. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 8 Withdrawals due to treatment failure.
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 8 Withdrawals due to treatment failure
Study or subgroup
Other treatment n/N
Weight
1 Calcipotriol vs. Propylthiouracil cream Sanchez 2001 0/14 1/14 100.0 % -0.07 [ -0.25, 0.11 ]
Subtotal (95% CI)

14
14
100.0 %
-0.07 [ -0.25, 0.11 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
0/103
0/105
100.0 %
0.0 [ -0.02, 0.02 ]
Subtotal (95% CI)

103
105
100.0 %
0.0 [ -0.02, 0.02 ]
4 Calcipotriol vs. tazarotene gel plus mometasone furoate cream Guenther 2000 1/60 1/60 100.0 % 0.0 [ -0.05, 0.05 ]
Subtotal (95% CI)

60
60
100.0 %
0.0 [ -0.05, 0.05 ]
0/13
0/13
100.0 %
0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)

13
13
100.0 %
0.0 [ -0.14, 0.14 ]
Subtotal (95% CI)
0.0 %
0.0 [ 0.0, 0.0 ]
-1
-0.5
0.5
(Continued . . . )
488
(. . .
Study or subgroup Vitamin D analogue n/N Heterogeneity: not applicable Test for overall effect: not applicable 7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 16/252 3/249 100.0 % Other treatment n/N Risk Difference MH,Random,95% CI Weight
Continued)
0.05 [ 0.02, 0.08 ]
Subtotal (95% CI)

252
249
100.0 %
0.05 [ 0.02, 0.08 ]
-1
-0.5
0.5
Analysis 18.9. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 9 Adverse events (local).
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 9 Adverse events (local)
Study or subgroup
Other treatment n/N
Weight
1 Calcipotriol vs. Propylthiouracil cream Sanchez 2001 0/14 1/14 100.0 % -0.07 [ -0.25, 0.11 ]
Subtotal (95% CI)

14
14
100.0 %
-0.07 [ -0.25, 0.11 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
10/101
13/103
-1 -0.5 0 0.5 1
100.0 %
-0.03 [ -0.11, 0.06 ]
(Continued . . . )
489
(. . .
Continued)
Subtotal (95% CI)

101
103
100.0 %
-0.03 [ -0.11, 0.06 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
4/13
1/13
100.0 %
0.23 [ -0.06, 0.52 ]
Subtotal (95% CI)

13
13
100.0 %
0.23 [ -0.06, 0.52 ]
6 Calcipotriol vs. Dovobet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (8 wks) Kragballe 2004 73/327 37/322 100.0 % 0.11 [ 0.05, 0.17 ]
Subtotal (95% CI)

327
322
100.0 %
0.11 [ 0.05, 0.17 ]
7 Tacalcitol vs. calcipotriol (4 wks) then Dovobet (4 wks) Ortonne 2004 32/252 16/249 100.0 % 0.06 [ 0.01, 0.11 ]
Subtotal (95% CI)

252
249
100.0 %
0.06 [ 0.01, 0.11 ]
-1
-0.5
0.5
490
Analysis 18.10. Comparison 18 Vitamin D analogues vs. other treatment, Outcome 10 Adverse events (systemic).
Comparison: 18 Vitamin D analogues vs. other treatment Outcome: 10 Adverse events (systemic)
Study or subgroup
Other treatment n/N
Weight
Subtotal (95% CI)

14
14
100.0 %
0.0 [ -0.13, 0.13 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
1/92
2/91
100.0 %
-0.01 [ -0.05, 0.03 ]
Subtotal (95% CI)

92
91
100.0 %
-0.01 [ -0.05, 0.03 ]
Subtotal (95% CI)

Heterogeneity: not applicable Test for overall effect: not applicable 5 Calcipotriol vs. vitamin B12 cream
0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-0.5
-0.25
0.25
0.5
(Continued . . . )
491
(. . .
Continued)
Subtotal (95% CI)

0.0 %
0.0 [ 0.0, 0.0 ]
-0.5
-0.25
0.25
0.5
ADDITIONAL TABLES
Table 1. List of acronyms
Acronym BC BD BMD BMV BSA CI EQ-5D FU IAGI I LF MEMS NA NR
Full name Baseline comparability demonstrated (clinical / demographic) twice daily betamethasone dipropionate betamethasone valerate Body Surface Area condence interval EuroQol follow up (includes treatment period) investigator assessment of global improvement heterogeneity statistic loss to follow up (% patients randomised, not contributing to primary outcome measure) Medication Event Monitoring System not available / not applicable not reported
492
Table 1. List of acronyms
(Continued)
OD OM ON PAGI PASI PDI PMAQ-3w pt QOL RD SMD TCP TD TSS UV VDRE wks
once daily once in the morning once at night patient assessment of global improvement Psoriasis Area Severity Index Psoriasis Disability Index Medication Adherence Questionnaire, version 3W point quality of life risk difference standardised mean difference Two compound product treatment duration total severity score ultra violet Vitamin D-Responsive Element weeks
Table 2. Overview of outcome measures on effectiveness Outcome Acronym Construct Scale, minimum Scale, maximum 7 pt Notes Calculated means and standard deviations by assigning zero to worse (or equivalent). Higher scores indicate greater improvement
* Investigators as- IAGI sessment of overall global improvement
Improvement 4 pt from baseline variably dened. Common taxonomy ranges from worse to cleared
493
Table 2. Overview of outcome measures on effectiveness
(Continued)
Total Severity Score TSS
Redness (ery- 0 to 3 thema), thickness (inltration) and scaling (sometimes also itching (pruritis)) of target plaque(s).Scored separately then summed
0 to 24
Also known as the Local Psoriasis Severity Index or the Total Sum ScoreHigher scores indicate more severe disease
Psoriasis Area and PASI Severity Index
redness, thickness, and 0 to 68 (without head) 0 to 72 (including Higher scores indicate scaliness of the lesions head) more severe disease (each graded on a 0 to 4 scale), weighted by the area of involvement (0 to 6) and summed Assessed as IAGI 4 pt 7 pt Less often reported than IAGI. Majority of included trials use 5 pt scale
* Patients PAGI assessment of overall global improvement
* IAGI /PAGI data are entered as a negative values, thus a reduction denotes a positive improvement for the active treatment consistent with TSS and PASI measures Table 3. Summary of imputed standard deviation values
Type of study/ Placebo, IAGI score Between-patient (endpoint) Within-patient (endpoint) All (endpoint) Between-patient (change) Within-patient (change) Within-patient (% change) 1.09
Placebo, TSS
Placebo, PASI
H2H, IAGI
H2H, TSS
H2H, PASI
1.26
3.66
1.10
1.67
3.46
1.02
1.47
7.89
0.96
1.51
2.58
1.08 NA
1.40 1.46
4.30 5.48
1.09 NA
1.66 1.74
3.28 7.85
NA
1.58
NA
NA
1.96
NA
NA
0.18
NA
NA
NA
NA
494
Table 3. Summary of imputed standard deviation values
(Continued)
Between-patient (% change)
NA
NA
0.30
NA
NA
0.27
Scalp between- 1.20 patient (endpoint) Scalp within-pa- 1.33 tient (endpoint) Scalp between- NA patient (% change)
2.11
NA
1.34
2.75
NA
NA
NA
NA
NA
NA
NA
NA
NA
0.25
0.33
NA: not available; H2H: head-to-head Table 4. Overview of trials of scalp psoriasis
Analysis no
Group no
Effectiveness data
Sensitivity analy- Design sis within-patient (W); between-patient (B) yes B
Treatment duration
Effect size [CI]
Green 1994
4 wks
-1.09 [-1.69, -0. 48] -0.96 [-1.89, -0. 02] -1.16 [-1.50, -0. 82] -1.22 [-1.69, -0. 76] -1.42 [-1.80, -1. 04] -1.20 [-1.53, -0. 87] -1.08 [-1.45, -0. 71] -1.67 [-1.90, -1. 43]
495
Elie 1983
yes
3 wks
Franz 1999
yes
2 wks
11
Pauporte 2004
yes
3 wks
Ellis 1988
yes
3 wks
Franz 2000
yes
2 wks
Jarratt 2004
yes
4 wks
Olsen 1991
yes
2 wks
Table 4. Overview of trials of scalp psoriasis
(Continued)
Lepaw 1978
yes
2 wks
-1.11 [-1.69, -0. 53] -1.68 [-2.73, -0. 63] -0.07 [-0.82 0.68]
Elie 1983
no
3 wks
Shuttleworth 1998 Elie 1983
no
4 wks
19
no
3 wks
-0.96 [1.89, -0. 02] -0.48 [-1.15 0.18] 0.22 [-0.39 0.83] 0.39 [0.20 0.57] 0.37 [0.05 0.69] -0.49 [-0.68, -0. 29] -0.75 [-1.19, -0. 32]
6 7 7 8 15
22 2 2 1 1
Kanzler 1993 Duweb 2000 Klaber 1994 Reygagne 2002b Klaber 2000b
no yes yes no no
W B B B B
4 wks 6 wks 4 wks 4 wks 8 wks
15
van de Kerkhof 2002a 16
no
4 wks
Total number studies
Table 5. Overview of analyses: evidence of effectiveness outcomes
Analysis no 01 02 03 04 05 06 07 08
No studies 24 17 11 3 1 20 15 2
scalp trials 1 3 5 0 0 3 2 1
nail trials 0 0 0 0 0 1 0 0
inverse psoriasis 0 0 0 0 0 1 0 0
% Between-patient 54% 88% 73% 33% 100% 50% 73% 100%
No. participants 4509 2386 1571 47 318 741 3900 191

496
Table 5. Overview of analyses: evidence of effectiveness outcomes
(Continued)
09 10 11 12 13 14 15 16 17 18
2 7 2 4 12 2 3 2 1 6
0 0 0 0 0 0 2 0 0 0
0 0 0 0 0 0 0 0 0 0
0 0 0 1 0 0 0 0 0 0
100% 86% 50% 50% 83% 100% 100% 50% 0% 83%
1698 1198 57 342 5041 360 626 474 19 1349
Table 6. Analysis 01: Trial characteristics and outcomes: vit D / placebo
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 Combined endpoint
01 Calcipotriol Effect size [CI], -1.04 [-1.27, -0. -1.13, [-1.43, -0. -0.66, [-0.76, -0. -0.72, [-1.01, -0. -1.02, [-1.21, -0. OD/BD N, I 82], 9, 67.8% 83], 10, 81.5% 56], 7, 4.1% 42], 3, 35.7% 83], 15, 76.3% 02 Calcitriol Effect size [CI], -1.25 [-2.63, 0. -2.06, [-5.94, 1. OD/BD N, I 12], 4, 96.1% 82], 2, 98.3% 03 OD Tacalcitol Effect size [CI], -1.13 [-1.42, -0. -0.66, [-0.95, -0. N, I 83]1, NA 37]3, 47.7% -1.03, [-2.25, 0. 19], 5, 95.4% -0.82, [-1.34, -0. 29], 3, 82.7% -1.43, [-1.69, -1. 18], 2, 63.9% -1.90, [-2.09, -1. 71], 2, 21.5% -1.43, [-1.91, -0. 96], 1, NA -1.66, [-2.66, -0. 67], 1, NA
04 Dovobet, OD Effect size [CI], -1.58 [-1.82, -1. -1.31, [-1.51, -1. -1.38, [-2.02, -0. N, I 33], 1, NA 12], 1, NA 73], 2, 94.5% 05 Dovobet, BD Effect size [CI], -1.90 [-2.09, -1. N, I 71], 2, 21.5% 06 Maxacalcitol Effect size [CI], -1.43 [-1.91, -0. -1.61, [-2.10, -1. OD N, I 96], 1, NA 12], 1, NA 07 Paricalcitol Effect size [CI], -1.66 [-2.66, -0. -2.15, [-3.24, -1. OD N, I 67], 1, NA 06], 1, NA All treatments -1.41, [-1.86, -0. 97], 2, 86.9%
Effect size [CI], -1.30 [-1.57, -1. -1.28 [-1.60, -0. -0.91 [-1.18, -0. -0.72 [-1.01, -0. -1.17 [-1.38, -0. N, I 03], 15, 90.4% 95], 16, 92.3% 64], 7, 92.1% 42], 3, 35.7% 96], 24, 90.6%
497
Table 6. Analysis 01: Trial characteristics and outcomes: vit D / placebo
(Continued)
No. Participants Between-patient design Within-patient design
2556 8
2413 7
3203 6
488 3
4509 13
11
Treatment dura- 4 wks to 12 wks tion No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis Sensitivity analy- Within-patient ses trials Between-patient trials Scalp trials only 7 3 1 0 0
4 wks to 12 wks
3 wks to 8 wks
4 wks to 8 wks
3 wks to 12 wks
6 2 1 0 0
3 2 0 0 0
1 0 1 0 0
7 4 1 0 0 -1.19 [-1.70, -0. 69], 11, 91.4%. -1.16 [-1.39, -0. 92], 13, 90.6% -1.09 [-1.69, -0. 48], 1, NA -1.17 [-1.39, -0. 95], 23, 91.0% -0.56 [ -0.96, -0. 16], 4, 0% -1.06 [ -1.26, -0. 86], 12, 63.7% -0.89 [ -1.37, -0. 40], 3, 88.9%
All non-scalp trials Calcitriol, Perez 1996 removed Calcipotriol BD
Calcipotriol OD
498
Table 7. Analysis 02: Trial characteristics and outcomes: potent steroids / placebo
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 endpoint
Combined
01 Betametha- Effect size [CI], sone dipro- N, I pionate, maintenance 02 Betametha- Effect size [CI], sone dipropi- N, I onate OD
-1.00 [-1.68, -0. 32], 1, NA
-1.00 [-1.68, -0.32], 1, NA
-0.83 [-1.00, -0. -1.09 [-1.28, -0. 66], 2, 0% 90], 1, NA
-0.83 [-1.00, -0.66], 2, 0%
03 Betametha- Effect size [CI], -1.34 [-1.54, -1. -0.73 [-1.28, -0. -1.21 [-1.44, -0. sone dipropi- N, I 14], 5, 0% 17], 2, 0% 97], 1, NA onate BD 04 Betametha- Effect size [CI], -1.41 [-1.93, -0. -1.15 [-1.47, -0. sone valerate N, I 90], 1, NA 83], 2, 0% 05 Budesonide Effect size [CI], N, I Effect size [CI], -0.87 [-1.40, -0. -1.14 [-1.69, -0. N, I 34], 1, NA 60], 1, NA -0.34 [-0.75, 0. 07], 1, NA
-1.34 [-1.54, -1.14], 5, 0%
-1.22 [-1.50, -0.95], 3, 0%
06 Desonide
-0.87 [-1.40, -0.34], 1, NA -0.34 [-0.75, 0.07], 1, NA -0.93 [-1.14, -0.72], 2, 0%
07 Diorasone Effect size [CI], diacetate N, I 08 Fluticasone Effect size [CI], -0.93 [-1.14, -0. propionate N, I 72], 2, 0% 09 Hydrocorti- Effect size [CI], sone buteprate N, I
-0.46 [-0.77, -0. 15], 1, NA
-0.46 [-0.77, -0.15], 1, NA -0.75 [-1.17, -0.34], 1, NA -1.22 [-1.69, -0.76], 1, NA
10 Mometasone Effect size [CI], -0.75 [-1.17, -0. -1.18 [-1.62, -0. furoate N, I 34], 1, NA 74], 1, NA 11 Fluocinolone Effect size [CI], -1.22 [-1.69, -0. -0.89 [-1.34, -0. acetonide, plus N, I 76], 1, NA 44], 1, NA occlusion All treatments Effect size [CI], -1.09 [-1.26, -0. -0.84 [-1.01, -0. -1.14 [-1.29, -0. NA N, I 92], 11, 34.9% 67], 11, 42.7% 99], 2, 0% No. Participants Between-patient design 1232 10 1536 10 1054 2
-0.95 [-1.11, -0.80], 17, 61.1% 2386 15
499
Table 7. Analysis 02: Trial characteristics and outcomes: potent steroids / placebo
(Continued)
Within-patient design
2 wks to 12 wks
4 wks to 4 wks
2 wks to 12 wks
9 1 3 0 0
2 1 0 0 0
10 4 3 0 0 -1.34 [-1.78, -0.89], 2, 0%. -0.92 [-1.09, -0.76], 15, 62.8% -1.16 [-1.43, -0.90], 3, 0%. -0.92 [-1.10, -0.74], 14, 65.5%.
All non-scalp trials Table 8. Analysis 03: Trial characteristics and outcomes: v. potent steroids / placebo
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
01 Amcinonide
Effect size [CI], -1.42 [-1.80, -1. -1.31 [-1.70, -0. N, I 04], 1, NA 92], 1, NA
-0.97 [-1.33, -0.61], -1.42 [-1.80, -1.04], 1, NA 1, NA -1.01 [-1.55, -0.47], -1.24 [-1.50, -0.98], 1, NA 6, 70.1% -1.11 [-1.69, -0.53], 1, NA -1.25 [-1.46, -1.04], -1.36 [-1.65, -1.07], 2, 0% 3, 47.1% -1.16 [-1.34, -0.99], -1.29 [-1.45, -1.13], 4, 0% 11, 53.2%
500
02 Clobetasol Effect size [CI], -1.32 [-2.07, -0. -1.23 [-1.39, -1. propionate N, I 57], 2, 85.1% 07], 5, 26.2% 03 Halcinonide Effect size [CI], -1.11 [-1.69, -0. N, I 53], 1, NA Effect size [CI], -1.81 [-2.37, -1. N, I 24], 1, NA Effect size [CI], -1.42 [-1.72, -1. -1.24 [-1.38, -1. NA N, I 11], 5, 59.6% 11], 6, 9.7%
04 Halobetasol
All treatments
Table 8. Analysis 03: Trial characteristics and outcomes: v. potent steroids / placebo
(Continued)
No. Participants Between-patient design Within-patient design
684 4
1188 6
415 2
1571 8
2 wks to 4 wks
2 wks to 3 wks
2 wks to 4 wks
2 0 4 0 0
3 0 1 0 0
4 0 5 0 0 -1.23 [-1.43, -1.04], 3, 0%. -1.31 [-1.53, -1.10], 8, 65.0% -1.33 [-1.59, -1.08], 5, 61.0% -1.24 [-1.43, -1.04], 6, 38.2%
All non-scalp trials Table 9. Analysis 04: Trial characteristics and outcomes: dithranol/ placebo
Subcategory 01 Dithranol
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI NA
05 Combined endpoint -1.05 [-1.65, -0.46], 3, 36.8%
Effect size [CI], -1.14 [-2.22, -0. -1.06 [-1.66, -0. NA N, I 06], 1, NA 46], 3, 37.4% No. Participants Between-patient design Within-patient design 8 0 47 0
All treatments
47 0
501
Table 9. Analysis 04: Trial characteristics and outcomes: dithranol/ placebo
(Continued)
Treatment dura- 3 wks to 3 wks tion No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis 1 0 0 0 0
3 wks to 8 wks
3 wks to 8 wks
1 0 0 0 0
1 0 0 0 0
Table 10. Analysis 06: Trial characteristics and outcomes: other treatments / placebo
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 Combined endpoint -1.62 [-2.21, -1. 03], 1, NA -0.59 [-1.01, -0. 16], 1, NA
01 Aloe vera ex- Effect size [CI], tract N, I 02 Anti Effect size [CI], -0.59 [-1.01, -0. -0.70 [-1.13, -0. IL-8 monoclonal N, I 16], 1, NA 27], 1, NA antibody cream 03 Betametha- Effect size [CI], -1.68 [-2.73, -0. -0.95 [-1.89, -0. sone-17,21N, I 63], 1, NA 01], 1, NA dipropionate plus salicylic acid 04 Betametha- Effect size [CI], -0.76 [-1.21, -0. sone 17-valerate N, I 31], 1, NA 21 acetate plus tretinoine plus salicylic acid 05 Ci- Effect size [CI], clopirox olamine N, I shampoo 06 Ciclosporin Effect size [CI], solution in oil N, I 07 Dead sea salts Effect size [CI], emollient lotion N, I -0.07 [-0.82, 0. 68], 1, NA
-1.62 [-2.21, -1. 03], 1, NA
-1.68 [-2.73, -0. 63], 1, NA
-0.54 [-0.99, -0. -0.80 [-1.26, -0. -0.76 [-1.21, -0. 10], 1, NA 35], 1, NA 31], 1, NA
-0.11 [-0.86, 0. -0.07 [-0.82, 0. 64], 1, NA 68], 1, NA
-1.24 [-2.33, -0. 14], 1, NA 0.57 [-0.36, 1. 51], 1, NA
-3.94 [-5.79, -2. -1.24 [-2.33, -0. 09], 1, NA 14], 1, NA 0.57 [-0.36, 1. 51], 1, NA
502
(Continued)
08 Fish oil plus Effect size [CI], occlusion N, I
-1.07 [-1.66, -0. 47], 1, NA
-1.07 [-1.66, -0. 47], 1, NA -0.62 [-1.35, 0. 12], 1, NA
09 Hexauoro- Effect size [CI], -0.62 [-1.35, 0. -1.13 [-1.91, -0. 1,25-dihydroxN, I 12], 1, NA 35], 1, NA yvitamin D3 10 Methotrexate Effect size [CI], -0.56 [-1.01, -0. -0.48 [-0.92,-0. -1.62 [-2.21, -1. gel N, I 12], 1, NA 04], 1, NA 03], 1, NA 11 Mycopheno- Effect size [CI], lic acid ointment N, I 12 NG- Effect size [CI], monomethyl-L- N, I arginine (LNMMA) cream -1.44 [-2.67, -0. 22], 1, NA 0.08 [-0.60, 0. 75], 1, NA
-1.07 [-2.11, -0. 04], 2, 87.2% -1.44 [-2.67, -0. 22], 1, NA 0.08 [-0.60, 0. 75], 1, NA
13 Oleum hor- Effect size [CI], -0.02 [-0.63, 0. -0.77 [-1.40, -0. wathiensis N, I 58], 1, NA 14], 1, NA 14 Omega-3- Effect size [CI], polyunsatN, I urated fatty acids ointment 15 Pimecrolimus Effect size [CI], -1.07 [-1.69, -0. -1.28 [-1.86, -0. cream, 1% BD N, I 45], 1, NA 71], 1, NA 16 Platelet aggre- Effect size [CI], -0.07 [-0.50, 0. gation activating N, I 37], 1, NA factor (PAF)(Ro 24-0238) 17 Polymyxin B Effect size [CI], cream, 200, N, I 000U/g 18 PTH Effect size [CI], (1-34) in Nova- N, I some A liposomal cream, BD 19 Salicylic acid 0.13 [-0.59, 0. 85], 1, NA
-0.02 [-0.63, 0. 58], 1, NA
-0.65 [-1.24, -0. -1.07 [-1.69, -0. 06], 1, NA 45], 1, NA -0.07 [-0.50, 0. 37], 1, NA
0.13 [-0.59, 0. 85], 1, NA
-2.31 [-3.26, -1. 36], 1, NA
-2.31 [-3.26, -1. 36], 1, NA
Effect size [CI], -0.96 [-1.89, -0. -0.59 [-1.49, 0. N, I 02], 1, NA 31], 1, NA -0.39 [-0.98, 0. 21], 1, NA
-0.96 [-1.89, -0. 02], 1, NA -0.39 [-0.98, 0. 21], 1, NA

