The New Insight of Nociceptive Pain

Management: Focus on Safety &

Efficacy
DR. Dr. Blondina Marpaung SpPD-KR

Mechanism Based
Physiologic /
nociceptive1
Pain arising from
activation of nociceptors

Inflammatory2
Pain caused by injury to
body tissues
(musculoskeletal,
cutaneous or visceral)

1.
2.
3.

Example:
Example:
Peripheral
- Pinched
- Fibromyalgia
Mixed
- Stung by mosquito
- Irritable bowel syndrome
Common
descriptors:
Pain
with inflammatory and
Common
Similar to
inflammatory
paindescriptors
Neuropathic
components
Similar to neuropathic pain
Example:
Peripheral
Example:
Example:
- Postherpetic neuralgia
- Low
pain with radiculopathy
- Pain
dueback
to- inflammation
Trigeminal
neuralgia
- Cervical
radiculopathy
- Limb
pain after
a
fracture
- Diabetic peripheral neuropathy
- Cancer
- Joint
pain in-pain
osteoarthritis
Postsurgical neuropathy
Carpal
tunnel
syndrome
- Postoperative visceral
pain
- Posttraumatic
neuropathy
Central
Common descriptors:
- Poststroke pain
Aching
Common descriptors
Sharp
Burning
Throbbing
Tingling
Hypersensitivity to touch or cold

Psychogenic
(functional)3
Pain due to abnormal
responsiveness or function
of the nervous system
without neurologic deficit
or peripheral abnormality

Neuropathic1
Pain arising as a direct
consequence of a lesion or
disease affecting the
somatosensory system

Loeser JD, Treede RD. The Kyoto Protocol of IASP Basic Pain Terminology. Pain 2008;137:473-477.
Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57.
Woolf CJ. Pain: Moving from Symptom Control toward Mechanism-Specific Pharmacologic Management.. Ann Intern Med 2004;140:441-451

RHEUMATIC PAIN MANAGEMENT

Education
Non pharmacologic : diet, exercise, rehabilitation
Pharmacologic :
NSAIDs
DMARD :
Conventional
Biologic
Glucocorticoid

Surgery
Others

NSAIDs
The NSAIDs/Coxib are used to modify the symptoms of RA.
The use of NSAIDs is recommended at disease onset, when
a new DMARD is introduced, and occasionally when
uncontrolled isolated symptoms persist despite good
response to a DMARD.
The need for continuous use of NSAIDs in a patient with RA
should be interpreted as inadequate control of inflammatory
activity and should, therefore, lead to reassessment of the
DMARD regimen.

NSAIDs
All NSAIDs should be used at the full dose for
at least 1 week before considering the
treatment to have failed. Once symptoms have
been controlled, the minimum effective dose
should be used.
There is no evidence that some NSAIDs are
better than others, but vary in their potential
gastrointestinal, liver and cardio-renal toxicity;
therefore, when choosing the agent and dose,
healthcare professionals should take into
account individual patient risk factors

The Role of COX-2 Inhibitors

(COXIBs)
in Inflammatory Pain

Role of COX-2 in Pain

Peripheral

Central

Trauma/inflammation

Interleukin-1

Release of arachidonic acid

COX-2
Prostaglandins in periphery

Expression of COX-2
Prostaglandins in spinal cord

Sensitivity of peripheral
nociceptors
(primary hyperalgesia)

Central sensitization
Abnormal pain sensitivity

Pain
Baba H et al. J Neurosci. 2001;21:1750-6.
Ek M et al. Nature. 2000;410:430-1.
Samad TA et al. Nature. 2001;410:471-5.

Arachidonic Acid Cascade

& COX Hypothesis
Arachidonic Acid
Cyclooxygenase (COX)

COX-1

X
Body Homeostasis
Gastric integrity
Renal function
Platelet function

COX-2
Nonselective
NSAID

X
X

COX-2
selective
Inhibitor

Inflammation
Pain

Needleman P. et al. J Rheumatol 1997;24(suppl 49):6-8

Fitzgerald GA et al. N Engl J Med 2001;345:433-42

COX-1 vs COX-2
COX-1

COX-2

Constitutive

Inducible (in most tissues)

Present in most tissues

Induced mainly at sites of

inflammation by cytokines

Synthesizes PGs that

regulate physiologic
processes
Especially important in
gastric mucosa
kidneys
platelets
vascular endothelium
Needleman P et al. J Rheumatol. 1997;24(suppl 49):6-8.
Dubois RN et al. FASEB J. 1998;12:1063-73.

