lM SLCPLnCv ll8S1 MCSCCW S1A1L MLulCAL unlvL8Sl1?

____________
MLDICAL IACUL1
ulvlslon for lorelgn SLudenLs wlLh lnsLrucLlons ConducLed ln Lngllsh
______________

Department of Lconomy

Economy impact of asthma therapy


Laow ?ee kean
6
Lh
Course
Medlcal laculLy Lngllsh Medlum Croup 93


MCSCCW 2011
tudy Cb[ect|ve 1o compare asLhmarelaLed healLh care expendlLures among paLlenLs newly
prescrlbed fluLlcasone proplonaLe 44 or 110 g monLelukasL 3 or 10 mg or zaflrlukasL 20 mg

Des|gn 8eLrospecLlve cohorL analysls of medlcal and pharmacy clalms

ett|ng unlverslLyafflllaLed healLh ouLcomes research cenLer

at|ents Seven hundred elghLyone paLlenLs (aged 4 yrs) wlLh asLhma LreaLed wlLh
conLroller Lherapy for 9 monLhs (posLlndex perlod) wlLh no clalm for an lnhaled corLlcosLerold
or leukoLrlene modlfler ln Lhe prevlous 9 monLhs (prelndex perlod)
Intervent|on AsLhmarelaLed medlcal and pharmacy daLa from lnsurance clalms of four
managed care plans (Lwo norLheasLern one MldwesLern and one WesLern) were LabulaLed
over Lhe pre and posLlndex perlods

Measurements and Ma|n kesu|ts numbers of paLlenLs ldenLlfled were 284 beglnnlng
fluLlcasone proplonaLe 302 monLelukasL and 193 zaflrlukasL lluLlcasone proplonaLe
LreaLmenL was assoclaLed wlLh slgnlflcanLly (p0001) lower rlskad[usLed asLhmarelaLed
charges compared wlLh monLelukasL and zaflrlukasL LreaLmenL $328 $967 and $1339
respecLlvely ln Lhls cohorL fluLlcasone proplonaLe also was assoclaLed wlLh fewer
hosplLallzaLlons less need for addlLlonal conLroller agenLs and longer malnLenance on Lhe
lndex drug compared wlLh monLelukasL and zaflrlukasL
Conc|us|ons 8ased on Lhese realworld daLa as well as esLabllshed naLlonal and lnLernaLlonal
asLhma guldellnes conslderaLlon should be glven Lo lnhaled corLlcosLerold Lherapy parLlcularly
fluLlcasone proplonaLe for flrsLllne longLerm effecLlve managemenL of asLhma
Introduct|on
AsLhma ls a chronlc lnflammaLory dlsease wlLh lncreaslng prevalence and morbldlLy
1
CosLs for
asLhma care ln Lhe unlLed SLaLes are esLlmaLed aL $127 bllllon (1998 dollars) wlLh dlrecL
medlcal expendlLures accounLlng for 38
2
hyslclan servlces hosplLallzaLlon and emergency
deparLmenL cosLs consLlLuLe Lhe greaLesL percenLage (367) of Lhese dlrecL medlcal cosLs
CosLs for asLhmarelaLed emergency deparLmenL vlslLs and asLhmarelaLed hosplLallzaLlon are
subsLanLlal and should be consldered avoldable cosLs
3
1he Clobal lnlLlaLlve for AsLhma
4
and
Lhe naLlonal PearL Lung and 8lood lnsLlLuLe
3
have boLh proposed LhaL paLlenLs wlLh mlld
perslsLenL asLhma should recelve lnhaled corLlcosLerolds as flrsLllne LreaLmenL 1he guldellnes
of Lhe naLlonal PearL Lung and 8lood lnsLlLuLe propose leukoLrlene modlflers as an alLernaLlve
conLroller Lherapy
lnhaled corLlcosLerolds reduce Lhe morbldlLy and morLallLy of asLhma
610
Cur search of Lhe
llLeraLure however revealed no such evldence Lo esLabllsh LhaL leukoLrlene modlflers have a
slmllar beneflL ln paLlenLs wlLh asLhma ln addlLlon Lhe resulLs of recenL sLudles lndlcaLe LhaL
LreaLmenL of perslsLenL asLhma wlLh lnhaled corLlcosLerolds provldes slgnlflcanLly greaLer
lmprovemenL ln pulmonary funcLlon and asLhma sympLoms compared wlLh LreaLmenL wlLh
leukoLrlene modlflers
1114
1o deLermlne wheLher Lhe dlfferences observed beLween lnhaled
corLlcosLerolds and leukoLrlene modlflers ln randomlzed cllnlcal Lrlals are supporLed ln real
world cllnlcal pracLlce and lf so wheLher Lhese dlfferences LranslaLe lnLo slgnlflcanL cosL
savlngs for lnhaled corLlcosLerolds over leukoLrlene modlflers we compared asLhmarelaLed
healLh care expendlLures relaLed Lo lnhaled fluLlcasone proplonaLe (llovenL ClaxoSmlLhkllne
8esearch 1rlangle ark nC) wlLh LhaL of oral zaflrlukasL (AccolaLe AsLraZeneca harmaceuLlcals
WllmlngLon uL) and monLelukasL (Slngulalr Merck Co WesL olnL A) ln paLlenLs beglnnlng
conLroller Lherapy for asLhma
Data ource
We conducLed a reLrospecLlve cohorL sLudy of pharmacy and medlcal clalms from four
managed care plans of paLlenLs wlLh asLhma who recelved LreaLmenL wlLh fluLlcasone
proplonaLe 44 or 110 g monLelukasL 3 or 10 mg or zaflrlukasL 20 mg for a 9monLh perlod
uaLa for Lhls analysls were obLalned from lnsurance clalms records conslsLlng of llnked medlcal
and pharmacy daLa from four lndependenL pracLlce assoclaLlon model managed care plans (Lwo
norLheasLern reglon plans one MldwesLern reglon plan and one WesLern reglon plan)
conslsLlng of approxlmaLely 1 mllllon covered llves harmacy daLa were ldenLlfled by uslng Lhe
Amerlcan PosplLal lormulary Servlce code and Lhe naLlonal urug Code lncluded ln Lhe
pharmacy daLa were Lhe drug dlspensed daLe Lhe drug was dlspensed amounL charged and
amounL pald Medlcal clalms were ldenLlfled by uslng Lhe lnLernaLlonal ClasslflcaLlon of
ulseases nlnLh 8evlslon Cllnlcal ModlflcaLlon (lCu9CM) codes and CurrenL rocedural
1ermlnology lourLh 8evlslon codes lncluded ln Lhe medlcal clalms daLa were daLe of servlce
polnL of servlce amounL charged and amounL pald ln addlLlon daLa were avallable for daLe of
blrLh gender plan and plan ellglblllLy Llme for each paLlenL