503
20 Effect size [CI], Sirolimus (topi- N, I cal), 2.2% for 6
(Continued)
wks, then 8% for a further 6 wks 21 Tacrolimus Effect size [CI], ointment N, I 22 Tar 0.06 [-0.51, 0. 63], 1, NA 0.06 [-0.51, 0. 63], 1, NA -0.48 [-1.15, 0. 18], 1, NA 220 4 181 4 741 11
Effect size [CI], -0.48 [-1.15, 0. -0.45 [-1.11, 0. N, I 18], 1, NA 22], 1, NA No. Participants Between-patient design Within-patient design 401 5 503 7
All treatments
10
3 wks to 12 wks
3 wks to 12 wks
3 wks to 12 wks
3 wks to 12 wks
17 2 3 1 1
4 0 0 0 0
4 1 1 1 1
21 2 3 1 1
Table 11. Analysis 07: Trial characteristics and outcomes: vit D / potent steroids
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 Combined endpoint 0.19 [-0.17, 0. 55], 2, 92.1%
01 Cal- Effect size [CI], 0.00 [-0.16, 0. 0.37 [0.24, 0. 0.41 [0.30, 0. cipotriol vs. be- N, I 16], 1, NA 50], 1, NA 51], 2, 13.6% tamethasone dipropionate
02 Calcipotriol Effect size [CI], 0.19 [-0.13, 0. -0.06 [-0.34, 0. -0.12 [-0.22, -0. -0.04 [-0.46, 0. 0.02 [-0.22, 0. vs. betametha- N, I 52], 3, 78.0% 23], 3, 75.9% 02], 4, 0.0% 39], 3, 94.3% 25], 6, 83.1% sone valerate 03 Calcipotriol Effect size [CI], vs. desoxymeta- N, I sone 0.15 [-0.73, 1. 02], 1, NA 0.15 [-0.73, 1. 02], 1, NA
504
(Continued)
04 Effect size [CI], 0.27 [0.02, 0. 0.40 [0.15, 0. Calcipotriol vs. N, I 52], 1, NA 64], 1, NA diorasone diacetate 05 Calcipotriol Effect size [CI], -0.58 [-0.99, -0. -0.49 [-0.91, -0. vs. uocinonide N, I 18], 1, NA 06], 1, NA 06 Calcitriol vs. Effect size [CI], 0.21 [-0.04, 0. 0.26 [0.02, 0. 0.39 [0.14, 0. betamethasone N, I 45], 1, NA 51], 1, NA 63], 1, NA dipropionate 07 Calcitriol vs. Effect size [CI], -0.19 [-0.91, 0. betamethasone N, I 53], 1, NA valerate 08 Tacalcitol vs. Effect size [CI], betamethasone N, I valerate All treatments 0.41 [0.08, 0. 74], 2, 0.0%
0.27 [0.02, 0. 52], 1, NA
-0.58 [-0.99, -0. 18], 1, NA 0.21 [-0.04, 0. 45], 1, NA
-0.19 [-0.91, 0. 53], 1, NA
0.41 [0.08, 0. 74], 2, 0.0%
Effect size [CI], 0.07 [-0.11, 0. 0.14 [-0.08, 0. 0.12 [-0.09, 0. -0.04 [-0.46, 0. 0.08 [-0.07, 0. N, I 26], 8, 73.9% 37], 9, 85.7% 34], 8, 88.0% 39], 3, 94.3% 24], 15, 80.6% No. Participants Between-patient design Within-patient design 2057 7 2334 5 3033 6 1206 2 3900 10
Treatment dura- 3 wks to 8 wks tion No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis Sensitivity analy- Within-patient ses trials 6 1 2 0 0
3 wks to 6 wks
4 wks to 8 wks
4 wks to 6 wks
3 wks to 8 wks
6 0 2 0 0
4 1 0 0 0
1 0 1 0 0
8 1 2 0 0 0.17 [-0.20, 0. 53], 5, 81.7%.
505
(Continued)
Between-patient trials Scalp trials only
-0.06 [-0.11, 0. 23], 10, 79.0% 0.37 [0.20, 0. 55], 2, 0% 0.04 [-0.12, 0. 21], 13, 80.5%
All non-scalp trials Table 12. Analysis 09: Trial characteristics and outcomes: vit D + p. ster / p. ster
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 endpoint
Combined
01 Calcipotriol Effect size [CI], -0.46 [-0.60, -0. -0.43 [-0.56, -0. -0.48 [-0.58, -0. / betamethasone N, I 31], 1, NA 31], 1, NA 38], 2, 0.0% dipropionate combination ointment (Dovobet) vs. betamethasone dipropionate ointment Effect size [CI], -0.46 [-0.60, -0. -0.43 [-0.56, -0. -0.48 [-0.58, -0. NA N, I 31], 1, NA 31], 1, NA 38], 2, 0.0% No. Participants Between-patient design Within-patient design 732 1 966 1 1651 2
-0.44 [-0.54, -0.35], 2, 0.0%
-0.44 [-0.54, -0.35], 2, 0.0% 1698 2
Treatment dura- 4 wks tion No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis 1 0 0 0 0
4 wks
4 wks
4 wks
1 0 0 0 0
1 0 0 0 0
1 0 0 0 0
506
Table 13. Analysis 10: Trial characteristics and outcomes: vit D / dithranol Subcategory Measure 01 IAGI 02 TSS 03 PASI 04 PAGI 05 Combined endpoint
01 Calcipotriol Effect size [CI], -0.69 [-0.86, -0. -0.54 [-1.14, 0. 1.02 [-1.71, 3. -0.47 [-0.65, -0. -0.01 [-0.71, 0. vs. dithranol N, I 51], 3, 36.6% 07], 2, 70.3% 76], 2, 98.6% 28], 1, NA 69], 5, 95.8% 02 Tacalcitol vs. Effect size [CI], dithranol N, I -0.18 [-0.60, 0. -0.07 [-0.50, 0. 25], 1, NA 36], 1, NA -0.18 [-0.60, 0. 25], 1, NA 0.51 [0.14, 0. 88], 1, NA
03 Calcitriol vs. Effect size [CI], 0.51 [0.14, 0. 0.13 [-0.24, 0. -0.19 [-0.56, 0. dithranol N, I 88], 1, NA 50], 1, NA 18], 1, NA All treatments
Effect size [CI], -0.40 [-0.87, 0. -0.27 [-0.73, 0. 0.41 [-0.47, 1. -0.47 [-0.65, -0. 0.04 [-0.53, 0. N, I 07], 4, 92.1% 19], 4, 80.1% 29], 4, 95.7% 28], 1, NA 61], 7, 95.2% No. Participants Between-patient design Within-patient design 1022 4 386 3 690 4 458 1 1198 6
4 wks to 8 wks
8 wks to 10 wks
8 wks
4 wks to 12 wks
3 0 0 0 0
3 0 0 0 0
1 0 0 0 0
3 0 0 0 0
Table 14. Analysis 11: Trial characteristics and outcomes: vit D / coal tar
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 Combined endpoint -1.01 [-1.77, -0. 24], 1, NA
01 calcipotriol Effect size [CI], -1.01 [-1.77, -0. vs. coal tar N, I 24], 1, NA 02 vs. Effect size [CI], -1.21 [-1.79, -0. calcipotriol N, I 62], 1, NA white soft parafn + coal tar
-0.84 [-1.39, -0. -1.51 [-2.12, -0. -1.21 [-1.79, -0. 28], 1, NA 90], 1, NA 62], 1, NA
507
Table 14. Analysis 11: Trial characteristics and outcomes: vit D / coal tar
(Continued)
All treatments
Effect size [CI], -1.13 [-1.60, -0. NA N, I 67], 2, 0.0% No. Participants Between-patient design Within-patient design 57 1
-0.84 [-1.39, -0. -1.51 [-2.12, -0. -1.13 [-1.60, -0. 28], 1, NA 90], 1, NA 67], 2, 0.0% 27 0 27 0 57 1
6 wks
6 wks
6 wks to 6 wks
1 0 0 0 0
1 0 0 0 0
2 0 0 0 0
Table 15. Analysis 12: Trial characteristics and outcomes: vit D / vit D
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 endpoint
Combined
01 Calcipotriol Effect size [CI], vs. calcitriol N, I
0.61 [0.28, 0. -1.11 [-2.22, 0. 93], 1, NA 01], 1, NA
-0.16 [-1.83, 1.51], 2, 88.0% -0.47 [-0.73, -0.21], 1, NA 0.43 [-0.12, 0.98], 1, NA -0.05 [-0.76, 0.67], 4, 90.4% 342 2
02 Calcipotriol Effect size [CI], -0.47 [-0.73, -0. -0.45 [-0.68, -0. vs. tacalcitol N, I 21], 1, NA 22], 1, NA 03 Calcipotriol Effect size [CI], 0.43 [-0.12, 0. 0.13 [-0.41, 0. vs. maxacalcitol N, I 98], 1, NA 68], 1, NA All treatments Effect size [CI], -0.06 [-0.93, 0. 0.09 [-0.65, 0. -1.11 [-2.22, 0. NA N, I 82], 2, 87.9% 82], 3, 92.6% 01], 1, NA No. Participants Between-patient design 252 1 388 1 15 1
508
Table 15. Analysis 12: Trial characteristics and outcomes: vit D / vit D
(Continued)
Within-patient design
6 wks to 8 wks
8 wks
6 wks to 8 wks
3 0 0 1 0
1 0 0 0 0
3 0 0 1 0
Table 16. Analysis 13: Trial characteristics and outcomes: vit D / vitD+ steroid
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 endpoint
Combined
01 calcipotriol Effect size [CI], 0.53 [0.22, 0. vs. N, I 84], 1, NA calcipotriol then cal. OM, BMV ON 02 cal- Effect size [CI], 0.60 [0.18, 1. 0.63 [0.21, 1. cipotriol vs. clo- N, I 02], 1, NA 05], 1, NA betasol propionate then calcipotriol 03 calcipotriol Effect size [CI], 0.56 [0.23, 0. vs. calcipotriol N, I 88], 1, NA OM, BMD ON 04 calcipotriol Effect size [CI], 0.26 [0.05, 0. vs. calcipotriol N, I 47], 1, NA OM, BMV ON 05 calcipotriol Effect size [CI], 0.00 [-0.21, 0. vs. N, I 21], 1, NA calcipotriol OM, clobetasone butyrate ON
0.70 [0.39, 1. 01], 1, NA
0.53 [0.22, 0.84], 1, NA
0.60 [0.18, 1.02], 1, NA
0.46 [0.14, 0. 78], 1, NA
0.56 [0.23, 0.88], 1, NA
0.19 [-0.02, 0. 40], 1, NA
0.26 [0.05, 0.47], 1, NA
0.17 [-0.04, 0. 38], 1, NA
0.00 [-0.21, 0.21], 1, NA
509
(Continued)
06 calcipotriol Effect size [CI], vs. N, I calcipotriol OM, diucortolone valerate ON 07 calcipotriol Effect size [CI], vs. N, I calcipotriol OM, uocinonide acetonide ON 08 calcipotriol Effect size [CI], 0.66 [0.40, 0. vs. Dovobet BD N, I 93], 3, 86.9% 09 calcipotriol Effect size [CI], 0.27 [0.06, 0. vs. Dovobet ON N, I 48], 1, NA (placebo OM) 10 calcipotriol Effect size [CI], vs. Dovobet OD N, I 11 Tacalcitol vs. Effect size [CI], Dovobet ON (4 N, I wks) then calcipotriol ON (4 wks) All treatments
0.08 [-0.29, 0. 44], 1, NA
0.08 [-0.29, 0.44], 1, NA
0.53 [-0.11, 1. 18], 1, NA
0.53 [-0.11, 1.18], 1, NA
0.64 [0.46, 0. 83], 3, 73.6% 0.40 [0.19, 0. 61], 1, NA
0.66 [0.40, 0.93], 3, 86. 9% 0.27 [0.06, 0.48], 1, NA
0.82 [0.69, 0. 0.69 [0.34, 1. 95], 1, NA 05], 2, 91.8% 0.78 [0.58, 0. 98], 1, NA
0.67 [0.36, 0.97], 2, 88. 8% 0.78 [0.58, 0.98], 1, NA
Effect size [CI], 0.46 [0.27, 0. 0.80 [0.68, 0. 0.52 [0.38, 0. NA N, I 66], 7, 86.3% 93], 2, 0.0% 66], 11, 83.3% No. Participants Between-patient design Within-patient design 2831 6 1018 1 4942 10
0.50 [0.35, 0.65], 12, 85.5% 5041 10
Treatment dura- 4 wks to 8 wks tion No. Treatments Study quality: A Scalp psoriasis 7 2 0
4 wks to 6 wks
2 wks to 8 wks
2 wks to 8 wks
2 0 0
10 3 0
11 3 0
510
(Continued)
Nail psoriasis Inverse psoriasis Sensitivity analy- Within-patient ses trials Between-patient trials Scalp trials only All non-scalp trials
0 0
0 0
0 0
0 0 0.33 [-0.18, 0.84], 2, 70.5% 0.52 [0.36, 0.68], 10, 86.7% NA NA
Table 17. Analysis 14: Trial characteristics and outcomes: vit D / p. ster+sal. acid
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
01 Cal- Effect size [CI], -0.06 [-0.33, 0. cipotriol vs. be- N, I 22], 1, NA tamethasone dipropionate + salicylic acid All treatments Effect size [CI], -0.06 [-0.33, 0. NA N, I 22], 1, NA No. Participants Between-patient design Within-patient design 200 1
-0.05 [-0.36, 0.26], -0.49 [-0.79, -0. -0.05 [-0.26, 0.15], 1, NA 20], 1, NA 2, 0.0%
-0.05 [-0.36, 0.26], -0.49 [-0.79, -0. -0.05 [-0.26, 0.15], 1, NA 20], 1, NA 2, 0.0% 160 1 186 1 360 2
Treatment dura- 6 wks tion No. Treatments Study quality: A Scalp psoriasis Nail psoriasis 1 0 0 0
6 wks
6 wks
6 wks to 6 wks
1 0 0 0
1 0 0 0
1 0 0 0
511
Table 17. Analysis 14: Trial characteristics and outcomes: vit D / p. ster+sal. acid
(Continued)
Inverse psoriasis
Table 18. Analysis 15: Trial characteristics and outcomes: vit D / tar polytherapy
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
01 Calcipotriol Effect size [CI], -0.49 [-0.68, -0. -0.28 [-0.48, -0. vs. coal tar,1%, N, I 29], 1, NA 09], 1, NA coconut oil, 1%, salicylic acid, 0. 5%, shampoo (Capasal ) 02 Calcipotriol Effect size [CI], -0.47 [-0.83, -0. -0.50 [-0.85, -0. vs. coal tar + al- N, I 11], 1, NA 15], 1, NA lantoin + hydrocortisone cream
-0.47 [-0.83, -0. 11], 1, NA
03 Calcipotriol Effect size [CI], -0.75 [-1.19, -0. -0.95 [-1.40, -0. -0.64 [-1.07, -0. -0.56 [-0.99, -0. -0.75 [-1.19, -0. vs. dithranol / tar N, I 32], 1, NA 51], 1, NA 21], 1, NA 13], 1, NA 32], 1, NA regimen All treatments Effect size [CI], -0.52 [-0.68, -0. -0.54 [-0.90, -0. -0.64 [-1.07, -0. -0.56 [-0.99, -0. -0.52 [-0.68, -0. N, I 36], 3, 0.0% 18], 3, 73.8% 21], 1, NA 13], 1, NA 36], 3, 0.0% No. Participants Between-patient design Within-patient design 626 3 639 3 87 1 87 1 626 3
4 wks to 8 wks
4 wks
4 wks
4 wks to 8 wks
3 0 2 0 0
1 0 1 0 0
1 0 1 0 0
3 0 2 0 0
512
Table 19. Analysis 16: Trial characteristics and outcomes: vit D OD / vit D BD Subcategory Measure 01 IAGI 02 TSS 03 PASI -0.10 [-0.34, 0.15], 1, NA 04 PAGI 05 Combined endpoint -0.10 [-0.34, 0.15], 1, NA
01 Cal- Effect size [CI], cipotriol BD vs. N, I calcipotriol OD 02 Cal- Effect size [CI], -0.27 [-0.48, -0. cipotriol BD vs. N, I 06], 1, NA calcipotriol OM, vehicle ON All treatments Effect size [CI], -0.27 [-0.48, -0. NA N, I 06], 1, NA No. Participants Between-patient design Within-patient design 344 1
-0.15 [-0.36, 0.06], 1, NA
-0.27 [-0.48, -0.06], 1, NA
-0.12 [-0.28, 0.03], NA 2, 0.0% 475 1
-0.19 [-0.37, -0.02], 2, 12.0%
474 1
8 wks to 8 wks
8 wks to 8 wks
2 0 0 0 0
2 0 0 0 0
Table 20. Analysis 17: Trial characteristics and outcomes: vit D / vit D + occlusion
Subcategory
Measure
01 IAGI
02 TSS 0.79 [0.13, 1.45], 1, NA
03 PASI
04 PAGI
05 Combined endpoint 0.79 [0.13, 1.45], 1, NA
01 Cal- Effect size [CI], cipotriol BD vs. N, I calcipotriol BD + occlusion ON All treatments Effect size [CI], NA N, I No. Participants
0.79 [0.13, 1.45], NA 1, NA 19
NA
0.79 [0.13, 1.45], 1, NA
19
513
Table 20. Analysis 17: Trial characteristics and outcomes: vit D / vit D + occlusion
(Continued)
Between-patient design Within-patient design Treatment duration No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis
8 wks
8 wks
1 0 0 0 0
1 0 0 0 0
Table 21. Analysis 18: Trial characteristics and outcomes: vit D / other treatment
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
01 Calcipotriol Effect size [CI], vs. propylth- N, I iouracil cream 02 Effect size [CI], Calcipotriol vs. N, I tacrolimus ointment 03 Calcipotriol Effect size [CI], vs. tazarotene N, I 04 Calcipotriol Effect size [CI], vs. tazarotene gel N, I plus mometasone furoate cream 05 Calcipotriol Effect size [CI], -0.55 [-1.33, 0. vs. vitamin B12 N, I 24], 1, NA cream -0.95 [-1.55, -0. 34], 1, NA
-2.24 [-3.23, -1. 25], 1, NA
-0.95 [-1.55, -0. 34], 1, NA
-0.05 [-0.33, 0. 23], 1, NA
-0.05 [-0.33, 0. 23], 1, NA
-0.01 [-0.78, 0. -0.55 [-1.33, 0. -0.55 [-1.33, 0. 75], 1, NA 24], 1, NA 24], 1, NA
514
Table 21. Analysis 18: Trial characteristics and outcomes: vit D / other treatment
(Continued)
06 Calcipotriol Effect size [CI], vs. Dovo- N, I bet (4 wks) then vitamin D3 (calcipotriol) weekdays/ (Dovobet) weekends (4 wks) 07 Effect size [CI], Tacalcitol vs. cal- N, I cipotriol (4 wks) then Dovobet (4 wks) No. Participants Between-patient design Within-patient design 13 0 246 2
0.23 [0.07, 0. 38], 1, NA
0.23 [0.07, 0. 38], 1, NA
0.78 [0.58, 0. 98], 1, NA
0.78 [0.58, 0. 98], 1, NA
1103 3
13 0
1349 5
6 wks to 12 wks
8 wks to 12 wks
12 wks
6 wks to 12 wks
2 0 0 0 0
4 1 0 0 0
1 0 0 0 0
6 1 0 0 0
Table 22. Analysis 05: Trial characteristics and outcomes: tazarotene / placebo
Subcategory 05 Tazarotene
Measure Effect size [CI], N, I No. Participants Between-patient design
01 IAGI
02 TSS
03 PASI
04 PAGI NA
05 Combined endpoint -0.91 [-1.16, -0.67], 1, NA
-0.91 [-1.16, -0. NA 67], 1, NA NA 318 1
All treatments
318 1
515
Table 22. Analysis 05: Trial characteristics and outcomes: tazarotene / placebo
(Continued)
Within-patient design Treatment duration No. Treatments Study quality: A Scalp psoriasis Nail psoriasis Inverse psoriasis
12 wks
12 wks
1 0 0 0 0
1 0 0 0 0
Table 23. Analysis 08: Trial characteristics and outcomes: vit D / v. potent steroids
Subcategory
Measure
01 IAGI
02 TSS
03 PASI
04 PAGI
05 Combined endpoint 0.08 [-0.60, 0.75], 2, 73.5%
01 Calcipotriol Effect size [CI], vs. Clobetasol N, I propionate All treatments Effect [CI]N, I size NA
0.37 [0.05, 0.69], -0.32 [-0.95, 0. 1, NA 30], 1, NA
0.37 [0.05, 0.69], -0.32 [-0.95, 0. NA 1, NA 30], 1, NA 151 1 40 1
0.08 [-0.60, 0.75], 2, 73.5%
No. Participants Between-patient design Within-patient design Treatment duration No. Treatments Study quality: A Scalp psoriasis Nail psoriasis
191 2
4 wks
6 wks
4 wks to 6 wks
1 0 1 0
1 1 0 0
1 1 1 0
516
Table 23. Analysis 08: Trial characteristics and outcomes: vit D / v. potent steroids
(Continued)
Inverse psoriasis Table 24. Included studies of adverse events Study Methods Participants
Intervention (s) Calcipotriol scalp solution 50 mcg/ml BD plus calcipotriol cream 50 mcg/ g BD (up to 70 g/wk) No control
Outcomes (AEs) Local AEs: Number of AEs/patient % Severe AEs Withdrawals due to adverse events (WA)
Summary ndings
Notes
Allocation conceal.
Barnes 2000
DESIGN: Within patient Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described
N: 202 TD: 52wks; FU: 52wks LF: 64 (32%) BC: NA Age: 46 (14. 5SD) Gender (%M) : 60% Severity: Scalp: TSS (0 to 12): 5.9; Overall assessment (investigator) : mild (31%); moderate (58%); severe (11%) Body: PASI (modied): 6. 8Overall assessment (investigator): mild (41. 5%); moderate (55%); severe (3.5%) INCLUSION CRITERIA Chronic plaque psoriasis on scalp and body; adult (18); outpatient EXCLUSION CRITERIA
Local AEs: Sponsored by D The most Leo Pharmacommon local ceuticals AE was facial irritation (60/ 202 patients at wk 2) though the Systemic AEs: incidence declined rapidly Serum over time (1/ calcium 141 at wk46) Serum PTH 20% of local Urinary calcium/ AEs considcreatinine ra- ered by investigator to be tio severe. 14% of patients withdrew because of adverse events Systemic AEs: No signicant changes observed
517
Table 24. Included studies of adverse events
(Continued)
Pregnancy or risk thereof; severe (i.e. requiring additional therapy) or unstable psoriasis; hypercalcaemia; history of hypo- or hyper-parathyroidism, renal/ hepatic disease; systemic or phototherapies within previous 6 wks; other medication that could affect course of disease Berth-Jones 1993; Berth Jones 1992c DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: NA STUDY A: N: 20 TD: 52 wks; FU: 52 wks LF: 0 (0%) BC: NA Age: 43 Gender (%M) : 65% Severity: mean PASI: 7.6 (3. 5SD) Study A: calcipotriol ointment 50 mcg/ g BD up to 100g/wk No control Local AEs: not assessed. Study A: no signicant trend in urine Systemic AEs: calcium excreurine calcium tion and phosphate Study B: excretion; serum signicant intotal calcium, crease in urine phosphate and calcium excre(relalkaline phos- tion ative to conphatase trols and to baseline) Sponsorship not reported For study B, baseline comparability of intervention and control groups not demonstrated. Berth Jones 1992 reports ndings for study A at 10 mths D
Study B: calcipotriol ointment 50 mcg/ g BD, using 100 g/wk for 4 wks STUDY B: Control: paN: in- tients using altervention: 10 ternative ther{32 controls} apies TD: 4 wks; FU: 4 wks LF: 0 (0%) BC: Not demonstrated Age: 48 {42} Gender (%M) : 50% {44%}
518
(Continued)
Severity: mean PASI: 18.0 (13.9SD) {NR} INCLUSION CRITERIA: Patients with chronic plaque psoriasis; aged 18; under long-term care of investigators. Study A: compliant patients, responsive to calcipotriol. Study B: more extensive disease, failing to respond to low doses of topical agents. Controls received no calcipotriol. EXCLUSION CRITERIA Pregnancy Bleiker 1998 DESIGN: Uncontrolled study Delivery: unclear ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Not described N: 28 TD: 2 wks; FU: 26 wks LF: unclear BC: NA Age: 47 (range: 18 to 83) Gender (%M) : 50% Severity: PASI: 21.4 (range: 8.2 to 53.7) INCLUSION CRISTUDY A: 200 g calcipotriol ointment 50 mcg/ g (wk 1) plus 300 g 50 mcg/ g calcipotriol (wk 2) Five patients Sponsorship developed hy- not reported percalSystemic AEs: caemia during Serum treatment, all total adjusted had received a dose > 5 g/kg calcium Nine patients Urinary became hypercalcium STUDY B: calciuric durCalcipotriol ing treatment; this was un50 mcg/ correlated g PRN <= 360 with dose g/wk Local AEs: Not assessed D
519
(Continued)
TERIA: Inpatients with severe chronic plaque psoriasis (> 15% BSA) EXCLUSION CRITERIA: Renal impairment, pregnancy, lactation, systemic treatment, diuretics Corbett 1976 DESIGN: Within patient Patient delivery ALLOCATION: random Method of randomisation: NR Concealment: unclear BLINDING: Doubleblind (patient/ investigator) WITHDRAWAL / DROPOUT: Not described N: 14 TD: 26 wks; FU: 26 wks LF: 2 (14.3%) BC (clinical): NR Age: 44 (18. 4SD) Gender (%M): 64% Severity: NR INCLUSION CRITERIA: Bilateral psoriasis involving <= 15% BSA; willing to participate for 6 months EXCLUSION CRITERIA: NR Clobetasol propionate 0.05% ointment, BD Betamethasone valerate 0.1% ointment, BD Local NR AEs: Quantities Sponsorship used by study not reported patients were Systemic AEs: small (mean: 7 Synacthen test g/wk) for function of No pituitarypituitaryadrenal axis at adrenal 0, 3 and 6 suppression months observed B
Gerritsen DESIGN: 2001; Uncontrolled Langner study 1996; van de Patient delivKerkhof ery ALLOCA1996c TION: NA Method of randomisation: NA Concealment: NA BLINDING: Open WITH-
N: 257 Calcitriol 3 Local AEs: TD: <= 78 mcg/g BD Sewks; FU: <= rious AEs re78 wks No control ported; WithLF: 4 (1.6%) drawals due to BC: NA adverse events Age: 42 (WA) (13SD) Gender (%M) Systemic AEs: : 61.3% Laboratory Severity: BSA: levels for: pro-
Local AEs: WA: 7/253; AEs: 37/353; No serious local adverse events. Systemic AEs: WA: 1/ 253. Four additional
Sponsored by D SolvayDuphar BV. Excludes scalp
520
(Continued)
DRAWAL / 14.0% (14. DROPOUT: 2%SD); PASI: Described 9.7; 47% had severe disease INCLUSION CRITERIA: Chronic plaque psoriasis; aged 18 EXCLUSION CRITERIA: noncompliant; pregnancy; use of systemic/ phototherapy within previous 2 mths; use of topical therapy within previous 1 wk; concomitant disease; clinically relevant abnormality in laboratory assessments; known hypersensitivity to vitamin D/vehicle Guzzo 1996 DESIGN: Between patient Patient delivery ALLOCATION: random Method of randomisation: NR Concealment: unclear BLINDING: Doubleblind (patient/ N: 78 TD: 8 wks; FU: 8 wks LF: 2 (2.6%) BC: No (one statistically signicant difference (% BSA higher in intervention group) Age: 48 Gender (%M) : 67% Severity: mean Calcipotriol 50 mcg/g ointment BD, up to 120 g/ wk Placebo
tein albumin; calcium, phosphorus, sodium, potassium, plasma calcitriol Urinary calcium, creatinine, phosphorus; creatinine clearance; urinary calcium / creatinine ratio
patients experienced hypercalcaemia. All mean values for all parameters remained within normal levels. Mean use: 6 g/ day (range: 1 to 24 g/day)
Local AEs: No adverse ef- Sponsored by B Not assessed fects on bone Bristol Myers metabolism or Squibb Systemic AEs: calcium Blood and urine chemistry analysis: parathyroid hormone, serum calcium, bone-specic alkaline phosphatase, urinary hyrox521
(Continued)
investigator) WITHDRAWAL / DROPOUT: Described
BSA: 9% INCLUSION CRITERIA: aged 18; stable plaque psoriasis; BSA: 5% to 20%. EXCLUSION CRITERIA: hypercalcaemia, bone, thyroid or parathyroid disease; topical therapy within previous 2 wks; systemic/ phototherapy within previous 8 wks N: 28 TD: 6 mths to 12 ys; FU: 6mths to 12 years LF: NA BC: demographic: yes; clinical: not demonstrated Age: 49 (13SD) Gender (%M) : 82% Severity: NR INCLUSION CRITERIA: psoriasis (any severity; types include plaque (16), generalized, seborrhoeic, guttate, erythrodermic) ; previous proPrevious prolonged treatment with topical uorinated steroids
yproline, 24hr urinary calcium excretion. Bone densitometry
Heng 1990
DESIGN: Between patient (retrospective study) Patient delivery ALLOCATION: nonrandom Method of randomisation: NA Concealment: NA BLINDING: NA WITHDRAWAL / DROPOUT: NA
Local AEs: light /electron microscopy for examination of basal keratinocyte herControl: steroid- nation (BKH) ; layers of basenegative group - previ- ment ous tar/UVB/ membrane. sunlight or no Systemic AEs: treatment NR
Local AEs: Light microscopy revealed no between group differences. Electron microscopy revealed multilayered, fragmented and disorganised basal laminae in the steroid group, which appeared to be correlated with duration of treatment. Fragmentation was not observed in the control group
Sponsorship not reported Nonpsoriatic control group also considered 16/28 patients had plaque psoriasis
522
(Continued)
longed treatment with topical uorinated steroids (range: 6 mths to 12 years). Control group matched for age and gender. EXCLUSION CRITERIA: NR Katz 1987b DESIGN Between patient Patient delivery ALLOCATION: random Method of randomisation: NS Concealment: unclear BLINDING: doubleblind (patient/ investigator) WITHDRAWAL / DROPOUT: Described N: 40 TD: 3 wks; FU: 3 wks LF: NA BC: demographic: yes; clinical: yes (gender imbalance) Age: 44 (range: 18 to 66) Gender (%M) : 53% Severity: 55% moderate disease; 45% severe disease INCLUSION CRITERIA: Aged 18; stable or worsening, moderate or severe chronic plaque psoriasis; baseline laboratory values within normal range (5 to 25 mcg%) EXCLUSION CRITERIA: Betamethasone dipropionate (0.05%) in optimised vehicle BD; Clobetasol 17 propionate (0.05%) ointment BD Local AEs: not assessedSystemic AEs: morning plasma cortisol levels; 24 hr urine steroid levels; FBC, blood chemistry, urinalysis Temporary reversible suppression of the hypothalamic-pituitaryadrenal axis in 8/40 patients Sponsorship B not reported; one author from Schering Corporation
523
(Continued)
Pregnancy or risk thereof; lactation; hypersensitivity to study medications; concurrent medication that could affect study outcomes; use ot systemic therapies within previous 4 wks; use of topical therapies within previous 2 wks Katz 1989 DESIGN: Within patient Patient delivery ALLOCATION: random Method of randomisation: unclear Concealment: unclear BLINDING: Doubleblind (patient/ investigator) WITHDRAWAL / DROPOUT: Described N: 30 TD: 2 wks; FU: 4 wks LF: 0 (0%) BC: yes Age: 55 (range: 36 to 69) Gender (%M) : 53% Severity: NR INCLUSION CRITERIA: bilateral symmetric chronic plaque psoriasis. EXCLUSION CRITERIA: Pregnancy or risk thereof; patients with overt signs of atrophy Betamethasone dipropionate (0.05%) in optimised vehicle BD (BMD) Clobetasol propionate (0.05%) ointment BD (CP) Uninvolved (nonpsoriatic) area used as test area for each patient Local AEs: skin surface microscopic examination with photographic documentation; oil and magnifying (8 x) lens to detect preatrophy (visibility of subpapillary vascular plexus caused by thinning of epidermis and papillary dermis). Local AEs: Sponsored by B No serious ad- Schering Corverse events poration observed with either treatment. Preatrophy identied in 20% of involved plaques (BMD: 11/ 59; CP: 12/ 59) and was more likely in females. In the test area (nonpsoriatic skin) , 5% of plaques showed preatrophy (BMD: 2/30; CP: 1/ Systemic AEs: 30). Preatrophy appeared NR to be usually reversible following treatment cessation
524
(Continued)
Kragballe 1991b
DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described
N: 15 TD: 26 wks; FU: 26 wks LF: 1(6.7%) BC: NA Age: 42 (range: 21 to 71) Gender (%M) : 53% Severity: %BSA: 14% (range: 5% to 30%) Most moderate severity INCLUSION CRITERIA: patients previously responding to calcipotriol during 8 wk clinical trial, but who had since relapsed. EXCLUSION CRITERIA: hypercalcaemia, impaired renal/ hepatic function, daily receiving > 400 i.u. vitamin D N: 157 TD: 26 wks; FU: 26 wks LF: 8 (5.1%) BC: NA Age: 44.4 (14. 0SD) Gender (%M) : 57% Severity: mean BSA: 13%; mean PASI: 9.
Calcipotriol ointment 50 mcg/ g BD (max: 100 g/wk). No control
Local AEs: Patient report of adverse events Investigator report of adverse events (skin examination). Skin biopsies to determine histologic signs of epidermal and dermal atrophy.
Face and scalp treated with emollient Systemic AEs: or hydrocortiNo consistent sone cream changes in lab- 1% (not caloratory analy- cipotriol) ses, with no clinically imSystemic AEs: portant Labchanges in oratory tests: serum calcium FBC, serum alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, total calcium, total phosphate
Local AEs: AE(L): 3/15 (reported to be transient & mild). Cases of mild to moderate atrophy found in 4/8 patients
Sponsorship D not reported. Leo Pharmaceuticals supplied study medication
Lambert 2002 DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING:
Tacalcitol ointment, 4 mcg/g OD. No control
Local AEs: Subjects asked about adverse events. Tolerability assessed by investigator (4 pt: 1 excellent to 4 poor) . Systemic AEs: Routine
Local AEs: WA: 5/157 (3. 4%) (treatmentrelated). AE(L): 26/157 (transient skin irritation) Tolerability at least moderate in 95% of pa-
Sponsored by D Hermal/BHI, Germany Scalp excluded Similar study to van de Kerkhof 2002, but unclear whether
525
(Continued)
Open WITHDRAWAL / DROPOUT: Described
4 (5.4SD). INCLUSION CRITERIA: chronic plaque psoriasis; aged 18 to 70; BSA 7% to 20%; laboratory parameters normal at baseline. EXCLUSION CRITERIA: pregnancy or risk thereof; topical antipsoriatic therapy within previous 2 wks; systemic antipsoriatic therapy within previous 6 wks; retinoids within previous 52 wks. ; history of hyperparathyroidism; concomitant use of drugs affecting calcium metabolism N: 40 TD: 26 wks; FU: 26 wks LF: 4 (10%) BC: No (Group A had less severe disease at baseline) Age: NR Gender (%M) : NR Initial regimen: all patients received 2 wks of calcipotriol (OM), halobetasol ointment (ON).
haematology and biochemistry: FBC, haemoglobin, bilirubin, creatinine, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyltranspeptidase, calcium, phosphate, sodium, potassium, glucose, urea, albumin. Urinalysis: calcium, creatinine, phosphate
tients.
Lambert 2002 is a report of a Systemic AEs: subgroup or a No serious ad- distinct study verse events and no hypercalcaemia.
Lebwohl 1998b
DESIGN: Between patient Patient delivery ALLOCATION: random. Method of randomisation: unclear Concealment: unclear
Local AEs: AE(L) (treatmentrelated; all irritant contact Systemic AEs: dermatitis): Group A: not assessed. 4/17 Group B: 1/20 No cutaneous atrophy Group A: Calobserved cipotriol oint-
Local AEs: Treatmentrelated adverse events
Sponsored B by Westwood Squibb Pharmaceuticals
526
(Continued)
BLINDING: Doubleblind (patient/ investigator) WITHDRAWAL / DROPOUT: Described
Severity: mild to moderate psoriasis INCLUSION CRITERIA: patients with at least moderate improvement in response to initial 2wk therapy regimen; aged 18; stable disease; BSA <= 20% (excluding face/ scalp); plaque elevation at least moderate; willing to comply with study protocol. EXCLUSION CRITERIA: history of sensitivity to study ingredients; topical antipsoriatics within previous 2 wks; UVB/ PUVA within previous 8 wks; history of hypercalcaemia, recurrent illness N: 50 TD: 26 wks; FU: 26 wks LF: NR BC: NR Age: 55 Gender (%M)
ment 50 mcg/ g (weekdays) plus halobetasol 0.05% ointment BD (weekends) Group B: Placebo ointment (weekdays) plus halobetasol 0.05% ointment BD (weekends)
Lebwohl 2001 DESIGN: Between patient Patient delivery ALLOCATION: random Method
Open label phase: tazarotene 0. 1% gel plus clobetasol propionate 0.05%
Local AEs: No. steroidspecic side effects Withdrawals due to adverse events
Local AEs: No steroidspecic side effects WA: 0/50 AE(L) (treatment-related):
Sponsorship: not reported No adequate effectiveness data reported. Numbers sub-
527
(Continued)
of randomisation: NR Concealment: unclear BLINDING: Doubleblind (patient / investigator) WITHDRAWAL / DROPOUT: Not described
: NR Severity: NR INCLUSION CRITERIA Moderate to severe plaque psoriasis; BSA <=15%. All patients participated in an open label treatment phase for 6 wks (tazarotene gel 0.1% OM, clobetasol propionate ointment 0. 05% ON) EXCLUSION CRITERIA Topical antipsoriatic treatment within previous 2 wks; UV treatment within previous 4 wks; systemic antipsoriatic treatment within previous 8 wks N: 160 TD: 54 wks; FU: 54 wks LF: 6 (3.8%) BC: NA Age: 48.2 (16. 1SD) Gender (%M) : 82% Severity: mean PASI: 22.49 (10. 2SD) IN-
ointment for 6 wks. Once daily initially, then tapered. Maintenance phase (20 wks) : Tazarotene gel, 0. 1%, OM (3/7 days) , plus clobetasol propionate 0.05% ointment ON (2/ 7days) (TC) Tazarotene gel, 0. 1%, OM (3/7 days), placebo ointment OM (2/7 days) , placebo ointment ON (2/7 days) (TP) Placebo gel OM (3/7 days), placebo ointment ON (2/7 days) (P)
(WA) Drug- TC: 24% TP: jects in each related adverse 29% P: 0% group NR events Systemic AEs: not assessed
Miyachi 2002
DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING:
Tacalcitol ointment 20 mcg/g OD (max: 10 g/ day) No control
Local AEs: Treatmentrelated adverse events Systemic events: haematological tests (FBC) , blood biochemical tests (calcium, inorganic phos-
Local AEs: AE(L): 16/ 154 (29 events, all mild to moderate) Systemic AEs:
Sponsorship: not reported Scalp treated in 74/154 subjects
Usual dosing regimen AE(S): 85/154 for tacalcitol is (155 events, of 4 mcg/g OD which 6 were considered
528
(Continued)
Open WITHDRAWAL / DROPOUT: Described
CLUSION CRITERIA: inpatients and outpatients with BSA 10%. EXCLUSION CRITERIA: pregnancy; lactation severe liver disease, heart disease, impaired renal function, hypercalcaemia; treatment with topical, UV or systemic antipsoriatics within previous 2 wks
phorus, albumin, protein, bilirubin, urea nitrogen, creatinine, GP/ AST, GPT/ ALT, alkaline phosphatase, LDH, intact PTH), urinalysis (glucose, protein) ; serum tacalcitol and vitamin D3 levels.
treatment-related). Serum levels of intact PTH and tacalcitol decreased, suggesting percutaneous absorption of tacalcitol. However, mean levels of serum calcium remained within the standard level. Data on individual responses not reported. High dose tacalcitol affected serum calcium in patients with reduced renal function Sponsored by D Leo Pharmaceuticals Face/scalp excluded
Poyner 1993
DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: open WITHDRAWAL / DROPOUT: Described
N: 203 TD: 48 wks; FU: 48 wks LF: 59 (29. 1%) BC: NA Age: 43. 8 (range: 17 to 80) Gender (%M) : 52.7% Severity (assessment methods NR) : mild (8%) ; moderate (63%); severe (30%). INCLUSION CRITERIA: aged 18;
Calcipotriol Loca AEs: 50 mcg/g Self report of adverse ointment events. Withdrawals No control due to adverse events (WA)
Local AEs: WA: 8/203 AE(L): 83/ 203 142 events reported by 83 (41%) patients with 20. Systemic AEs: 2% being lesional / biochemical and haemato- perilesional irritation. logical tests Compliance: self-reported usage at each visit; weighing of ointment tubes Systemic AEs: No signicant changes in haematological values. Mean serum calcium
529
(Continued)
chronic plaque psoriasis 100 cm2 . EXCLUSION CRITERIA: PUVA within previous 8 wks; elevated serum calcium, unstable disease, impaired hepatic/renal function pregnancy; concomitant oral calcium /vitamin D. topical antipsoriatics, lithium, systemic steroids Ramsay 1994 DESIGN: Uncontrolled open study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described N: 167 TD: 52 wks; FU: 52 wks LF: 39 (23.4%) BC: NA Age: 49 (range: 20 to 85) Gender (%M): 60% Severity: PASI (modied): 8.1 (6.7SD) INCLUSION CRITERIA: chronic plaque psoriasis; previous response to calcipotriol; managed by specialists. EXCLUSION CRITERIA: pregnancy or risk thereof; Calcipotriol 50 mcg/g ointment. Max dose: 100 g/wk; 2,500g/ pa Face/scalp/ neck excluded No control Local AEs: self report of adverse events: mild, moderate, severe; unlikely, possibly or probably treatmentrelated. Systemic AEs: haematology (erythrocyte, haemoglobin, leukocyte, platelet counts) and biochemistry (bilirubin, AST/ALT, alkaline phosphatase, albumin, urate, creatinine,
did not change signicantly over study period. Signicant fall in serum urate in those treated 36 wks. Compliance: median weekly use (wks 0 to 5): 16.5g; (wks 43 to 48): 11.6g
AE(L): Sponsored by D 52/161 60 (46 Leo Pharmaconsidered to ceuticals be treatmentrelated) events reported by 52 of 161 subjects. One subject developed a signicant rise in serum calcium. No other abnormalities in haematology or biochemistry tests. 118/161 subjects reported continuous medication use and 80% to 90%
530
(Continued)
abnormal serum calcium or phosphate; impaired hepatic/renal function; concomitant oral calcium/ vitamin D; systemic therapy within previous 8 wks; topical therapy within previous 4 wks van de Kerkhof 1997b DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: open WITHDRAWAL / DROPOUT: Described N: 58 TD: <= 60 wks; FU: <= 60 wks LF: 16 (27. 6%) BC: NA Age: 45 (range: 19 to 78) Gender (%M) : 69.0% Severity: BSA: 8.6% (3.9SD) ; TSS (0 to 12) :7.9 (2.1SD). INCLUSION CRITERIA: patients with chronic plaque psoriasis participating in previous double blind study (Van de Kerkhof 1996b); aged 25 to 80; normal serum calcium / Part 1: doubleblind study (8wks): Tacalcitol 4 mcg/g ointment OD Placebo Part 2: open follow up study (4 wk washout period): Tacalcitol 4 mcg/g ointment OD, <= 20 mg/day and < 2000 g per patient over study period. Patients could discontinue treatment after 12 wks. No control
phosphate, total calcium) tests Compliance: self report of number tubes used and number daily doses
used it twice daily. Mean use: 35. 1g/wk (initially) to 23. 4 g/wk during last 6 mths
Local AEs: occurrence of adverse events (duration, severity and whether treatment-related) Patient and investigator assessments of tolerability (4 pt: v. good (3) to insufcient (0))
Local AEs: WA: 0/58 AE (L): 10/58 (19 events) AE(L) (treatmentrelated): 8/58 Tolerability: Investigator assessment: 2.60 (0. 53SD, N = 58) ; patient assessment: 2.53 (0. Systemic AEs: 63SD, N = 58) haematology . (erythrocytes, platelets, hae- Systemic AEs: moglobin, AE(S): 0/58 haematocrit) No case of hy; blood chem- percalcaemia. istry (serum calcium, inorganic phosphate, creatinine, ASAT, alkaline phosphatase, LDH)
Sponsorship not reported Follow-up study to Van de Kerkhof 1996b - 3 of 15 centres participated Scalp excluded
531
(Continued)
phosphate. EXCLUSION CRITERIA: pregnancy or risk thereof; topical therapy within previous 4 wks; systemic therapy within previous 8 wks; serious disease; known allergy to study medication; concomitant medication that could interfere with study drug or systemic calcium metabolism van de Kerkhof 2002c (see also Lambert 2002) DESIGN: Uncontrolled study Patient delivery ALLOCATION: nonrandom Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described Part 1: N: 304 TD: 13 wks; FU: 13 wks LF: 47 (15. 5%) BC: NA Age: 44 (range: 15 to 76) Gender (%M) : 57% Severity: median PASI (modied to exclude head): 9.5 (range: 2.2 to 24.4); TSS (0 to 12): 6.0 Part 2: N: 197 TD: 65 wks; FU: 65 wks Tacalcitol 4 mcg/ g OD. Treatment discontinued during remission and restarted if relapse No control Local AEs: number treatmentrelated adverse events; withdrawals due to adverse events (WA); investigator assessment of tolerability; patient assessment of tolerability. Systemic AEs: Haematology: serum calcium, parathyroid hormone (PTH), calcitonin, calLocal AEs: WA: 18 /304 AE(L): 65/ 304 Tolerability excellent/good in 76% (patient assessment) to 92% (investigator assessment) of patients at nal assessment. Systemic AEs: No clinically significant changes in routine haematology, urinalysis Sponsored by D Hermal/BHI, Germany Scalp excluded
532
(Continued)
LF: 83 (42. 1%) BC: NA Age: NR Gender (%M) : NR Severity: NR INCLUSION CRITERIA: chronic plaque psoriasis; BSA 7% to 20% (excluding scalp); aged 18 to 70; normal baseline laboratory values. Part 2 of study: responders to part 1 ( 30% reduction in sum score (TSS) from baseline). EXCLUSION CRITERIA: topical steroids in previous 2 wks; systemic antipsoriatics within previous 6 wks; retinoids within previous 52 wks; known hypersensitivity to vitamin D3 analogues; serious concomitant disease; disease that might
citriol Urine: calcium, creatinine, calcium/ creatinine ratio. Compliance with medication
or serum chemistry. Compliance with treatment regimen varied between 82% and 92%. However, 54% of those with BSA 10% to 20% exceeded recommended daily dose of 5 g (up to 13 g daily), but there was no effect on calcium homeostasis. Duration of excess dosing not reported
533
(Continued)
interfere with study assessments; concomitant use of oral calcium/ vitamin D; pregnancy or risk thereof VazquezLopez 2004 DESIGN: Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described N: 20 TD: 26 wks; FU: 34 wks LF: 0 (0%) BC: NA Age: 28. 2 (range: 20 to 55) Gender (%M) : 40% Severity: NR INCLUSION CRITERIA: absence of visible or dermascopic red lines (linear telangiectasias). EXCLUSION CRITERIA: use of topical steroids in previous 2 mths Clobetasol propionate 0.05% cream, OD (weekends) plus calcipotriol 50 mcg/g ointment BD (weekdays) No control Local AEs: Clinical (naked eye) examination of psoriatic plaque and surrounding area Dermoscopic examination of psoriatic plaque and surrounding area Systemic AEs: NR Compliance: quantity and frequency of study drug use (tubes weighed) Overuse of topical steroids resulted in appearance of clinically unapparent but dermoscopically apparent linear telangiectasias. 7/20 patients failed to adhere to recommended steroid dosing schedules. Dermoscopic red lines not apparent in 15/20 patients. Dermoscopic red lines apparent in 5/ 20 patients, of whom 4 had overused topical steroid cream. Steroid discontinued in patients with red lines and there was complete resolution within 2 mths Links compli- D ance with adverse events Study received no funding
%M: per cent male; AE(L): number local adverse events/number patients; AE(S): number systemic adverse events/number patients; AE: adverse events; BC: baseline comparability; BD: twice daily; BSA: body surface area; FU: follow up (includes TD); N: number
enrolled; NA: not applicable; NR: not reported; OD: once daily; PASI: psoriasis area and severity index; PRN: as required; TD: treatment duration; TSS: total severity score; WA: withdrawal due to adverse events
Table 25. Excluded studies of adverse events
Study Aste 2004 Bos 2002 Floden 1975 Franssen 1999
Reason for exclusion follow-up under 12 wks and not focused on adverse events not psoriasis, short review (letter) inadequate reporting of adverse events small (N = 54) retrospective study using patient questionnaires - aims to identify teratogenetic effects of tar, but many women unable to recall whether tar used in pregnancy short-term and already reected in results from main review follow-up under 12 wks and not focused on adverse events case study adverse events not reported short-term (four weeks) and brief mention of adverse events. short-term, unclear if psoriasis, small numbers (N = 6) subjects are healthy volunteers. not about adverse events. not about adverse events.
Kang 1998 Lebwohl 1996 Park 2002 Senter 1983 Singh 2000 Stevanovic 1977 Traulsen 2003 Uhoda 2003 Vissers 2004
Table 26. Included studies of compliance
Study
Methods
Participants
Interventions
Outcomes (compliance Medication adherence: (1) MEMS cap: medication bottle cap with microprocessor to record time / date of every
Summary ndings
Notes
Allocation concealme D
Balkrishnan 2003
DESIGN Uncontrolled study Patient delivery ALLOCATION: non random Method
N: 10 Topical saliTD: 1 wk; FU: cylic acid 6% 1 wk LF: 0 (0%) No control BC: NA Age: NR Gender (%M) : NR Severity: NR
MedSponsorship ication adher- not reported ence measured by method 1 (electronic) much lower than by method 2 (patient log)
535
(Continued)
of randomisation: NA. Concealment: NA BLINDING: Singleblind (patients unaware of electronic compliance assessment) WITHDRAWAL / DROPOUT: Described
INCLUSION CRITERIA: Patients with psoriasis who already enrolling in a study with salicylic acid and topical tacrolimus ointment (Protopic) combination therapy. EXCLUSION CRITERIA: NR N: 30 TD: 8 wks; FU: 12 wks LF: 6 (20%) BC: Yes Age: 43. 6 (range 18 to 70) Gender (%M) : 50% Severity: TSS (0 to 8): 5.3 INCLUSION CRITERIA: Patients aged 18; symmetrical plaquetype psoriasis; BSA <= 10%; symmetrical target plaque 1cm 2 with each with a score of at least 1 for erythema, thickness, and scale. EXCLUSION CRITERIA: Topical salicylic acid 6% plus 0. 1% tacrolimus ointment BD
opening of the bottle. (2) Patient log (self report) of compliance Mean adherence rate: method 1: 67% (32% SD); method 2: 92% (7% SD)
Carroll 2004a; Carroll 2004b; Carroll 2005
DESIGN Within patient Patient delivery ALLOCATION: random Method of randomisation: NR. Concealment: unclear BLINDING: Single-blind (patients unaware of electronic compliance assessment) WITHDRAWAL / DROPOUT: Described
Medication adherence: (1) MEMS cap: medication bottle cap with miTopical sal- croprocessor icylic acid 6% to record time plus placebo / date of every opening of the BD bottle. (2) Patient log (self report) of compliance (3) medication weights
Adherence decreased over time.On the intervention side, a decrease in adherence rate of 10% was associated with a 1-point increase in severity (P < 0. 05). For the placebotreated side, adherence was not signicantly correlated with changes in severity. Poor compliance appears to have an impact on treatment outcomes in psoriasis
Sponsored by B Fujisawa Healthcare, Inc. and by Wake Forest University School of Medicine. Excluded from effectiveness review (comparator is not placebo)
536
(Continued)
Pregnancy or risk thereof; topical treatment within previous 2 wks; phototherapy or systemic therapy within previous 4 wks
Mean adherence (method 1): % (doses taken/ doses expected): 55%; % (days with twicedaily dose/total days): 39.1% Higher adherence rate for females and older patients Impact of ofce visits on patients adherence to topical treatment. Adherence assessed using MEMS cap: medication bottle cap Adherence statistically signicantly higher at time of ofce visit. Sponsored in D part by Astellas Pharma US, Inc. The Center for Dermatology Research Mean adher- is funded by ence over the a grant from study dura- GaldermaLtion was 55%. aboratories, LP. Mean applications/day: 1.1 (range: 0.72 to (see also Balkr1.4) ishnan 2003; Carroll 2004a, 2004b, 2005)
Feldman 2007 DESIGN Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING: Single-blind (patients unaware of electronic compliance assessment) WITHDRAWAL / DROPOUT: Described Ferrandiz 1998 DESIGN Between patient Patient delivery (therapy) Clinician delivery (pro-
N: 29 6% salicylic TD: 8 wks; acid gel BD FU: 8 wks LF: NR No control BC: NA Age: 43.5 Gender (%M) : NR Severity: NR INCLUSION CRITERIA: NR EXCLUSION CRITERIA: NR
N: 881 TD: 16 wks; FU: 16 wks LF: 127 (12. 6%) BC: Yes Age: 43.3 (16.
Calcipotriol plus reinforcement programme Cal-
Reinforcement therapeutic programme to enhance adherence: derma-
The reinforce- Sponsorship ment pro- not reported gramme had no effect on treatment efcacy
537
(Continued)
gramme) ALLOCATION: random Method of randomisation: NR Concealment: unclear BLINDING: Open WITHDRAWAL / DROPOUT: Described
9SD) Gender (%M) : NR Severity: mean PASI: 7.0 INCLUSION CRITERIA: Moderately severe chronic plaque psoriasis; BSA <= 30%; aged 18 to 70; under specialist supervision. EXCLUSION CRITERIA: Pregnancy or lactation; history of intolerance to calcipotriol/ excipients; concurrent vitamin D (> 400 units/day) or calcium tablets; psoriasis mainly on face or hirsute areas
cipotriol without reinforcement programme
tologist provided patient education with explanation of disease characteristics and treatment efcacy and application, plus written information card
Fouere 2005
DESIGN Questionnaire survey (observational cross sectional study) ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING:
N: 1281 Any antipsoriTD: NA; FU: atic therapy NA LF: NA BC: NA Age: 51.9 (SD 14.8) Gender (%M) : 48% Severity: 74% considered their psoriasis as at least moderately severe
Compliance measured against PMAQ-3w scale (patient medication adherence questionnaire) : strict adherence to prescribed regimen over previous 3 days and last week-
73% reported non-compliance with current treatment.
Sponsorship not reported.
70% of responders used topMain reasons ical therapy for non-compliance: lack of efcacy, messiness and time constraints. To im538
(Continued)
Open WITHDRAWAL / DROPOUT: response rate not reported
INCLUSION CRITERIA: Members of the national psoriasis patient associations in France, UK, Belgium, Germany and the Netherlands. EXCLUSION CRITERIA: Not stated N: 109 TD: 8 wks; FU: 8 wks LF: 6 (6%) BC: NA Age: 40 (range: 16 to 70) Gender (%M) : 43% Severity: PASI: 9.1 (range: 1.2 to 35) INCLUSION CRITERIA: Chronic plaque psoriasis; received prescribed antipsoriatic therapy; aged 16; attending outpatient clinic in Istanbul. EXCLUSION CRITERIA: Other types of psoriasis; hospitalised; pregnancy
end. Reasons for noncompliance Perceived necessary measures to increase compliance
prove compliance, patients suggested improved efcacy, less greasy, sticky and smelly treatment and fewer side effects
Gokdemir 2008
DESIGN Open uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described
Any pre- Medication scribed antip- adsoriatic ther- herence: numapy ber prescribed doses taken / number prescribed doses prescribed (see Zaghoul 2004)
Mean adherence for topical therapy: 72% (31%SD).
Findings relate D to any treatment for psoriasis (not just topical therapy).
Adherence rate was corre- Sponsorship lated not reported with being unmarried, more highly educated and being satised with treatment. Main reasons for non-adherence were busyness and being fed up
539
(Continued)
Richards 1999 DESIGN Questionnaire survey (cross sectional uncontrolled study) Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Response rate not reported
N: 120 Any antipsoriTD: NA; FU: atic therapy NA LF: NA BC: NA Age: 49 (18 to 84) Gender (%M) : 54% Severity: Duration: range: 1 to 63 yrs INCLUSION CRITERIA: Consecutive patients attending tertiary psoriasis specialty clinic; psoriasis. EXCLUSION CRITERIA: Not stated
% complying with treatment (self report): scale not reported
39% reported non-compliance (sometimes/ never complying) with prescribed treatment. The noncompliant group had a higher selfrated disease severity, were younger, and had a younger age at onset. The noncompliant group reported that psoriasis had a greater impact on daily life. Factors affecting compliance included the doctor-patient relationship; optimism with the treatment prescribed; and a limited nuisance value of treatment in terms of side-effects and hassle of use 29% of responders reported that the prescriber did not specify dosage frequency. Where dosage
Sponsorship not reported. 55% of patients were using topical therapies.
van de DESIGN Kerkhof 1998 Questionnaire survey (uncontrolled study) Patient delivery ALLOCATION:
N: 972 Any top- % complying TD: NA; FU: ical antipsori- with freNA atic therapy quency of appliResponse rate: cation of pre13% scribed topical BC: NA therapies Age: 45.8 (range: 5 Reason to 87)
Sponsorship not reported. 14-item questionnaire mailed in 1996 to 6100 subscribers of
540
(Continued)
non random Method of randomisation: NA. Concealment: NABLINDING: NA WITHDRAWAL / DROPOUT: Response rate reported
Gender (%M) : 43% Severity: duration of psoriasis >10 yrs in 67% of responders. INCLUSION CRITERIA: Subscribers to Psoriasis, the journal of the Dutch Psoriasis Patient Organisation EXCLUSION CRITERIA: None stated N: 839 TD: NA; FU: NA LF: NA Response rate: 14% BC: NA Age: 48.5 (range: 4 to 91) Gender (%M) : 46% Severity: duration of psoriasis 11 years in 62% of responders INCLUSION CRITERIA: Subscribers to Psoriasis, the journal of the Dutch Psoriasis Patient Organisation EXCLUSION Any antipsoriatic therapy including topical treatments, photo (chemo)therapy and systemic therapy
for non com- frequency was pliance specied, 33% (39%) complied with twice (once) daily regimens.
Psoriasis, the journal of the Dutch Psoriasis Patient Organisation.
Responders asked to report compliMain reasons on for non-ad- ance over past herence were 6 mths. preference for less frequent dosage; greasiness; lack of efcacy; and higherthan expected efcacy % complying with duration of prescribed treatment (topical therapies): 71% Sponsorship not reported. 41item questionnaire mailed to 6100 subscribers of Psoriasis, the journal of the Dutch Psoriasis Patient Organisation. D
van de DESIGN Kerkhof 2000 Questionnaire survey (uncontrolled study) ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING: Single-blind WITHDRAWAL / DROPOUT: Response rate reported
% complying with duration of prescribed treatment (topical therapies) % complying with frequency of application of prescribed treatment (topical therapies)
% complying with frequency of application of prescribed treatment (topical therapies): Responders 51% asked to report Reason on complifor non com- Main reasons ance over past pliance for non-ad- 6 mths. herence were preference for minimum dosage; time constraints; and lack of condence in ef-
541
(Continued)
CRITERIA: None stated van de DESIGN Kerkhof 2001 Within patient (see Notes). Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: NA BLINDING: Open WITHDRAWAL / DROPOUT: Described N: 976 TD: 8 wks; FU: 8 wks LF: 93 (9.5%) BC: NR Age: 45.6 (range: 7. 4 to 88.4) Gender (%M) : 52% Severity: BSA 10% in 51% of patients INCLUSION CRITERIA: Psoriasis (type NR); eligible for treatment with calcipotriol EXCLUSION CRITERIA: Concomitant topical or systemic antipsoriatic therapy; co-existing skin disorder other than psoriasis Zaghloul 2004 DESIGN Uncontrolled study Patient delivery ALLOCATION: non random Method of randomisation: NA. Concealment: N: 294 TD: 12 wks; FU: 12 wks LF: 93 (31. 6%) BC: NA Age: 45. 1 (range: 20 to 65) Gender (%M) : 44.3% Severity: NR Topical, oral or combined antipsoriatic medication. No control Medication adherence: (1) number prescribed doses taken / number prescribed doses prescribed. (2) patient self-report. Calcipotriol cream OM plus calcipotriol ointment ON Calcipotriol ointment BD Compliance: self reported number of days cream/ ointment regimen applied.
cacy
At wk 3, 72% of patients applied the regimen on most days. By wk 8, this statistic had fallen to 61%. 51% of the 309 patients with previous experience of calcipotriol ointment monotherapy reported that their compliance with the cream/ointment regimen was higher
Sponsorship not reported. Control group comprised retrospective selfreported experience of calcipotriol ointment monotherapy by 35% of patients in the intervention group
Medication adherence measured by method 1 (objective) much lower than by method 2 (patient self report). Mean rate: 60.6% Quality of Life (33.0%SD)
Authors D report no relevant nancial interests.
542
(Continued)
NA BLINDING: Single-blind (patients unaware that study focused on compliance) WITHDRAWAL / DROPOUT: Described
INCLUSION CRITERIA: psoriasis (unclear if chronic plaque only) ; aged 18 to 65; prescribed oral, topical or combined treatment. EXCLUSION CRITERIA: pregnancy, lactation, concomitant disease
(DLQI)(0 to 30; higher score implies lower quality of life)
; (range: 0% to169%) Direct correlation observed btw medication adherence and quality of life. Adherence rate higher for patients who were female, married, employed or not paying for prescriptions. Adherence greater for topical (vs. systemic) therapy, once daily, or rst time use
%M: per cent male; AE(L): number local adverse events/number patients; AE(S): number systemic adverse events/number patients; AE: adverse events; BC: baseline comparability; BD: twice daily; BSA: body surface area; FU: follow up (includes TD); N: number enrolled; NA: not applicable; NR: not reported; OD: once daily; PASI: psoriasis area and severity index; PRN: as required; TD: treatment duration; TSS: total severity score; WA: withdrawal due to adverse events
Table 27. Excluded studies of compliance
Study Atkinson 2004 Chu 2000 Gupta 2007 Lee 2006 Osborne 2002 Richards 2006
Reason for exclusion adherence not assessed treatment guideline (not primary study) Review /think piece Review Study focuses on non responsive patients rather than those that are specically non-compliant Review
543
Table 27. Excluded studies of compliance
(Continued)
Szeimies 2004
think piece (not primary study)
APPENDICES Appendix 1. Specialised Skin Register search strategy (RCTs)