Synthesizes PGs that mediate

inflammation, pain, and fever
Constitutive expression
primarily in
brain
kidneys

CELECOXIB:
Efficacy in Chronic Diseases

CELECOXIB vs. diclofenac:

6-week Knee OA Trial
McKenna et al. 2001: Patients Assessment of Pain

Mean Change (mm)

Less Pain

Patients Assessment of Pain (VAS): Mean change

at week 6
*p=0.001 vs. placebo

placebo
(n=200)
VAS=visual analogue scale.
McKenna F et al. Scand J Rheumatol 2001;30:1118.

celecoxib
100 mg BID
(n=199)

diclofenac
50 mg TID
(n=199)

CELECOXIB vs. diclofenac:

6-week Knee OA Trial
McKenna et al. 2001: American Pain Society Pain Measure
American Pain Society (APS) Pain Measure:
Worst Pain in the Past 24 Hours
Baseline

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Mean Change in Score

Less Pain

0.0
-0.5

p=0.05, active treatment vs.

placebo (days 1-7).

-1.0
-1.5
-2.0
-2.5
-3.0

placebo (n=200)
-3.5
-4.0

celecoxib 100 mg BID (n=199)

diclofenac 50 mg TID (n=199)

McKenna F et al. Scand J Rheumatol. 2001;30:11-18.

CELECOXIB vs. diclofenac:

24-week RA Trial
Emery et al. 1999: Number of Tender/Painful Joints

Number of tender/painful joints

Mean reduction in number of tender/painful joints

*p<0.012 vs. diclofenac

Celecoxib 200 mg BID (n=326)

Diclofenac SR 75 mg BID (n=329)

Week
Emery P et al. Lancet 1999;354:2106-2111.

CELECOXIB vs. diclofenac:

12-week AS Trial

VAS Score (mm)

Sieper et al. 2008: Improvement in VAS Pain Scores

Baseline

week 12

celecoxib
200 mg BID
(n=153)

Baseline

week 12

celecoxib
200 mg OD
(n=150)

Baseline

week 12

diclofenac SR
75 mg BID
(n=155)

VAS=visual analogue scale.

Data are mean values (SD). Least squares mean treatment contrasts (95% confidence intervals): celecoxib 200 mg od 2.9
(2.7; 95% CI 2.4 to 8.2); celecoxib 200 mg BID 2.1 (2.8; 95% CI 3.3 to 7.6); diclofenac values not reported.
No p-values reported.
Sieper J et al. Ann Rheum Dis 2008;67:323329.

CELECOXIB:
Other indications approved by
US FDA

THE ONLY COXIB APPROVED BY US FDA!

09/25/09

US FDA APPROVAL
for Celecoxib on Acute Pain

09/25/09
http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020998s018,019lbl.pdf

CELECOXIB: Post-Oral Surgery

Cheung et al. 2007: Onset of Action
Median time to onset of action
Min

24

Min

Hour

26

28

30

32

>2
4

pl
ac
e

bo

(n
=5
7)

Min

ce
40 leco
0
m xib
g
(n
=5
7)

Min

ib
u
40 pro
0
m fen
g
(n
=5
7)

Min

p=0.05 vs. placebo.

Cheung R et al. Clin Ther 2007;29 Suppl:2498-2510.

CELECOXIB: Post-Oral Surgery

Cheung et al. 2007: Time to Rescue Medication

Min

10
0

Min

Hour

11
1

50
0

60
0

63
8

>2
4

ce
40 leco
0
m xib
g
(n
=5

ib
u
40 pro
0
m fen
g
(n
=5

eb
o
pl
ac

7)

Min

7)

Min

(n
=5
7)

Min

p=0.05 vs. placebo.

p=0.05 vs. ibuprofen.

Cheung R et al. Clin Ther 2007;29 Suppl:2498-2510.