Inc|us|on and Lxc|us|on Cr|ter|a
uaLa were lncluded ln Lhe analysls lf Lhe paLlenL had a prlmary lCu9CM code (493xxx) for
asLhma aL anyLlme ln Lhe daLabase 1lme of ellglblllLy was !uly 1 1997!une 30 1999 A LoLal of
104630 paLlenLs had Lhe code for asLhma 26933 paLlenLs ln Lhe Lwo norLheasL plans 21986
ln Lhe MldwesL plan and 33709 ln Lhe WesL plan 1he flrsL pharmacy clalms for fluLlcasone
proplonaLe 44 or 110 g monLelukasL 3 or 10 mg or zaflrlukasL 20 mg were deslgnaLed as Lhe
lndex daLe aLlenLs age had Lo be 4 years or older and enrollmenL ln Lhe plan had Lo be
conLlnuous for aL leasL 18 monLhs 9 monLhs before Lhe flrsL lndex prescrlpLlon (basellne
prelndex perlod) and 9 monLhs afLer (LreaLmenL posLlndex perlod) ldenLlfled paLlenLs could noL
have recelved an lnhaled corLlcosLerold or an oral leukoLrlene modlfler ln Lhe 9monLh basellne
prelndex perlod
uaLa were excluded from Lhe analysls lf Lhe paLlenL had pharmacy clalms for several drugs of
lnLeresL aL Lhe lndex daLe Lhe paLlenL was younger Lhan 4 years aL any Llme a dlagnosls was
made of cysLlc flbrosls (lCu9CM code 277) or chronlc obsLrucLlve pulmonary dlsease (lCu9
CM codes 491 492 4932 496) or Lhe paLlenL was older Lhan 43 years and had one or more
prescrlpLlons for lpraLroplum bromlde durlng Lhe sLudy perlod
Measures and Data Ana|ys|s
1he prlmary ouLcome was LoLal ad[usLed charges for asLhma care for each LreaLmenL group
durlng Lhe 9monLh LreaLmenL perlod afLer Lhe lndex daLe AsLhmarelaLed medlcal and
pharmacy paLlenL clalms daLa were LabulaLed over Lhe basellne and LreaLmenL perlods (9 mo
each) AsLhmarelaLed pharmacy clalms lncluded lnhaled and oral sLerolds lnhaled and oral
shorLacLlng
2
agonlsLs salmeLerol xanLhlne derlvaLlves and mlscellaneous anLllnflammaLory
agenLs (eg cromolyn sodlum) 1he medlcal clalms were ldenLlfled based on a llsLed dlagnosls
of asLhma and were caLegorlzed as physlclans offlce emergency deparLmenL ouLpaLlenL or
hosplLallzaLlon AsLhmarelaLed charges durlng Lhe 9monLh followup were compared among
Lhe fluLlcasone proplonaLe 44 and 110 g monLelukasL 3 and 10 mg and aflrlukasL 20 mg
groups
MulLlple llnear regresslon analysls was used Lo compare Lhe dlfferences ln posLlndex asLhma
care charges among Lhe Lhree drug groups ad[usLlng for dlfferences ln basellne demographlc
characLerlsLlcs asLhma care charges and uLlllzaLlon paLLerns varlables lncluded ln Lhe
regresslon model were age gender prelndex LreaLmenL wlLh oral sLerolds shorLacLlng
2