Searched 04/12/04 Search updated on 17/11/2008: from January 2005 to date 1st part (*psorias* or *psoriat*) AND (*tar* or *gel* or alphosyl or carbodome or exorex or balneum or cocois or capasal or ceanel or ionil or meted or pentrax or anthralin or dithr* or micanol or psorin or psoriderm or salicylic or (vitamin and D) or calcipo* or dovo* or *calcit* or curatoderm or tazarotene or zorac or silkis or acitretin or neotigason or ciclosporin or cyclosporin or methotrexate or tacrolimus or pimecrolimus or protopic or elidel or retinoid* or macrolactam* or immunosuppressant*) AND topical* 2nd part (*psorias* or *psoriat*) AND ((adrenal and cortex and hormone*) or *steroid* or hydrocort* or cobadex or efcortelan or *derm or *dermal or *movate or mildison or calmurid or locoid or alclometasone or modrasone or beclo* or betametha* or betacap or betnovate or bettamousse or dipro* or clobetaso* or desox* or stiedex or diucortolone or nerisone or uocino* or synalar or metosyn or uocortolone or ultralanum or urandrenolone or udroxycortide or haelan or uticasone or cutivate or halci* or mometasone or elocon or triamcinolone or *cort or *cortyl)
Appendix 2. EMBASE (OVID) search strategy (RCTs)