CELECOXIB vs. morphine:

Knee Arthroscopy Surgery
Huang et al. 2008: Resting Pain Scores
Resting pain following knee arthroplasty
* p<0.05 vs. morphine alone.

Mean VAS Pain Score (mm)

morphine (n=40)
celecoxib 200 mg BID + morphine (n=40)

Post-operative time
VAS=visual analogue scale.
Huang YM et al. BMC Musculoskelet Disord 2008;9:77.

CELECOXIB vs. morphine:

Knee Arthroscopy Surgery
Huang et al. 2008: Morphine Consumption

Mean PCA Morphine (mg)

* p<0.05 vs. morphine alone.

6hr

12hr

morphine (n=40)
celecoxib + morphine (n=40)

PCA=patient-controlled analgesic morphine.

Huang YM et al. BMC Musculoskelet Disord 2008;9:77.

24hr

Post-operative time

48hr

7 day

CELECOXIB vs. diclofenac:

Acute Ankle Sprain
Nadarajah et al. 2006: Patient Recovery

% of patients

Percentage of patients recovered at day 8

celecoxib
diclofenac

Normal
Function
Nadarajah A et al. Singapore J Med 2006;47:554.

Improved
2 grades

Improved
1 grade

CELECOXIB vs. diclofenac:

Acute Ankle Sprain
Nadarajah et al. 2006: VAS Score
VAS pain scores during treatment phase
70

Mean VAS Score

60
50
40
celecoxib
diclofenac SR

30
20
10
0
0

Days
VAS=visual analogue scale.
Nadarajah A et al. Singapore J Med 2006;47:554.

CELECOXIB vs. diclofenac:

Acute Low Back Pain Trial
Rahla et al. 2008: Change from Baseline in VAS
Change from baseline

VAS (mm)

Less pain

Day 3

celecoxib 200 mg BID (n=123)

diclofenac 75 mg BID (n=121)

VAS=visual analogue scale.

Rahla L et al. Abstract P025. APLAR J Rheumatol 2006;9(Suppl 1): A21A278.

Day 7

CELECOXIB vs. diclofenac:

Acute Low Back Pain Trial
Rahla et al. 2008: Patients Global Assessment
Patients global assessment of study medication at day 3 and day 7

Percentage of patients (%)

celecoxib 200 mg BID (n=123)

diclofenac 75 mg BID (n=121)

Day 3
Rahla L et al. Abstract P025. APLAR J Rheumatol 2006;9(Suppl 1): A21A278.

Day 7

CELECOXIB
safety and tolerability
Cardiovascular safety profile

APTC Composite End Point (Adjudicated):

Celecoxib vs ns-NSAIDs
Meta-analysis of 25 RCTs

Relative Risk (CI) of Serious

CV Adverse Events

2.0

P =.59 (NS)

1.5

1.0

1.0
49 events

0.90
(95% CI: 0.60-1.33)
54 events

0.5

09/25/09
White et al. Am J Cardiol. 2007.

ns-NSAIDs
(n=13,990)

Celecoxib 200-800 mg daily

(n=19,773)

CELECOXIB vs. naproxen & etoricoxib:

CV Safety Profile
Schwartz et al. 2007: Blood pressure change

Systolic blood pressure, mm Hg

Average blood pressure over a 24-hour period between days 1-14

9
8
7
6
5
4
3
2
1
0

7.7

3.6
2.4

celecoxib 200 mg BID (n=21)

+
+

++

naproxen 500 mg BID (n=21)

etoricoxib 90 mg OD (n=21)

Compared to naproxen and etoricoxib, celecoxib only shows significant change compared to placebo. Meanwhile etoricoxib shows significant
increase compared to placebo, baseline, and celecoxib and naproxen.
+ Significantly different from placebo (P .05)
* Significantly different from baseline (P .05), placebo (P .05), and naproxen and celecoxib (P < .03)
Schwartz JI et al. J Clin Pharmacol 2007;47:1521-31.