agonlsLs salmeLerol and Lheophylllne healLh plan and asLhmarelaLed prelndex charges
Charges were log Lransformed before lncluslon ln Lhe model owlng Lo hlghly skewed cosL daLa
seen wlLh admlnlsLraLlve clalms Ad[usLed mean charges were calculaLed by uslng leasL squares
mean and a reLransformaLlon meLhod (le smearlng Lechnlque)
13

A loglsLlc regresslon model was used Lo assess Lhe relaLlonshlp beLween drug group and
hosplLallzaLlons and emergency deparLmenL vlslLs durlng Lhe followup perlod 1he same
varlables used ln Lhe cosL model were used ln Lhe loglsLlc regresslon model excepL for number
of hosplLallzaLlons or emergency deparLmenL vlslLs ln Lhe prelndex perlod whlch were lncluded
as varlables only ln Lhelr respecLlve models Ad[usLed odds raLlos for an asLhmarelaLed
hosplLallzaLlon or emergency deparLmenL vlslL were generaLed from Lhe loglsLlc regresslon
model wlLh fluLlcasone proplonaLe as Lhe referenL group
1he sLudy sample was anLlclpaLed Lo be adequaLe for deLecLlon of dlfferences ln asLhma care
charges buL noL large enough Lo deLecL dlfferences ln resource uLlllzaLlons All sLaLlsLlcal
analyses were performed aL an a level of 003 and 8onferronl ad[usLmenL was made for
mulLlple comparlsons
A senslLlvlLy analysls was performed Lo enhance Lhe generallzablllLy of Lhe daLa Lo varlous age
groups Subgroups were examlned Lo deLermlne lf Lhe dlfferences ln overall asLhma care
charges were observed ln Lhese cohorLs lndlvldually 1he daLa were grouped lnLo Lwo
subgroups for comparlson aged 12 years or older and aged 411 years
llnally kaplanMeler survlval analysls was performed Lo deLermlne Lhe Llme Lo addlLlonal
Lherapy among Lhe Lhree LreaLmenL groups
kesu|ts
1able 1 summarlzes Lhe demographlcs of each LreaLmenL cohorL uaLa for 781 sub[ecLs were
lncluded ln Lhe analysls 284 paLlenLs were Laklng fluLlcasone proplonaLe 302 paLlenLs
monLelukasL and 193 paLlenLs zaflrlukasL 1he sub[ecLs mean age was 31 years 430 (33)
were women and 331 (43) were men 1he numbers of paLlenLs ln Lhe age 12 years or older
subgroup and Lhe age 411 years subgroup for each drug cohorL were respecLlvely fluLlcasone
proplonaLe 242 and 42 paLlenLs monLelukasL 238 and 44 and zaflrlukasL 191 and 4 Cwlng Lo
Lhe lnadequaLe sample ln Lhe age 411 years subgroup of Lhe zaflrlukasL cohorL lL was noL
lncluded ln Lhe analysls of Lhls subgroup
Un|var|ate Ana|ys|s
Across all Lhree cohorLs no dlfference was noLed ln prelndex LreaLmenL wlLh shorLacLlng
2