EMBASE (OvidSP Online http://www.ovid.com/): database updates 2002/08 to 2005/08 Search updated on 17/11/2008: 1980 to 2008 Week 46 1. Coal Tar/ 2. dithranol/ or tazarotene/ or 22 Oxacalcitriol/ 3. (coal tar or alphosyl or carbo dome or clinitar or exorex or cocois or T gel or capasal or ceanel or ionil or meted or pentrax).ti,ab. 4. (gelcosal or gelcotar or pragmatar or psoriderm or psorigel or balneum or polytar or tarcortin or dithranol or dithrocream).ti,ab. 5. (anthralin or micanol or psorin or salicylic acid$ or vitamin d analogue$ or vitamin d derivative$).ti,ab. 6. (calcipotriol or calcipotriene or dovonex or dovobet or tacalcitol or curatoderm or tazarotene or zorac or silkis or maxacalcitol).ti,ab. 7. vitamin d derivative/ or calcipotriol/ or calcitriol/ or tacalcitol/ or Salicylic Acid/ 8. or/1-7 9. Etretin/ or Immunosuppressive Agent/ or Tacrolimus/ 10. Cyclosporin/ or Retinoid/ or Pimecrolimus/ 11. Methotrexate/ 12. ((immunosuppressant$ or acitretin or neotigason or cyclosporin$ or ciclosporin$ or methotrexate or retinoid$ or macrolactam) adj5 topical$).ti,ab. 13. ((tacrolimus or protopic or pimecrolimus or elidel) adj5 topical$).ti,ab. 14. or/9-11 15. topical.ti,ab. or topical treatment/ or topical drug administration/ 16. (14 and 15) or 12 or 13 17. exp Corticosteroid/ 18. Hydrocortisone/ 19. (corticosteroid$ or cortico steroid$ or hydrocortisone or cobadex or dioderm or efcortelan).ti,ab.
20. (hydrocortisyl or mildison or alphaderm or calmurid).ti,ab. 21. (locoid or modrasone or beclomethasone dipropionate).ti,ab. 22. (alclometasone diproprionate or propaderm or betamethasone or betacap or betnovate or diprosone).ti,ab. 23. (diprosalic or bettamousse or clobetasol propionate or dermovate or clobetasone butyrate).ti,ab. 24. (eumovate or trimovate or desoxymethasone or desoxymetasone or desoximethasone or desoximetasone or stiedex).ti,ab. 25. (diucortolone valerate or nerisone or uocinolone acetonide or synalar or uocinonide or metosyn).ti,ab. 26. (ultralanum or urandrenolone or haelan or uticasone propionate or cutivate or halcinonide or halciderm).ti,ab. 27. (mometasone furoate or elocon or adcortyl or aureocort or nystadermal or tri adcortyl or steroid$).ti,ab. 28. beclometasone/ or psoralon/ or psoraderm/ or psoradexan/ or psorin/ 29. Beclometasone Dipropionate/ or Urea/ or hydrocortisone butyrate/ or hydrocortisone plus urea/ 30. alclometasone dipropionate/ or betamethasone dipropionate/ or betamethasone valerate/ or diucortolone/ 31. clobetasol propionate/ or clobetasone butyrate/ or desoximetasone/ or diucortolone valerate/ or uocinonide/ or Fluticasone Propionate/ 32. uocinolone/ or halcinonide/ or mometasone furoate.mp. or triamcinolone acetonide/ 33. Fluocortolone/ 34. Fludroxycortide/ 35. Triamcinolone/ 36. exp Steroid/ 37. exp Steroid Hormone/ 38. or/17-37 39. exp Antipsoriasis Agent/ 40. 8 or 16 or 38 or 39 41. exp Psoriasis/ 42. (psorias$ or psoriat$ or antipsorias$ or antipsoriat$).ti,ab. 43. or/41-42 44. 40 and 43 45. randomization/ 46. Single Blind Procedure/ 47. Double Blind Procedure/ 48. exp clinical trial/ 49. Placebo/ 50. Methodology/ 51. comparative study/ 52. exp drug comparison/ 53. evaluation/ 54. Follow Up/ 55. Prospective Study/ 56. Crossover Procedure/ 57. (clinical$ adj3 (trial$ or study or studies)).ti,ab. 58. (intervention$ adj3 (trial$ or study or studies)).ti,ab. 59. ((single$ or doubl$ or trebl$ or tripl$) adj3 blind$).ti,ab. 60. ((single$ or doubl$ or trebl$ or tripl$) adj3 mask$).ti,ab. 61. (placebo or placebos or random$ or control$ or prospectiv$ or volunteer$).ti,ab. 62. or/45-61 63. 44 and 62 64. (200600 or 200500 or 200700).em. 65. 2008$.em. 66. 64 or 65 67. 63 and 66
545
Appendix 3. MEDLINE (OVID) search strategy (RCTs)