Coxibs vs. ns-NSAIDs: GI and CV Benefit/Risk Profile

Moore et al. 2007: GI and CV Event Rates
Favours coxib

Favours ns-NSAID

celecoxib
etoricoxib

lumiracoxib
all coxibs

Event rate difference (coxib-NSAID per 1000 per year)

celecoxib Annually, per 1,000 patients, there

were:
12 fewer upper GI complications
2 fewer fatal/non-fatal heart attacks or strokes
Moore RA et al. BMC Musculoskelet Disord 2007;8:73.

GI bleed difference
CV event dfifference

CELECOXIB
safety and tolerability
Other adverse events

CELECOXIB vs. diclofenac

Dahlberg et al. 2009: CV / renal & hepatic AEs

One-year, randomized, multicentre, double-blind, parallel-group study to assess the AE-related discontinuation rate with celecoxib and diclofenac in elderly
patients with OA.
No p-values reported for related/not-related-to-treatment incidence. Significantly fewer patients in the celecoxib group than the diclofenac group experienced
cardiovascular/renal AEs (70/458 vs. 95/458, p=0.039) or hepatic AEs (10/458 vs. 39/458, p<0.0001).
Dahlberg LE et al. Scand J Rheumatol 2009;38:133-143.

CELECOXIB vs. diclofenac + omeprazole:

Renal Safety Profile
Chan et al. 2002: Incidence of renal adverse events

Six-months, prospective, randomized, double-blind trial.

Objective: To compare celecoxib, diclofenac + omeprazole in reducing risk of recurrent ulcer bleeding in patients at high risk of bleeding.
Renal AEs included hypertension, peripheral edema, and renal failure.
Chan FKL et al. N Engl J Med 2002;347:2104-2110.

CELECOXIB vs. ns-NSAIDs:

Hepatic Safety Profile
Sanchez-Matienzo et al. 2006: Prevalence of hepatic events

A case/noncase analysis of spontaneous reports was conducted to compare the hepatic safety profile of COXIBs and ns-NSAIDs.
Sanchez-Matienzo D et al. Clin Ther 2006;28:1123-1132.

Risk of Ischemic Stroke with Current

NSAID Use

Study design: Nested case-control study to evaluate the risk of ischemic stroke in 469,674 patients
from the UK General Practice Research Database (GPRD) who had been prescribed at least one
NSAIDs between June 1, 2000 and October 31, 2004. The NSAIDs prescribed were celecoxib,
rofecoxib, etoricoxib, diclofennac, ibuprofen, naproxen, and other NSAIDs

09/25/09

Andersohn F et al. Stroke 2006;37:17251730

CELECOXIB
safety and tolerability
Gastrointestinal Safety Profile

CELECOXIB vs. naproxen/diclofenac:

12-week OA Trial (SUCCESS-I)
Singh et al. 2006: Primary safety analysis*
Ulcer Complications and Ulcer Complications/Symptomatic Ulcers
celecoxib (n=8800)

Rate/100 Patient-Years

ns-NSAIDS (n=4394)
p=0.008

Ulcer Complications

Ulcer Complications/
Symptomatic Ulcers

7x lower chance of ulcer complications per 100 patient-years vs.

ns-NSAIDs in OA patients
SUCCESS=Successive Celecoxib Efficacy and Safety Study.
* Adjudication based on lesions.

Perforations, ulcer bleeding, obstructions.

Symptomatic ulcers documented by endoscopy or upper GI barium radiography and with no evidence of GI bleeding.

Singh G et al. Am J Med 2006;119:255-266.

CELECOXIB vs. placebo:

GI Safety Profile
Feng et al. 2008: Incidence of GI ulcers
Incidence of gastrointestinal ulcers

Incidence (%)

5
4

3.7

3.3

3
2
1
0
celecoxib (n=463)

placebo (n=473)

Celecoxib shows a similar GI incidence compared to placebo.

Feng GS et al. Celecoxib-related gastroduodenal ulcer and cardiovascular events in a randomized trial for gastric cancer prevention
World J Gastroenterol 2008;14:4535-4539

Guidelines for Prevention of

NSAID-Related Ulcer Complications
(ACG Practice Guidelines 2009)

Lanza FL et al. Am J Gastroenterol 2009;104:728-738

UPDATE!