agonlsLs or salmeLerol Powever a slgnlflcanL dlfference was noLed ln prelndex LreaLmenL wlLh
oral sLerolds (p003) Speclflcally 23 (81) of Lhe 284 paLlenLs ln Lhe fluLlcasone proplonaLe
group had aL leasL one pharmacy clalm for an oral sLerold ln Lhe prelndex perlod whereas 69
(228) of Lhe 302 paLlenLs ln Lhe monLelukasL group and 41 (210) of Lhe 193 paLlenLs ln Lhe
zaflrlukasL group had aL leasL one clalm no slgnlflcanL dlfferences were noLed ln Lhe
percenLages of paLlenLs wlLh hosplLallzaLlons or emergency deparLmenL vlslLs ln Lhe prelndex
perlod however paLlenLs Laklng zaflrlukasL had more asLhmarelaLed evenLs compared wlLh
paLlenLs ln Lhe fluLlcasone proplonaLe and monLelukasL groups ln Lhe prelndex perlod ln
addlLlon no slgnlflcanL dlfference was observed ln Lhe prelndex mean LoLal asLhma charges
whlch ls reflecLed ln Lhe prelndex medlan charges of $90 for Lhe fluLlcasone proplonaLe group
$120 for Lhe monLelukasL group and $118 for Lhe zaflrlukasL group Powever Lhe mean
charges were numerlcally much hlgher ln Lhe zaflrlukasL group Lhan ln Lhe fluLlcasone
proplonaLe and monLelukasL groups (1able 1)
unad[usLed LoLal cosL for asLhma care ln Lhe posLlndex perlod for Lhe fluLlcasone proplonaLe
group was $376 1he charges for Lhe monLelukasL and zaflrlukasL groups were hlgher Lhan Lhose
for Lhe fluLlcasone proplonaLe group wlLh unad[usLed LoLal charges of $902 and $1417
respecLlvely unad[usLed and ad[usLed charges wlLh correspondlng 93 confldence lnLervals
(Cls) are reporLed ln 1able 2 1he changes ln pre and posLlndex mean charges for asLhma care
showed a slmllar Lrend wlLh Lhe fluLlcasone proplonaLe group havlng Lhe lowesL change an
lncrease of $131 whereas Lhe monLelukasL and zaflrlukasL groups showed lncreases of $347
and $379 respecLlvely ln addlLlon Lhe percenLage of paLlenLs wlLh aL leasL one hosplLallzaLlon
ln Lhe posLlndex perlod decllned 438 for Lhe fluLlcasone proplonaLe group buL lncreased 763
for Lhe monLelukasL group and lncreased 8 for Lhe zaflrlukasL group (1able 3) lurLhermore
paLlenLs experlenclng aL leasL one asLhmarelaLed emergency deparLmenL vlslL decllned 86
for paLlenLs sLarLlng fluLlcasone proplonaLe and lncreased 304 for paLlenLs sLarLlng
monLelukasL and 363 for paLlenLs sLarLlng zaflrlukasL 1he mean number of occurrences of
dlspenslng Lhe lndex drug ln Lhe posLlndex perlod for Lhe Lhree groups also dlffered aLlenLs ln
Lhe fluLlcasone proplonaLe group had slgnlflcanLly fewer (p0001) lndex drugdlspenslng
occurrences (27) Lhan Lhose of Lhe monLelukasL (42) and zaflrlukasL (40) groups over Lhe 9
monLh LreaLmenL perlod
Mu||tvar|ate Ana|ys|s
MulLlple llnear regresslon analysls showed LhaL fluLlcasone proplonaLe 44 and 110 g was
assoclaLed wlLh slgnlflcanLly lower asLhma care charges compared wlLh Lhose of monLelukasL 3
and 10 mg (p001) and zaflrlukasL (p0001) durlng Lhe 9monLh posLlndex perlod (1able 2)
lluLlcasone proplonaLe was observed Lo have an ad[usLed mean LoLal cosL for asLhma care of