MEDLINE (OvidSP Online http://www.ovid.com/): database updates 2002/07 to 2005/02 week 2 Search updated on 17/11/2008: 1950 to November Week 1 2008 1. randomized controlled trial.pt. 2. randomized controlled trial/ 3. Random Allocation/ 4. Double-Blind Method/ 5. single-blind method/ 6. clinical trial.pt. 7. exp clinical trial/ 8. ((clinical$ or intervention$) adj5 (trial$ or study or studies)).tw. 9. ((singl$ or doubl$ or trebl$ or tripl$) adj5 (blind$ or mask$)).tw. 10. Placebos/ 11. (placebo$ or random$).tw. 12. Research Design/ 13. Comparative Study/ 14. exp evaluation studies as topic/ 15. Follow-Up Studies/ 16. Prospective Studies/ 17. (control$ or prospectiv$ or volunteer$).tw. 18. Animals/ 19. Humans/ 20. or/1-17 21. 8 not (18 and 19) 22. 20 not 21 23. exp Psoriasis/ 24. psorias$.tw. 25. psoriat$.tw. 26. or/23-25 27. coal tar/ 28. coal tar.tw. 29. alphosyl.tw. 30. carbo dome.tw. 31. clinitar.tw. 32. exorex.tw. 33. gelcosal.tw. 34. gelcotar.tw. 35. pragmatar.tw. 36. psorigel.tw. 37. balneum.tw. 38. polytar.tw. 39. psoriderm.tw. 40. tarcortin.tw. 41. cocois.tw. 42. (T adj gel).tw. 43. capasal.tw. 44. ceanel.tw. 45. clinitar.tw. 46. ionil.tw. 47. meted.tw. 48. pentrax.tw. 49. Anthralin/
50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102.
dithranol.tw. dithrocream.tw. micanol.tw. psorin.tw. salicylic acid$.tw. (vitamin adj d adj2 analogue$).tw. (vitamin adj d adj2 derivative$).tw. calcipotriol.tw. calcipotriene.tw. dovonex.tw. dovobet.tw. tacalcitol.tw. curatoderm.tw. tazarotene.tw. zorac.tw. Calcitriol/ silkis.tw. maxacalcitol.tw. or/27-67 Acitretin/ acitretin.tw. neotigason.tw. exp Cyclosporins/ cyclosporin.tw. ciclosporin.tw. Methotrexate/ methotrexate.tw. Tacrolimus/ tacrolimus.tw. protopic.tw. pimecrolimus/ pimecrolimus.tw. elidel.tw. or/69-82 topical.tw. 83 and 84 topical retinoid$.tw. topical macrolactam$.tw. topical immunosuppressant$.tw. or/85-88 68 or 89 antipsoriat$.tw. antipsorias$.tw. 26 or 91 or 92 exp Psoriasis/th, pc, dt [Therapy, Prevention & Control, Drug Therapy] Dermatologic Agents/ 93 and 22 94 and 22 95 and 93 and 22 or/96-98 exp Adrenal Cortex Hormones/ corticosteroid$.tw. cortico steroid$.tw.
547
103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118. 119. 120. 121. 122. 123. 124. 125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155.
exp Hydrocortisone/ hydrocortisone.tw. cobadex.tw. dioderm.tw. efcortelan.tw. hydrocortisyl.tw. mildison.tw. alphaderm.tw. calmurid.tw. hydrocortisone butyrate.tw. locoid.tw. alclometasone dipropionate.tw. modrasone.tw. Beclomethasone/ beclomet$asone dipropionate.tw. propaderm.tw. exp Betamethasone/ betamethasone esters.tw. betamethasone.tw. betacap.tw. betnovate.tw. diprosone.tw. diprosalic.tw. bettamousse.tw. clobetasol propionate.tw. dermovate.tw. clobetasone butyrate.tw. eumovate.tw. trimovate.tw. Desoximetasone/ desoxymethasone.tw. desoximetasone.tw. stiedex.tw. Diucortolone/ diucortolone valerate.tw. nerisone.tw. exp Fluocinolone Acetonide/ uocinolone acetonide.tw. synalar.tw. uocinonide.tw. metosyn.tw. exp Fluocortolone/ uocortolone.tw. ultralanum.tw. Flurandrenolone/ urandrenolone.tw. udroxycortid$.tw. haelan.tw. uticasone propionate.tw. cutivate.tw. halcinonide.tw. halciderm.tw. mometasone furoate.tw.
548
156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174.
elocon.tw. exp Triamcinolone/ triamcinolone acetonide.tw. adcortyl.tw. aureocort.tw. nystadermal.tw. tri-adcortyl.tw. exp Steroids/ steroid$.tw. or/100-164 22 and 93 and 165 22 and 93 and 90 99 or 166 or 167 200502$.ed. 2006$.ed. 2007$.ed. 2008$.ed. or/169-172 168 and 173
Appendix 4. Science Citation Index (ISI web of Knowledge interface) search strategy (RCTs)
Science Citation Index (SCI Web Of Knowledge http://wos.mimas.ac.uk/): publication years 2000 to 2005 Search updated on 17/11/2008: All lines linted as follows: DocType=All document types; Language=All languages; Database=SCI EXPANDED; Timespan=2005-2008 #1 Topic=((psoria* OR antipsoria*) AND (trial* OR random* OR control OR controls OR double blind OR doubleblind or single blind OR singleblind OR placebo* or evaluation*)) #2 Topic=(coaltar or coal tar or alphosyl or carbo dome or clinitar or exorex or gelcosal or gelcotar or pragmatar) #3 Topic=(psorigel or balneum or polytar or psoriderm or tarcortin or cocois or t gel or tgel or capasal or ceanel or clinitar or ionil or meted or pentrax) #4 Topic=(eumovate or trimovate or desoxime$asone or desoxyme$asone or stiedex or diucortolone or nerisone or uocinolone or synalar) #5 Topic=(anthralin OR dithranol or dithrocream or micanol or psorin or salicylic acid or salicylic acids or vitamin d or calcipotriol or calcipotriene or dovonex or dovobet or tacalcitol or curatoderm or tazarotene or zorac) #6 Topic=(uocinonide or metosyn or uocortolone or ultralanum or urandrenolone or udroxycortide or haelan or uticasone propionate) #7 Topic=(calcitriol or silkis or maxacalcitol) #8 Topic=(cutivate or halcinonide or halciderm or mometasone furoate or elocon or triamcinolone or adcortyl or aureocort or nystadermal or triadcortyl or steroid or steroids or steroidal) #9 Topic=((acitretin or neotigason or cyclosporin* or ciclosporin* or methotrexate or tacrolimus or protopic or pimecrolimus or elidel or retinoid* or macrolactam* or immunosuppressant*) same topical) # 10 Topic=(adrenal cortex hormone* or corticosteroid* or cortico steroid* or hydrocortisone or cobadex or dioderm or efcortelan or hydrocortisyl or mildison) # 11 Topic=(alphaderm or calmurid or locoid or alclometasone dipropionate or modrasone or beclomet$asone or propaderm) # 12 Topic=(betamethasone or betacap or betnovate or diprosone or diprosalic or bettamousse or clobetasol propionate or dermovate or clobetasone butyrate) # 13 #12 OR #11 OR #10 OR #9 OR #8 OR #7 OR #6 OR #5 OR #4 OR #3 OR #2 # 14 #13 AND #1
549
Appendix 5. Biosis (EDINAinterface) search strategy (RCTs)