2009
CONDOR
2011
GI-REASONS
2012
SCOT
2013
PRECISION
09/25/09

Study of Celecoxib or Diclofenac and Omeprazole for GI

safety in high GI risk patients with arthritis
Celecoxib GI safety compared with ns-NSAID + PPI
4,400 OA/RA patients at high risk of GI events
Already published on Lancet in July 2010!

GI safety of celecoxib compared with NSAIDs

Celecoxib GI safety compared with ns-NSAIDs
8,000 OA patients
Still ongoing

The Standard Care vs. Celecoxib Outcome Trial

Celecoxib CV safety compared with ns-NSAIDs
1,600 OA/RA patients

Prospective Randomized Evaluation of Celecoxib Integrated

Safety vs. Ibuprofen or Naproxen
Celebrex CV safety compared with ibuprofen and naproxen
20,000 OA/RA patients with or at risk of developing CV disease

Celecoxib versus omeprazole

and diclofenac in patients with
osteoarthritis and rheumatoid
arthritis (CONDOR)
Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

 Objective:
To compare risk of GI events associated with celecoxib vs
diclofenac SR + omeprazole
Methodology:
6-month, double-blind, randomised trial in 4,484 patients (ITT) with
OA or RA at increased GI risk
196 centres in 32 countries or territories
Celecoxib 200 mg BID OR diclofenac SR 75 mg BID + omeprazole
20 mg OD
Primary endpoint: a composite of clinically significant upper or
lower GI events adjudicated by an independent committee.
Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

Inclusion Criteria

Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

Result

Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

CONDOR 2010
Patient with celecoxib has lower risk on gastrointestinal events than those with
diclofenac SR + omeprazole
(81 events, 95% CI,
2.9-4.3)

(20 events, 95% CI, 0.51.3)

P<0.0001
Chan FKL et al. Lancet 2010; DOI:10.1016/S0140-6736(10)60673-3

Conclusion CONDOR
Study
Risk of clinical outcomes throughout the GI tract
was lower in patients treated with a COX-2selective NSAID than in those receiving a nonselective NSAID plus a PPI.
Celecoxib, when used alone, carries less risk of
clinically significant events through the entire GI
tract when compared with diclofenac +
omeprazole

Chan FKL et al. Lancet 2010. DOI:10.1016/S0140-6736(10)60673-3

SUMMARY
Pain as resulted by chronic diseases and acute
conditions, is a major health problem
COX-2 inhibitors relief pain by selectively inhibit
COX-2 enzyme which is mainly responsible for
inflammation and pain process
Celecoxib is scientifically proven to alleviate
chronic and acute pain
Celecoxib is THE ONLY COXIB APPROVED by US
FDA
Celecoxib has a well-tolerated safety profile

THANK YOU

BACK UP SLIDES

09/25/09

CELECOXIB vs. paracetamol:

12-week OA Trial
Pincus et al. 2004: Patient Preference
Patient preference in PACES-a

Patients %

*p<0.001 vs paracetamol

celecoxib
200 mg
Once-daily

paracetamol
1,000 mg
4 times daily

PACES=Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies.

Pincus T et al. Ann Rheum Dis 2004;63:931-939.

CELECOXIB vs. diclofenac:

6-month RA Trial

Percentage of patients (%)

Shi et al. 2004: Study withdrawl due to lack of efficacy

celecoxib
200 mg/d
(n=55)
Shi W et al. Clin Drug Invest 2004;21:81-101.

diclofenac
75-100 mg/d
(n=131)

nabumetone
1000 mg/d
(n=131)

meloxicam
15 mg/d
(n=144)

CELECOXIB vs. diclofenac:

6-month RA Trial

ADR incidence (%)

Shi et al. 2004: Adverse Drug Reactions (ADR)

celecoxib
200 mg/d
(n=55)

Shi
W et al.
Drug Invest
2004;21:81-101.
* p<0.05
vs.Clin
diclofenac,
nabumetone
and meloxicam.

diclofenac
75-100 mg/d
(n=131)

nabumetone
1000 mg/d
(n=131)

meloxicam
15 mg/d
(n=144)

CELECOXIB: Post-Oral Surgery

Cheung et al. 2007: Rescue Medication

Percentage (%)

Percentage of patients requiring rescue medication

celecoxib
400 mg (n=57)

ibuprofen
400 mg (n=57)

Cheung R et al. Clin Ther 2007;29 Suppl:2498-2510.

placebo
(n=57)

CELECOXIB vs. ns-NSAIDs:

CV Safety Profile
White et al. 2007: Meta-Analysis
Non-Adjudicated
Relative Risk (95%CI)

Favours
celecoxib

White WB et al. Am J Cardiol 2007;99:91-98.