$328 for Lhe 9monLh LreaLmenL perlod whereas monLelukasL and zaflrlukasL had ad[usLed
mean LoLal charges of $967 and $1339 respecLlvely Slmllar dlfferences were observed ln Lhe
age 12 years or older subgroup aLlenLs Laklng fluLlcasone proplonaLe had slgnlflcanLly lower
(p0001) ad[usLed mean posLlndex charges/ paLlenL ($336) compared wlLh Lhose charges for
paLlenLs Laklng monLelukasL ($961) and Lhose Laklng zaflrlukasL ($1391) SlgnlflcanLly lower
mean LoLal asLhma care charges also were observed for fluLlcasone proplonaLe ($423) Lhan for
monLelukasL ($932) ln Lhe age 411 years subgroup (p00001)
LoglsLlc regresslon analysls lndlcaLed LhaL paLlenLs LreaLed wlLh zaflrlukasL had a 34fold (93
Cl 11107) greaLer rlsk of an asLhmarelaLed hosplLallzaLlon compared wlLh Lhose Laklng
fluLlcasone proplonaLe whereas paLlenLs Laklng monLelukasL had a 19fold (93 Cl 0662)
lncrease ln rlsk compared wlLh Lhose LreaLed wlLh fluLlcasone proplonaLe ln Lhe age 12 years or
older subgroup paLlenLs LreaLed wlLh zaflrlukasL had a 37fold (93 Cl 11130) lncrease ln Lhe
rlsk of a hosplLallzaLlon compared wlLh Lhose Laklng fluLlcasone proplonaLe whereas paLlenLs
LreaLed wlLh monLelukasL had a 22fold (93 Cl 0684) lncrease compared wlLh paLlenLs
Laklng fluLlcasone proplonaLe Compared wlLh Lhe fluLlcasone proplonaLe group paLlenLs
recelvlng zaflrlukasL had a 18fold (93 Cl 0749) lncrease ln Lhe rlsk of an asLhmarelaLed
emergency deparLmenL vlslL whereas paLlenLs recelvlng monLelukasL had a 09fold (93 Cl
0326) decrease ln Lhls rlsk ln Lhe age 12 years or older subgroup paLlenLs Laklng zaflrlukasL
had a 26fold (93 Cl 0977) lncrease ln Lhe rlsk of an asLhmarelaLed emergency deparLmenL
vlslL and paLlenLs Laklng monLelukasL had a 16fold (93 Cl 0330) lncrease ln Lhls rlsk noL
enough hosplLallzaLlons or emergency deparLmenL vlslLs occurred ln Lhe age 411 years
subgroup Lo perform a loglsLlc regresslon
1he need Lo swlLch Lo or add anoLher lnhaled corLlcosLerold or leukoLrlene modlfler was more
pronounced for Lhe monLelukasL and zaflrlukasL groups Lhan for Lhe paLlenLs sLarLlng
fluLlcasone proplonaLe SlgnlflcanLly (p0001) fewer paLlenLs ln Lhe fluLlcasone proplonaLe
group (21/284 74) swlLched or added Lherapy compared wlLh paLlenLs ln Lhe monLelukasL
(93/302 313) or zaflrlukasL (83/193 426) groups 1he ad[usLed rlsk of swlLchlng Lo or
addlng anoLher conLroller agenL was 72 Llmes hlgher for Lhe zaflrlukasL group (p0001) and 49
Llmes hlgher for Lhe monLelukasL group (p0001) compared wlLh Lhe fluLlcasone proplonaLe
group ln addlLlon kaplanMeler survlval analysls revealed LhaL paLlenLs LreaLed wlLh
monLelukasL and Lhose LreaLed wlLh zaflrlukasL were more llkely Lo recelve addlLlonal conLroller
LreaLmenL sooner Lhan Lhe paLlenLs Laklng fluLlcasone proplonaLe (p00001 llgure 1) We also
observed LhaL paLlenLs recelvlng addlLlonal asLhma Lherapy oLher Lhan Lhelr lndex LreaLmenL
had slgnlflcanLly hlgher asLhma care charges Lhan Lhose of paLlenLs who dld noL have clalms for
oLher conLroller drugs (p001 daLa noL shown)