Biosis (EDINAinterface): publication years 2001 to 2005 Search updated on 17/11/2008: Accessed via Dialog (le 55) using Dialog Classic Web (see Appendix 6) ((((((((((((((al: betamethasone or betacap or betnovate or diprosone or diprosalic or bettamousse or clobetasol propionate or dermovate or clobetasone butyrate) and (sy: 2001-2005)) or ((al: alphaderm or calmurid or locoid or alclometasone dipropionate or modrasone or beclomethasone beclometasone or propaderm) and (sy: 2001-2005))) or ((al: adrenal cortex hormone* or corticosteroid* or cortico steroid* or hydrocortisone or cobadex or dioderm or efcortelan or hydrocortisyl or mildison) and (sy: 2001-2005))) or ((al: (acitretin or neotigason or cyclosporin* or ciclosporin* or methotrexate or tacrolimus or protopic or pimecrolimus or elidel or retinoid* or macrolactam* or immunosuppressant*)) and (sy: 2001-2005))) or ((al: cutivate or halcinonide or halciderm or mometasone furoate or elocon or triamcinolone or adcortyl or aureocort or nystadermal or triadcortyl or steroid or steroids or steroidal) and (sy: 2001-2005))) or ((al: (calcitriol or silkis or maxacalcitol)) and (sy: 2001-2005))) or ((al: uocinonide or metosyn or uocortolone or ultralanum or urandrenolone or udroxycortide or haelan or uticasone propionate) and (sy: 2001-2005))) or ((al: anthralin OR dithranol or dithrocream or micanol or psorin or salicylic acid or salicylic acids or vitamin d or calcipotriol or calcipotriene or dovonex or dovobet or tacalcitol or curatoderm or tazarotene or zorac) and (sy: 2001-2005))) or ((al: (eumovate or trimovate or desoxime$asone or desoxyme$asone or stiedex or diucortolone or nerisone or uocinolone or synalar)) and (sy: 2001-2005))) or (al: (psorigel or balneum or polytar or psoriderm or tarcortin or cocois or t gel or tgel or capasal or ceanel or clinitar or ionil or meted or pentrax))) or (al: (coaltar or coal tar or alphosyl or carbo dome or clinitar or exorex or gelcosal or gelcotar or pragmatar)))) and ((((al: trial* or random* or double blind or doubleblind or single blind or singleblind or evaluation* or placebo* or control or controls) and (sy: 20012005)) and ((al: (psoria* or antipsoria*)) and (sy: 2001-2005)))))
Appendix 6. Dissertation Abstracts (Dialog Classic interface) and Inside Conferences (Dialog Classic interface) search strategies (RCTs)
Dissertation Abstracts (Dialog Classic interface): all publication years Inside Conferences (Dialog Classic interface): all publication years Searches updated on 17/11/2008: Biosis: Accessed via Dialog (le 55) using Dialog Classic Web Dissertation Abstracts: Accessed via Dialog (le 35) using Dialog Classic Web Inside Conferences: Accessed via Dialog (le 65) using Dialog Classic Web 1. s (coal()tar or coaltar or alphosyl or carbo()dome or clinitar or exorex or cocois)/ti,ab,de 2. s (t()gel or tgel or capasal or ceanel or clinitar or ionil or meted or pentrax)/ti,ab,de 3. s (dithranol or gelcosal or gelcotar or pragmatar or psoriderm or psorigel or balneum or 4. polytar or tarcortin or dithrocream)/ ti,ab,de 4. s (micanol or psorin or salicylic()acid? ? or vitamin()d()analogue? or vitamin()d()derivative?)/ti,ab,de 5. s (calcipotriol or calcipotriene or dovonex or dovobet or tacalcitol or curatoderm or tazarotene or zorac)/ti,ab,de 6. s (calcitriol or silkis or maxacalcitol or adrenal()cortex()hormone? ?)/ti,ab,de 7. s ((cyclosporin or ciclosporin or methotrexate or acitretin or neotigason)(4w)topical?)/ti,ab,de 8. s ((retinoid? ? or immunosuppressant? ? or tacrolimus or protopic or pimecrolimus or macorlactam? ?)(4w)topical?)/ti,ab,de 9. s (corticosteroid? ? or cortico()steroid? ? or hydrocortisone or cobadex or dioderm or efcortelan)/ti,ab,de 10. s (hydrocortisyl or mildison or alphaderm or calmurid)/ti,ab,de 11. s (locoid or alclometasone()dipropionate or modrasone or beclomethasone()dipropionate)/ti,ab,de 12. s (propaderm or betamethasone or betacap or betnovate or diprosone)/ti,ab,de 13. s (diprosalic or bettamousse or clobetasol()propionate or dermovate or clobetasone()butyrate)/ti,ab,de 14. s (eumovate or trimovate or desoxymethasone or desoxymetasone or desoximetasone or desoximethasone or stiedex)/ti,ab,de 15. s (diucortolone()valerate or nerisone or uocinolone()acetonide or synalar or uocinonide or metosyn)/ti,ab,de 16. s (uocortolone or ultralanum or haelan or uticasone()propionate or cutivate or halcinonide or halciderm or urandrenolone or triamcinolone)/ti,ab,de 17. s (mometasone()furoate or elocon or adcortyl or aureocort or nystadermal or triadcortyl or steroid? ? or steroidal)/ti,ab,de 18. s (beclometasone()dipropionate or udroxycortide or triamcinolone)/ti,ab,de 19. s (psoria? or antipsoria?)/ti,ab,de 20. s (random? or single()blind or singleblind or double()blind or doubleblind)/ti,ab,de 21. s (placebo or comparative()study or evaluation or prospective()study or crossover or trial or trials or triallist? ?)/ti,ab,de
22. 23. 24. 25. 26. 27. 28. 29.
s (control or controls? or prospectiv?)/ti,ab,de s s1:s18 s s23 and s19 s s20:s22 s s24 and s25 s UD=200503:200812 s s26 and s27 s rd s28
Appendix 7. SIGLE (WebSPIRS interface) search strategy (RCTs)