I|gure 1
kaplanMeler survlval curve lndlcaLes Lhe percenLage of paLlenLs conLlnulng Lo recelve only
Lhe lndex drug over Lhe 9monLh LreaLmenL perlod aLlenLs recelvlng monLelukasL (MCn)
and Lhose recelvlng zaflrlukasL (ZAl) were more llkely Lo recelve addlLlonal conLroller
LreaLmenL sooner Lhan Lhe paLlenLs ln Lhe fluLlcasone proplonaLe (l) group (p00001)





D|scuss|on
ln Lhls sLudy LreaLmenL wlLh Lhe lnhaled corLlcosLerold fluLlcasone proplonaLe 44 and 110 g ln
paLlenLs wlLh asLhma who were noL prevlously recelvlng elLher an lnhaled corLlcosLerold or
leukoLrlene modlfler was less cosLly Lhan LreaLmenL wlLh a leukoLrlene modlfler monLelukasL or
zaflrlukasL Cur resulLs supporL Lhe concluslons of recenL cllnlcal Lrlals LhaL demonsLraLe Lhe
advanLages of lnhaled corLlcosLerolds compared wlLh monLelukasL and zaflrlukasL ln lnhaled
corLlcosLeroldnaive paLlenLs
1113
ln addlLlon reducLlons ln emergency deparLmenL vlslLs and
hosplLallzaLlon evenLs seen ln paLlenLs recelvlng fluLlcasone proplonaLe 44 and 110 g occurred
desplLe Lhe lower number of mean prescrlpLlon clalms for Lhe fluLlcasone proplonaLe group
compared wlLh Lhe monLelukasL and zaflrlukasL groups
1hls cllnlcal raLlonale supporLlng lnhaled corLlcosLerolds as Lhe flrsLllne LreaLmenL for
perslsLenL asLhma has been valldaLed ln several randomlzed cllnlcal Lrlals ln one
sLudy
11
greaLer lmprovemenL ln lung funcLlon was demonsLraLed wlLh fluLlcasone proplonaLe
44 g (Lwo puffs Lwlce/day) compared wlLh zaflrlukasL 20 mg Lwlce/day ln addlLlon beLLer
lmprovemenL was shown wlLh fluLlcasone proplonaLe 44 g compared wlLh zaflrlukasL ln mosL
of Lhe secondary efflcacy parameLers (mornlng and evenlng peak flow and asLhma
sympLoms)
11
ln anoLher slmllar sLudy
13
Lhe auLhors compared fluLlcasone proplonaLe 44 g
Lwo puffs Lwlce/day wlLh monLelukasL 10 mg once/day ln paLlenLs who prevlously were
recelvlng a shorLacLlng
2
agonlsL alone ln Lhls 24week sLudy superlor lmprovemenL was
shown ln all ouLcome parameLers (lung funcLlon lmprovemenL and sympLoms) for fluLlcasone
proplonaLe compared wlLh monLelukasL
lnhaled corLlcosLerolds may lower Lhe overall morbldlLy of asLhma by reduclng Lhe rlsk of an
asLhmarelaLed hosplLallzaLlon as well as by reduclng asLhmarelaLed emergency deparLmenL
vlslLs 1he auLhors of one sLudy
8
assessed Lhe relaLlve rlsk of hosplLallzaLlon for paLlenLs
accordlng Lo shorLacLlng
2
agonlsL and lnhaled corLlcosLerold LreaLmenL AfLer ad[usLlng for
LreaLmenL wlLh a shorLacLlng
2
agonlsL LreaLmenL wlLh an lnhaled corLlcosLerold was
assoclaLed wlLh a 30 reducLlon ln Lhe rlsk of an asLhmarelaLed hosplLallzaLlon relaLlve Lo Lhe
rlsk ln paLlenLs who were recelvlng only a shorLacLlng
2
agonlsL lncreases ln Lhe use and Lhe
amounL of lnhaled corLlcosLerolds over Lhe lasL several years have been assoclaLed wlLh a
reducLlon ln asLhmarelaLed emergency deparLmenL vlslLs and asLhmarelaLed
hosplLallzaLlons
6
Cur analysls shows LhaL LreaLmenL wlLh fluLlcasone proplonaLe was
assoclaLed wlLh a lower rlsk of an asLhmarelaLed hosplLallzaLlon or emergency deparLmenL vlslL
Lhan LhaL wlLh monLelukasL and zaflrlukasL LreaLmenL
ln addlLlon Lo Lhe beneflLs of lnhaled corLlcosLerolds on reduclng asLhmarelaLed healLh care
resources beneflLs on asLhma morLallLy have been noLed 1he auLhors of a recenL
sLudy
7
concluded LhaL paLlenLs who regularly Lake lowdose lnhaled corLlcosLerolds decrease
Lhelr rlsk of an asLhmarelaLed deaLh by 21 for each canlsLer consumed ln a year 1o our
knowledge no publlshed sLudy Lo daLe llnks leukoLrlene modlflers Lo reducLlons ln emergency
deparLmenL vlslLs hosplLallzaLlons cosLs or morLallLy lurLhermore conslderlng LhaL faLal
asLhma has been reporLed Lo occur ln 30 of paLlenLs prevlously LhoughL Lo have mlld asLhma
lnhaled corLlcosLerolds may have an advanLage over leukoLrlene modlflers ln Lhese paLlenLs
16

ln our analysls daLa were classlfled accordlng Lo Lhe paLlenLs lnlLlal drug All consequences of
lnlLlal LreaLmenL selecLlon swlLches or augmenLaLlons were regarded as common and
lmporLanL consequences of lnlLlal LreaLmenL selecLlon SwlLchlng Lo or augmenLaLlon wlLh
anoLher conLroller agenL could be a proxy for asLhma conLrol Lxcludlng Lhe ouLcomes of Lhose
paLlenLs whose Lherapy was augmenLed would have blased Lhe resulLs because only Lhe
healLhlesL sub[ecLs would have remalned for Lhe Lhree groups ln our sLudy slgnlflcanLly more
paLlenLs LreaLed wlLh monLelukasL or zaflrlukasL swlLched or augmenLed Lhelr Lherapy wlLh
anoLher leukoLrlene modlfler or lnhaled corLlcosLerold compared wlLh paLlenLs LreaLed wlLh
fluLlcasone proplonaLe
AlLhough resulLs from cllnlcal Lrlals have hlgh levels of lnLernal valldlLy and are Lhe crlLerlon
sLandard ln deLermlnlng dlfferences ln efflcacy Lhey have weak generallzablllLy Lo realworld
seLLlngs Cllnlcal Lrlals are performed under ldeal seLLlngs and dlfferences ln prescrlblng
paLLerns formularles healLh plans and paLlenL varlables such as compllance are noL a facLor ln
Lhe ouLcomes of lnLeresL 8eLrospecLlve cohorL sLudles such as our analysls LhaL use pharmacy
and medlcal clalms can enhance and supporL randomlzed cllnlcal Lrlals
1721
1hese sLudles are
lnLended Lo complemenL Lhe efflcacy daLa from cllnlcal sLudles wlLh cosL and effecLlveness daLa
generaLed from rouLlne cllnlcal pracLlce 1he sLrengLh of Lhese cohorL sLudles ls Lhe enhanced
generallzablllLy Lo cllnlcal pracLlce and healLh care payers 8eLrospecLlve cohorL sLudles creaLe
comparlson populaLlons by employlng lncluslon and excluslon crlLerla for Lhe paLlenLs Lake lnLo
conslderaLlon comorbldlLles allow for analysls of larger populaLlons and follow up groups for
longer perlods of Llme Lhan would be avallable ln Lyplcal cllnlcal Lrlals lurLhermore because
Lhese daLa are noL sub[ecL Lo Lhe conLrolled envlronmenL of a cllnlcal Lrlal Lhey may beLLer
reflecL acLual condlLlons of cllnlcal pracLlce or Lhe real world 1herefore reLrospecLlve analyses
of clalms daLa have been deLermlned Lo be sulLable for conducLlng comparlsons of healLh care
uLlllzaLlon and cosLs under realworld condlLlons
1721
Slnce Lhls analysls was based on daLa
from a realworld seLLlng (four managed care plans) Lhe flndlngs may be more generallzable Lo
physlclans payers and paLlenLs because Lhe ouLcomes LhaL are observed may be affecLed by
varlables experlenced ln cllnlcal pracLlce
As wlLh any sLudy llmlLaLlons musL be recognlzed 1hls sLudy compared Lhree LreaLmenLs over a
9monLh perlod Slnce monLelukasL was noL avallable unLll Lhe flrsL quarLer of 1998 a 9monLh
followup was Lhe longesL LhaL could be obLalned We were able Lo gaLher lnformaLlon only
unLll !une 30 1999 Pence Lhe observed dlfferenLlals ln resource uLlllzaLlon cannoL be easlly
exLrapolaLed beyond Lhe 9 monLhs afLer lnlLlaLlon of Lherapy Slnce Lhe cohorLs were ldenLlfled
over a 12monLh perlod asLhma exacerbaLlons due Lo dlfferlng seasons should noL be a
llmlLaLlon Powever furLher sLudles wlLh longer followup perlods are recommended ln
addlLlon Lhe daLa used for Lhls analysls were clalms daLa from managed care populaLlons
1herefore Lhe flndlngs may noL be generallzable Lo oLher populaLlons or seLLlngs Also paLlenLs
were ldenLlfled accordlng Lo an lCu9CM code (493xxx) for asLhma and Lhe presence of a
pharmacy clalm for Lhe drugs of lnLeresL 1hls meLhod may lead Lo mlsclasslflcaLlon of Lhe
dlsease especlally ln chlldren Powever mlsclasslflcaLlon ls probably nondlfferenLlal Lhus Lhe
suspecLed dlfferences among Lhe groups should noL have affecLed Lhe ouLcomes of lnLeresL
lurLhermore Lhe small sample and relaLlve rareness of hosplLallzaLlons may explaln why a
sLaLlsLlcally slgnlflcanL dlfference was noL observed ln asLhmarelaLed hosplLallzaLlon for
monLelukasL versus fluLlcasone proplonaLe ln Lhls sLudy even Lhough Lhe ad[usLed odds raLlo
was 19
Some dlfflculLy exlsLs ln ldenLlfylng comparable LreaLmenL groups wlLh clalms analysls slnce Lhe