SIGLE (WebSPIRS interface): publication years 2001 to 2005 (database issue 2004/12) SIGLE has not been updated since 2005, so searches were not rerun in 2008. #1 psoriat* or psorias*(83 records) #2 (2002 in PY) or (2003 in PY) or (2004 in PY) or (2005 in PY)(49881 records) #3 ((2002 in PY) or (2003 in PY) or (2004 in PY) or (2005 in PY)) and (psoriat* or psorias*)(5 records)
Appendix 8. CENTRAL (Cochrane Library CD-ROM) and National Research Register (NRR) (CDROM interface) search strategies (RCTs)
CENTRAL (Cochrane Library CD-ROM 2005 issue 1): publication years 2001 to 2005-02-24 National Research Register (CD-ROM interface, issue 2004/4): all projects with a start date of 2001 to 2005 Searches updated in 2008: Searched on 20/11/08: UK Clinical Research Network Study Portfolio (http://public.ukcrn.org.uk/search/) (NRR no longer in existence) Website was browsed Searched on 17/11/08: CENTRAL (The Cochrane Library: http://www.thecochranelibrary.com/). #1 MeSH descriptor Psoriasis explode all trees #2 (Psorias* or psoriat* or antipsoria*) #3 MeSH descriptor Coal Tar, this term only #4 coal tar #5 (alphosyl) #6 carbo dome #7 (clinitar or exorex or gelcosal or gelcotar) #8 (pragmatar or psorigel or balneum or polytar) #9 (psoriderm or tarcortin or cocois) #10 T gel #11 (capasal or ceanel or clinitar or ionil) #12 (meted or pentrax) #13 MeSH descriptor Anthralin, this term only #14 (Dithranol or dithrocream or micanol or psorin) #15 (salicylic next acid*) #16 (vitamin next d next analogue*) #17 (vitamin next d next derivative*) #18 (calcipotriol or calcipotriene or dovonex or dovobet) #19 (tacalcitol or curatoderm or tazarotene or zorac) #20 MeSH descriptor Calcitriol, this term only #21 (silkis or maxacalcitol) #22 (#3 OR #4 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR # 17 OR #18 OR #19 OR #20 OR #21) #23 MeSH descriptor Acitretin, this term only #24 (acitretin or neotigason or cyclosporin or ciclosporin)
#25 #26 #27 #28 #29 #30 #31 #32 #33 #34 #35 #36 #37 #38 #39 #40 #41 #42 #43 #44 #45 #46 #47 #48 #49 #50 #51 #52 #53 #54 #55 #56 #57 #58 #59 #60 #61 #62 #63 #64 #65 #66 #67 #68 #69 #70 #71 #72 #73 #74 #75 #76 #77
MeSH descriptor Cyclosporins explode all trees MeSH descriptor Methotrexate, this term only MeSH descriptor Tacrolimus, this term only (methotrexate or tacrolimus or pimecrolimus or elidel or protopic) (PIMECROLIMUS) (#23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29) (topical) (#30 AND #31) (topical next retinoid*) (topical next macrolactam*) (topical next immunosuppressant*) MeSH descriptor Dermatologic Agents, this term only MeSH descriptor Adrenal Cortex Hormones explode all trees (corticosteroid* or (cortico next steroid*)) MeSH descriptor Hydrocortisone explode all trees (hydrocortisone or cobadex or dioderm or efcortelan or hydrocortisyl mildison or alphaderm or calmurid) hydrocortisone butyrate alclometasone dipropionate (modrasone or locoid or propaderm) MeSH descriptor Beclomethasone, this term only beclomethasone dipropionate MeSH descriptor Betamethasone explode all trees betamethasone esters (betamethasone or betacap or betnovate or diprosone) (diprosalic or bettamousse) clobetasol propionate clobetasone butyrate (eumovate or trimovate or dermovate) MeSH descriptor Desoximetasone, this term only (desoxymethasone or desoximetasone or stiedex) MeSH descriptor Diucortolone, this term only diucortolone valerate MeSH descriptor Fluocinolone Acetonide explode all trees uocinolone acetonide (synalar or uocinonide or metosyn or nerisone or elocon) MeSH descriptor Fluocortolone explode all trees (uocortolone or ultralanum or urandrenolone or haelan) MeSH descriptor Flurandrenolone, this term only (FLUDROXYCORTIDE) (uticasone next propionate) (cutivate or halcinonide or halciderm) mometasone furoate MeSH descriptor Triamcinolone explode all trees triamcinolone acetonide (adcortyl or aureocort or nystadermal or triadcortyl) MeSH descriptor Steroids explode all trees (steroid*) (#33 OR #34 OR #35 OR #36 OR #37 OR #38 OR #39 OR #40) (#41 OR #42 OR #43 OR #44 OR #45 OR #46 OR #47 OR #48) (#49 OR #50 OR #51 OR #52 OR #53 OR #54 OR #55 OR #56) (#57 OR #58 OR #59 OR #60 OR #61 OR #62 OR #63 OR #64) (#65 OR #66 OR #67 OR #68 OR #69 OR #70 OR #71) (#22 OR #32 OR #72 OR #73 OR #74 OR #75 OR #76)
552
#78
(( #1 OR #2 ) AND #77), from 2005 to 2008
Appendix 9. EMBASE (OVID) search strategy (adverse events)

EMBASE (OvidSP Online http://www.ovid.com/): 1990 to 2005/08 Search updated on 11/12/2008: 1980 to 2008 Week 49 Note: A pragmatic approach was taken to reduce irrelevant records and to negate the over indexing of records in EMBASE; EMTREE terms were focussed in this strategy 1. (coal adj tar).ti,ab. 2. alphosyl.ti,ab. 3. (carbo adj dome).ti,ab. 4. clinitar.ti,ab. 5. exorex.ti,ab. 6. gelcosal.ti,ab. 7. gelcotar.ti,ab. 8. pragmatar.ti,ab. 9. psorigel.ti,ab. 10. balneum.ti,ab. 11. polytar.ti,ab. 12. psoriderm.ti,ab. 13. tarcortin.ti,ab. 14. cocois.ti,ab. 15. (T adj gel).ti,ab. 16. capasal.ti,ab. 17. ceanel.ti,ab. 18. ionil.ti,ab. 19. meted.ti,ab. 20. pentrax.ti,ab. 21. dithranol.ti,ab. 22. dithrocream.ti,ab. 23. micanol.ti,ab. 24. psorin.ti,ab. 25. (salicylic adj acid$).ti,ab. 26. (vitamin adj d adj2 analogue$).ti,ab. 27. (vitamin adj d adj2 derivative$).ti,ab. 28. calcipotriol.ti,ab. 29. calcipotriene.ti,ab. 30. dovonex.ti,ab. 31. dovobet.ti,ab. 32. tacalcitol.ti,ab. 33. curatoderm.ti,ab. 34. tazarotene.ti,ab. 35. zorac.ti,ab. 36. silkis.ti,ab. 37. maxacalcitol.ti,ab. 38. antipsoriat$.ti,ab. 39. antipsorias$.ti,ab. 40. corticosteroid$.ti,ab. 41. (cortico adj steroid$).ti,ab. 42. hydrocortisone.ti,ab. 43. cobadex.ti,ab. 44. dioderm.ti,ab.
45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97.
efcortelan.ti,ab. hydrocortisyl.ti,ab. mildison.ti,ab. alphaderm.ti,ab. calmurid.ti,ab. (hydrocortisone adj butyrate).ti,ab. locoid.ti,ab. (alclometasone adj dipropionate).ti,ab. modrasone.ti,ab. (beclomet$asone adj dipropionate).ti,ab. propaderm.ti,ab. (betamethasone adj esters).ti,ab. betamethasone.ti,ab. betacap.ti,ab. betnovate.ti,ab. diprosone.ti,ab. diprosalic.ti,ab. bettamousse.ti,ab. (clobetasol adj propionate).ti,ab. dermovate.ti,ab. (clobetasone adj butyrate).ti,ab. eumovate.ti,ab. trimovate.ti,ab. desoxymethasone.ti,ab. desoximetasone.ti,ab. stiedex.ti,ab. (diucortolone adj valerate).ti,ab. nerisone.ti,ab. (uocinolone adj acetonide).ti,ab. synalar.ti,ab. uocinonide.ti,ab. metosyn.ti,ab. uocortolone.ti,ab. ultralanum.ti,ab. urandrenolone.ti,ab. haelan.ti,ab. (uticasone adj propionate).ti,ab. cutivate.ti,ab. halcinonide.ti,ab. halciderm.ti,ab. (mometasone adj furoate).ti,ab. elocon.ti,ab. (triamcinolone adj acetonide).ti,ab. adcortyl.ti,ab. aureocort.ti,ab. nystadermal.ti,ab. tri-adcortyl.ti,ab. steroid$.ti,ab. *Coal Tar/ *alphosyl/ *carbo dome/ *Salicylic Acid/ *capasal/
554
98. *meted/ 99. *Dithranol/ 100. *Psorin/ 101. *Vitamin d Derivative/ 102. *Calcipotriol/ 103. *Betamethasone Dipropionate Plus Calcipotriol/ 104. *Tacalcitol/ 105. *Tazarotene/ 106. *Calcitriol/ 107. *22 Oxacalcitriol/ 108. *Corticosteroid/ 109. *Hydrocortisone/ 110. *Urea/ 111. *Hydrocortisone Butyrate/ 112. *Alclometasone Dipropionate/ 113. *Beclometasone Dipropionate/ 114. *Betamethasone/ 115. *Betamethasone Valerate/ 116. *Betamethasone Dipropionate/ 117. *Clobetasol Propionate/ 118. *Clobetasone Butyrate/ 119. *trimovate/ 120. *Desoximetasone/ 121. *Diucortolone Valerate/ 122. *Fluocinolone Acetonide/ 123. *Fluocinonide/ 124. *Fluocortolone/ 125. *Fludroxycortide/ 126. *Fluticasone Propionate/ 127. *Halcinonide/ 128. *Mometasone Furoate/ 129. *Triamcinolone Acetonide/ 130. *Triamcinolone/ 131. *Mycolog/ 132. *exp Steroid/ 133. *Cyclosporin Derivative/ or *Cyclosporin/ 134. *Tacrolimus/ 135. *Dermatological Agent/ 136. or/1-135 137. *Tacrolimus/ 138. *Pimecrolimus/ 139. *Immunosuppressive Agent/ 140. *Etretin/ 141. *Cyclosporin/ 142. *Cyclosporin A/ 143. *Methotrexate/ 144. *Retinoid/ 145. or/137-144 146. topical.ti,ab. or topical treatment/ or topical drug administration/ 147. 145 and 146 148. ((tacrolimus or protopic or pimecrolimus or elidel or immunosuppressant$ or acitretin or neotigason or cyclosporin$ or ciclosporin$ or methotrexate or retinoid$ or macrolactam) adj5 topical$).ti,ab. 149. 136 or 147 or 148
150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181. 182. 183. 184. 185. 186. 187. 188. 189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202.
(safe or safety).ti,ab. side effect$.ti,ab. treatment emergent.ti,ab. undesirable effect$.ti,ab. tolerability.ti,ab. toxicity.ti,ab. adrs.ti,ab. (adverse adj3 (effect or effects or reaction or reactions or event or events or outcome or outcomes)).ti,ab. *Safety/ or *Drug Safety/ *Side Effect/ *Adverse Drug Reaction/ *Drug Tolerability/ *Toxicity/ or *Drug Toxicity/ *Drug Surveillance Program/ *Adverse Outcome/ hypersensit$.ti,ab. harm$.ti,ab. rebound.ti,ab. *Drug Hypersensitivity/ *Rebound/ *Withdrawal Syndrome/ *Hypercalcemia/ *Urolithiasis/ *Tachyphylaxis/ *Drug Withdrawal/ *Atrophy/ *Telangiectasia/ cutaneous atrophy.ti,ab. striae.ti,ab. skin atrophy.ti,ab. *Skin Atrophy/ *Stria/ or/150-181 *Coal Tar/ae, to [Adverse Drug Reaction, Drug Toxicity] *alphosyl/ae [Adverse Drug Reaction] *Salicylic Acid/ae, to [Adverse Drug Reaction, Drug Toxicity] *Dithranol/ae, to [Adverse Drug Reaction, Drug Toxicity] *Psorin/ae [Adverse Drug Reaction] *Vitamin d Derivative/ae, to [Adverse Drug Reaction, Drug Toxicity] *Calcipotriol/ae, to [Adverse Drug Reaction, Drug Toxicity] *Betamethasone Dipropionate Plus Calcipotriol/to, ae [Drug Toxicity, Adverse Drug Reaction] *Tacalcitol/ae, to [Adverse Drug Reaction, Drug Toxicity] *Tazarotene/ae, to [Adverse Drug Reaction, Drug Toxicity] *Calcitriol/ae, to [Adverse Drug Reaction, Drug Toxicity] *22 Oxacalcitriol/ae, to [Adverse Drug Reaction, Drug Toxicity] *Corticosteroid/ae, to [Adverse Drug Reaction, Drug Toxicity] *Hydrocortisone/ae, to [Adverse Drug Reaction, Drug Toxicity] *Urea/ae, to [Adverse Drug Reaction, Drug Toxicity] *Hydrocortisone Butyrate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Alclometasone Dipropionate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Beclometasone Dipropionate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Betamethasone/ae, to [Adverse Drug Reaction, Drug Toxicity] *Betamethasone Valerate/ae, to [Adverse Drug Reaction, Drug Toxicity]
556
203. 204. 205. 206. 207. 208. 209. 210. 211. 212. 213. 214. 215. 216. 217. 218. 219. 220. 221. 222. 223. 224. 225. 226. 227. 228. 229. 230. 231. 232. 233. 234. 235. 236. 237.
*Betamethasone Dipropionate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Clobetasol Propionate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Clobetasone Butyrate/ae [Adverse Drug Reaction] *trimovate/ae [Adverse Drug Reaction] *Desoximetasone/ae, to [Adverse Drug Reaction, Drug Toxicity] *Diucortolone Valerate/to, ae [Drug Toxicity, Adverse Drug Reaction] *Fluocinolone Acetonide/ae, to [Adverse Drug Reaction, Drug Toxicity] *Fluocinonide/ae, to [Adverse Drug Reaction, Drug Toxicity] *Fluocortolone/ae, to [Adverse Drug Reaction, Drug Toxicity] *Fludroxycortide/ae [Adverse Drug Reaction] *Fluticasone Propionate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Halcinonide/ae [Adverse Drug Reaction] *Mometasone Furoate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Triamcinolone Acetonide/ae, to [Adverse Drug Reaction, Drug Toxicity] *Triamcinolone/ae, to [Adverse Drug Reaction, Drug Toxicity] *Mycolog/ae [Adverse Drug Reaction] *exp Steroid/ae, to [Adverse Drug Reaction, Drug Toxicity] *Cyclosporin Derivative/ae, to [Adverse Drug Reaction, Drug Toxicity] *Cyclosporin/ae, to [Adverse Drug Reaction, Drug Toxicity] *Tacrolimus/ae, to [Adverse Drug Reaction, Drug Toxicity] *Dermatological Agent/ae, to [Adverse Drug Reaction, Drug Toxicity] *Pimecrolimus/ae, to [Adverse Drug Reaction, Drug Toxicity] *Immunosuppressive Agent/ae, to [Adverse Drug Reaction, Drug Toxicity] *Etretin/ae, to [Adverse Drug Reaction, Drug Toxicity] *Cyclosporin A/ae, to [Adverse Drug Reaction, Drug Toxicity] *Methotrexate/ae, to [Adverse Drug Reaction, Drug Toxicity] *Retinoid/ae, to [Adverse Drug Reaction, Drug Toxicity] or/183-229 182 or 230 (psorias$ or psoriat$).ti,ab. *exp Psoriasis/ 232 or 233 149 and 231 and 234 limit 235 to human limit 236 to yr=1990 - 2009
Appendix 10. MEDLINE (OVID) search strategy (adverse events)

MEDLINE (OvidSP Online http://www.ovid.com/): database updates 1990 to 2005/02 week 2 Search updated on 17/11/2008: 1950 to November Week 1 2008 1. (coal adj tar).tw. 2. alphosyl.tw. 3. (carbo adj dome).tw. 4. clinitar.tw. 5. exorex.tw. 6. gelcosal.tw. 7. gelcotar.tw. 8. pragmatar.tw. 9. psorigel.tw. 10. balneum.tw. 11. polytar.tw. 12. psoriderm.tw.
13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. 56. 57. 58. 59. 60. 61. 62. 63. 64. 65.
tarcortin.tw. cocois.tw. (T adj gel).tw. capasal.tw. ceanel.tw. ionil.tw. meted.tw. pentrax.tw. dithranol.tw. dithrocream.tw. micanol.tw. psorin.tw. (salicylic adj acid$).tw. (vitamin adj d adj2 analogue$).tw. (vitamin adj d adj2 derivative$).tw. calcipotriol.tw. calcipotriene.tw. dovonex.tw. dovobet.tw. tacalcitol.tw. curatoderm.tw. tazarotene.tw. zorac.tw. silkis.tw. maxacalcitol.tw. antipsoriat$.tw. antipsorias$.tw. corticosteroid$.tw. (cortico adj steroid$).tw. hydrocortisone.tw. cobadex.tw. dioderm.tw. efcortelan.tw. hydrocortisyl.tw. mildison.tw. alphaderm.tw. calmurid.tw. (hydrocortisone adj butyrate).tw. locoid.tw. (alclometasone adj dipropionate).tw. modrasone.tw. (beclomet$asone adj dipropionate).tw. propaderm.tw. (betamethasone adj esters).tw. betamethasone.tw. betacap.tw. betnovate.tw. diprosone.tw. diprosalic.tw. bettamousse.tw. (clobetasol adj propionate).tw. dermovate.tw. (clobetasone adj butyrate).tw.
558
66. 67. 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116. 117. 118.
eumovate.tw. trimovate.tw. desoxymethasone.tw. desoximetasone.tw. stiedex.tw. (diucortolone adj valerate).tw. nerisone.tw. (uocinolone adj acetonide).tw. synalar.tw. uocinonide.tw. metosyn.tw. uocortolone.tw. ultralanum.tw. urandrenolone.tw. haelan.tw. (uticasone adj propionate).tw. cutivate.tw. halcinonide.tw. halciderm.tw. (mometasone adj furoate).tw. elocon.tw. (triamcinolone adj acetonide).tw. adcortyl.tw. aureocort.tw. nystadermal.tw. tri-adcortyl.tw. steroid$.tw. Coal Tar/ Anthralin/ Calcitriol/ exp Cyclosporins/ Tacrolimus/ Dermatologic Agents/ exp Adrenal Cortex Hormones/ exp Hydrocortisone/ Beclomethasone/ exp Betamethasone/ Desoximetasone/ Diucortolone/ exp Fluocinolone Acetonide/ Fluocortolone/ Flurandrenolone/ Flurandrenolone/ exp Triamcinolone/ exp Steroids/ or/1-110 Acitretin/ Immunosuppressive Agents/ Cyclosporine/ Retinoids/ Methotrexate/ or/112-116 topical.ti,ab. or topical treatment/ or topical drug administration/
559
119 117 and 118 120. ((tacrolimus or protopic or pimecrolimus or elidel or immunosuppressant$ or acitretin or neotigason or cyclosporin$ or ciclosporin$ or methotrexate or retinoid$ or macrolactam) adj5 topical$).tw. 121. 119 or 120 or 111 122. (safe or safety).tw. 123. side effect$.tw. 124. treatment emergent.tw. 125. undesirable effect$.tw. 126. tolerability.tw. 127. toxicity.tw. 128. adrs.tw. 129. (adverse adj3 (effect or effects or reaction or reactions or event or events or outcome or outcomes)).tw. 130. Adverse Drug Reaction Reporting Systems/ 131. drug hypersensitivity/ 132. hypersensit$.tw. 133. harm$.tw. 134. exp Substance Withdrawal Syndrome/ci [Chemically Induced] 135. rebound.tw. 136. Hypercalcemia/ci [Chemically Induced] 137. exp Urinary Calculi/ci [Chemically Induced] 138. Tachyphylaxis/ci, de [Chemically Induced, Drug Effects] 139. exp Substance Withdrawal Syndrome/ci [Chemically Induced] 140. exp Atrophy/ci [Chemically Induced] 141. exp Telangiectasis/ci [Chemically Induced] 142. cutaneous atrophy.tw. 143. striae.tw. 144. skin atrophy.tw. 145. exp Abnormalities, Drug-Induced/ 146. exp Drug Toxicity/ 147. or/122-146 148. Coal Tar/ae [Adverse Effects] 149. Anthralin/ae [Adverse Effects] 150. Calcitriol/ae [Adverse Effects] 151. Acitretin/ae [Adverse Effects] 152. exp Cyclosporins/de, ae [Drug Effects, Adverse Effects] 153. Methotrexate/ae [Adverse Effects] 154. Tacrolimus/ae [Adverse Effects] 155. Dermatologic Agents/ae [Adverse Effects] 156. exp Adrenal Cortex Hormones/ae, de [Adverse Effects, Drug Effects] 157. exp Hydrocortisone/ae [Adverse Effects] 158. Beclomethasone/ae [Adverse Effects] 159. exp Betamethasone/ae [Adverse Effects] 160. Desoximetasone/ae [Adverse Effects] 161. Diucortolone/ae [Adverse Effects] 162. exp Fluocinolone Acetonide/ae [Adverse Effects] 163. Fluocortolone/ae [Adverse Effects] 164. Flurandrenolone/ae [Adverse Effects] 165. exp Triamcinolone/ae [Adverse Effects] 166. exp Steroids/ae [Adverse Effects] 167. or/148-166 168. 147 or 167 169. (psorias$ or psoriat$).tw. 170. exp psoriasis/
171. 172. 173. 174. 175. 176. 177. 178.
or/169-170 121 and 168 and 171 exp animals/ not (exp animals/ and humans/) 172 not 173 (comment or editorial).pt. 174 not 175 176 Limit 177 to yr=1990 - 2009
Appendix 11. EMBASE (OVID) search strategy (compliance)

EMBASE (OvidSP Online http://www.ovid.com/): 1980 to 2007 Week 49 1 compliance$.ti,ab. (46694) 2 complied.ti,ab. (1455) 3 compliance/ (1674) 4 comply.ti,ab. (3613) 5 (medicat$ adj4 adher$).ti,ab. (1732) 6 (drug$ adj4 adher$).ti,ab. (777) 7 (medicine$ adj4 adher$).ti,ab. (62) 8 (treatment adj4 adher$).ti,ab. (3072) 9 concordance$.ti,ab. (12825) 10 or/1-9 (68155) 11 psor$.ti,ab. (20549) 12 10 and 11 (171) 13 from 12 keep 1-171 (171)
Appendix 12. MEDLINE (OVID) search strategy (compliance)

MEDLINE(OvidSP Online http://www.ovid.com/): 1950 to November Week 2 2007 1. compliance$.ti,ab. (52891) 2. complied.ti,ab. (1748) 3. compliance/ (2982) 4. comply.ti,ab. (4307) 5. (medicat$ adj4 adher$).ti,ab. (2047) 6. (drug$ adj4 adher$).ti,ab. (878) 7. (medicine$ adj4 adher$).ti,ab. (76) 8. (treatment adj4 adher$).ti,ab. (3442) 9. concordance$.ti,ab. (14973) 10. or/1-9 (78297) 11. psor$.ti,ab. (25210) 12. 10 and 11 (162)
561
HISTORY
Protocol rst published: Issue 4, 2004 Review rst published: Issue 2, 2009
Date 15 December 2008 25 June 2008 29 September 2003
Event Amended Amended New citation required and conclusions have changed
Description Review amended to reect peer review comments Converted to new review format. Substantive amendment
CONTRIBUTIONS OF AUTHORS
The following contributions were made by the authors stated: Link with editorial base and coordinate contributions from co-authors (AM) Draft protocol (AM with contributions from MC, GD, GE, JM) Run searches (compliance) (AM) Identify relevant titles and abstracts from searches i.e. broad screen (AM, JM) Obtain copies of trials (AM) Select which trials to include (AM, JM and MC as arbitrator when necessary) Extract data from trials (AM, JM) Enter data into RevMan (AM) Carry out analysis (AM, JM) Interpret analysis (AM, JM) Draft nal review (AM with contribution from MC, GD, GE, JM) Update review (AM)
DECLARATIONS OF INTEREST
Anne Mason: In 2002/03, AM received funding of 11,500 from the American Pharmaceutical Group (APG) to assess the impact of additional resources on the NHS. The APG represents the ten leading US-owned pharmaceutical companies operating in the UK and includes Schering-Plough, the manufacturer of several topical corticosteroids. Mike Cork: none declared Gordon Dooley: none declared Gladys Edwards (Chief Executive of the Psoriasis Association): LeoPharma, Crookes Healthcare and Galderma are all corporate members of the Association. LeoPharma paid for GEs attendance and accommodation at the EADV Barcelona 2003. They have supported the Association with unrestricted grants for educational purposes.
GE has spoken at a roundtable discussion organised by Crookes Healthcare for which a payment was made to the Association.GE participated in a discussion organised by Galderma at the BAD conference in July 2004. Galderma gave the Association an unrestricted grant to support the development of the Associations web site. James Mason: In 1999/2000, JM received a grant from Crookes Healthcare for 19,500 to undertake research entitled: Psoriasis: a systematic review of the evidence for treatment.
SOURCES OF SUPPORT Internal sources

Funding from Centre for Reviews and Dissemination to update review (2002) for UK products only, UK. Award from University of York Fund for Staff on Fixed Term Contracts, UK.
External sources
Grant from Crookes Healthcare Ltd to do original systematic review (1999), UK.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

There are some differences between the protocol and the review. 1. In our protocol, we had stated our intention to adjust for the precision of ndings from within-patient studies for within-patient correlation. However, we were unsuccessful in our attempts to identify estimates of this correlation from published or unpublished sources. We therefore undertook sensitivity analysis to investigate differences between within-patient and between-patient studies. 2. In our protocol, we listed three primary outcome measures for data extraction. In the review, we also included the Patient Assessment of Global Improvement. 3. In our protocol, we stated that there would be no language restrictions when searching for publications. However, the search for longer-term studies of adverse events included a restriction to publications in English. 4. In our protocol, we stated our intention that studies meeting only some of the inclusion criteria stated above would be listed as excluded studies. However, as large numbers of studies would need to be listed, this was not feasible. Therefore, only those studies that were deemed potentially eligible for inclusion and for which full papers were retrieved, but which were subsequently found to fail to meet the inclusion criteria, were listed as excluded studies. 5. Throughout the text, all references to vitamin D3 have been replaced with vitamin D analogues 6. Under Types of studies, we relaxed the condition that studies were of at least 2 weeks duration . In the same section, we added the following sentence : If no useful effectiveness, withdrawal or adverse events data were available, either from the published paper or from sponsors or triallists, we excluded the study. 7. Under Types of interventions : we added the sentence The potency of topical corticosteroids was based on classications from a previous review (Mason 2002b). 8. Under Methods/ Selection of studies/ explanations of the studies excluded, we added the searches for studies exploring adverse events and compliance studies. 9. Under Methods/ Data extraction and management: we added the phrase between-patient design 10. Under Methods / Assessment of risk of bias in included studies/ d) , we removed the phrase in each arm. 11. Under Methods / Unit of analysis issues / Summarising primary outcomes with standardised mean differences we revised the text in this section to include the PAGI outcome and to provide a fuller explanation of our analytic approach. 12. Under Methods> Unit of analysis issues >Secondary outcomes: an explanation given because a different method of analysis used
13 Under Methods / Data collection and analysis/ sensitivity analysis, we have added text to describe the different types of sensitivity analysis undertaken. 14 We have replaced standardised weighted mean difference with standardised mean difference throughout the text to reect Cochrane terminology. 15. Under Methods / Data and Analyses / Subgroup analysis and investigation of heterogeneity we have inserted two paragraphs to explain our approach to statistical heterogeneity.
INDEX TERMS Medical Subject Headings (MeSH)

Administration, Topical; Adrenal Cortex Hormones [adverse effects; therapeutic use]; Bone Density Conservation Agents [adverse effects; therapeutic use]; Chronic Disease; Psoriasis [ drug therapy]; Randomized Controlled Trials as Topic; Vitamin D [adverse effects; analogs & derivatives; therapeutic use]
MeSH check words

Humans
564

Topical Treatments For Chronic Plaque Psoriasis (Review)

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Topical Treatments For Chronic Plaque Psoriasis (Review)

Uploaded by

Copyright:

Available Formats

Topical treatments for chronic plaque psoriasis (Review)

Mason AR, Mason J, Cork M, Dooley G, Edwards G

562 562 563 563 564

Topical treatments for chronic plaque psoriasis

Description of the condition

Description of the intervention

Why it is important to do this review

Criteria for considering studies for this review

Search methods for identication of studies

Results from the effectiveness RCT searches (2005)

Results from the effectiveness RCT update searches (2008)

Searching other resources

References from published studies and reviews

Data collection and analysis

Assessment of risk of bias in included studies

Assessment of methodological quality

Summarising primary outcomes with standardised mean differences

Figure 3. Placebo comparisons: data reported by outcome

Figure 4. Head-to-head comparisons: data reported by outcome

RESULTS Description of studies

Risk of bias in included studies

Baseline comparability of intervention and control groups

Method of generation of the randomisation sequence

(b) Total severity scores (TSS)

(d) Patient assessment of overall global improvement (PAGI)

(e) Combined endpoint (IAGI / TSS / PASI / PAGI)

Betamethasone 17-valerate 21 acetate plus tretinoin plus salicylic acid

(i) Findings from the main review

(e) Concordance or compliance with treatment

Summary of main results

Potential biases in the review process

Quality of the evidence

Agreements and disagreements with other studies or reviews

AUTHORS CONCLUSIONS Implications for practice

Implications for research

References to studies included in this review

References to studies excluded from this review

References to studies awaiting assessment

References to ongoing studies

Characteristics of included studies [ordered by study ID]

Authors judgement Unclear Yes

Description B - Unclear double-blind (patient / investigator)

not reported 0.0%

Baseline assessments? Baseline comparability demonstrated?

partial not reported

Notes Risk of bias Item

B - Unclear double-blind (patient / investigator)

No Yes Yes Yes

not reported 6.1%

Yes Yes Yes Yes

Barker 1999 (H)

Unclear Yes Yes Yes

not reported 13.3% partial partial

Barker 1999 (P)

Unclear Yes Yes Yes

not reported 10.0% partial partial

Authors judgement Unclear Unclear

Description B - Unclear double-blind (patient / investigator)

Unclear Yes Yes

not reported 4.0%

Bernhard 1991 (1)

Baseline comparability demonstrated?

Authors judgement Unclear Yes