cohorLs are noL randomlzed 1hus lnLernal valldlLy of Lhe sLudy ls llmlLed Comparlson of raw
daLa beLween Lhe cohorLs ls of llmlLed value ln deLecLlng assoclaLlons beLween Lherapy and
posLlndex cosL of care ln addlLlon unlvarlaLe analyses are lncapable of Laklng lnLo accounL
basellne dlfferences beLween Lwo cohorLs 1herefore lL could be argued LhaL any observed
dlfferences ln asLhmaspeclflc cosLs could be due Lo confoundlng varlables whlch dlffer
beLween Lhe cohorLs and are Lhe Lrue cause of Lhe dlfferences ln cosL Confoundlng can be
mlnlmlzed Lhrough proper analysls buL lL cannoL be easlly conLrolled ln Lhe deslgn of an
observaLlonal sLudy Cne such meLhod ls mulLlvarlaLe analysls uslng mulLlple llnear regresslon
analysls on logLransformed charges ad[usLlng for observed dlfferences such as age and
prelndex charges showed LhaL fluLlcasone proplonaLe Lherapy was assoclaLed wlLh lower
LreaLmenL charges compared wlLh Lhose of monLelukasL and zaflrlukasL 1hls assoclaLlon was
observed conslsLenLly ln Lhe analysls of sub[ecLs aged 411 years and ln Lhose aged 12 years or
older who recelved fluLlcasone proplonaLe Powever as wlLh mosL observaLlonal sLudy deslgns
Lhe assoclaLlons observed may noL be fully explalned by Lhe regresslon model unobserved
varlables could noL be accounLed for ln Lhls sLudy deslgn and poLenLlally Lhose unobserved
varlables could be assoclaLed wlLh Lhe ouLcome as well ln addlLlon oLher meLhods such as Lhe
use of lnsLrumenLal varlables and propenslLy scores have been recommended Lo mlnlmlze
confoundlng
2223
ropenslLy scores have Lhe same llmlLaLlons as regresslon because Lhey can
Lake lnLo accounL only observable varlables Whereas lnsLrumenLal varlables have Lhe ablllLy Lo
accounL for unobservable varlables developmenL of an approprlaLe lnsLrumenL ls exceedlngly
dlfflculL Clven Lhls llmlLaLlon of reLrospecLlve cohorL sLudles Lhe resulLs of our analysls musL be
valldaLed wlLh a randomlzed prospecLlve sLudy
1he concluslon of Lhe naLlonal and lnLernaLlonal asLhma guldellnes whlch recommend
LreaLmenL wlLh lnhaled corLlcosLerolds as Lhe flrsLllne conLroller Lherapy for asLhma
43
ls
supporLed by randomlzed cllnlcal Lrlals Powever desplLe a greaLer number of refllls observed
wlLh monLelukasL and zaflrlukasL fluLlcasone proplonaLe demonsLraLed greaLer efflcacy relaLlve
Lo Lhese leukoLrlene modlflers ln our analysls whlch used realworld clalms daLa CosL savlngs
assoclaLed wlLh lower resource uLlllzaLlon comblned wlLh Lhe lower cosL of concomlLanL drugs
seen ln Lhe fluLlcasone proplonaLe group supporL Lhe recommendaLlon for LreaLmenL wlLh an
lnhaled corLlcosLerold over a leukoLrlene modlfler as Lhe flrsLllne conLroller agenL for asLhma
1he need for realworld ouLcomes daLa ln documenLlng whaL works ln paLlenL care ls
lncreaslngly lmporLanL CuLcomes analysls should lead Lo beLLer use of resources slnce one of
Lhe goals of asLhma managemenL ls Lo help reduce cosL
3
Compared wlLh lnlLlaLlon of
monLelukasL or zaflrlukasL Lherapy ln paLlenLs noL prevlously Laklng elLher an lnhaled
corLlcosLerold or a leukoLrlene modlfler Lhe lnlLlaLlon of Lherapy wlLh fluLlcasone proplonaLe
an lnhaled corLlcosLerold was assoclaLed wlLh lower asLhmarelaLed medlcal charges over a 9
monLh perlod even afLer ad[usLlng for Lhe basellne dlfferences beLween Lhe groups
aLlenLs recelvlng fluLlcasone proplonaLe had lower overall asLhmarelaLed charges fewer
hosplLallzaLlons less need for addlLlonal conLroller agenLs and longer malnLenance of Lhelr
lnlLlal Lherapy compared wlLh paLlenLs recelvlng monLelukasL or zaflrlukasL All of Lhe
aforemenLloned parameLers may be vlewed as proxy measures of efflcacy 1hese resulLs from a
realworld seLLlng coupled wlLh Lhe naLlonal lnsLlLuLes of PealLh guldellnes Lhe sclenLlflc
raLlonale supporLlng lnhaled corLlcosLerolds as an anLllnflammaLory and daLa from several
randomlzed cllnlcal Lrlals suggesL LhaL sLrong conslderaLlon be glven Lo Lherapy wlLh an lnhaled
corLlcosLerold ln parLlcular fluLlcasone proplonaLe as a flrsLllne longLerm conLrol agenL for
effecLlve asLhma managemenL