Favours
Ns-NSAIDS

Adjudicated
Relative Risk (95%CI)

Favours
celecoxib

Favours
Ns-NSAIDS

CELECOXIB vs. ns-NSAIDs:

CV Safety Profile
White et al. 2007: CV Risk Ratios
Rate/100 patient-years

celecoxib
Ns-NSAIDs

APTC
Composite

APTC=Antiplatelet Trialists' Collaboration.

MI=myocardial infarction.

CV Deaths

Nonfatal MI Nonfatal Stroke

OSTEOARTHRITIS

09/25/09

Consensus definition of OA
OA disease are manifested by morphologic, biochemical,
molecular, and biomechanical changes of both cells and
matrix which lead to a softening, fibrillation and eburnation
of sub-chondral bone, osteophytes, and sub-chondral cysts.

Clinically evident characterized by joint pain, tenderness,

limitation of movement, crepitus, occasional effusion, and
variable degrees of inflammation without systemic effect.

Kuettner KE, et al. Am Acad Orthop Surg,1999

Epidemiology and Impact of Osteoarthritis

Most common form of arthritis1
Osteoarthritis affects 40 million Americans1
Estimated to affect 59.4 million people, or 18.2% of the US
population, by 20201
>20 million people experience pain from osteoarthritis2
7.1 million ambulatory care visits specific to osteoarthritis3
Leading cause of work-related disability in people aged
16-72 years1
80% of people >75 years have osteoarthritis4

1. Lawrence RC et al. Arthritis Rheum. 1998;41:778-799. 2. Lipman AG. Curr Rheumatol Rep. 2001;3:513-519. 3. Hootman JM
et al. Arthritis Rheum. 2002;47:571-581. 4. Manek NJ, Lane NE. Am Fam Physician. 2000;61:1795-1804.

Joints Commonly Involved

in Osteoarthritis
Osteoarthritis principally affects weightbearing joints in the knees and hips.
Also affects the feet, ankles, distal
interphalangeal joints, proximal
interphalangeal joints, first
carpometacarpal joints, cervical spine,
and lower spine

APS. Guideline for the Management of Pain in Osteoarthritis, Rheumatoid Arthritis, and Juvenile Chronic Arthritis. 2nd ed.
Glenview, Ill: American Pain Society; 2002.

Synovial
membrane

Cyst formation
and sclerosis in
subchondral bone
Shelving fibrillated
cartilage

Cartilage

Osteophytic lipping
Synovial
hypertrophy

Capsule
Bone

Normal

Thickened
capsule

Osteoarthritis

Management of
Osteoarthritis

09/25/09

Osteoarthritis Therapy in Indonesia

IRA Recommendation
(Consensus statement on OA, 2003)

Four pillars
Education
Medical rehabilitation program (physical therapy,
walking aid, etc.)
Pharmacology therapy
Surgical management

Osteoarthritis Therapy in Indonesia

IRA Recommendation
(Consensus statement on OA, 2003)

Pharmacology therapy
Analgesics
Acetaminophen
NSAIDs
Tramadol and opioids

Topical
Topical NSAIDs

Intra-articular
Corticosteroids
Hyaluronan

Symptomatic slow acting drugs

Glucosamine sulfate
Chondroitin sulfate
Diacerein

2008 statement, revised in progress

OARSI recommendations for the

management of hip and knee
osteoarthritis, Part II: OARSI
evidence-based, expert consensus
guidelines (2008)

OARSI recommendations
for the management of hip and knee OA
1. Optimal management of OA requires a combination of
non-pharmacological and pharmacological modalities.
SOR: 96% (95% CI 93-99)
2. Patients with hip and knee OA should be encouraged to
undertake, and continue to undertake, regular aerobic,
muscle strengthening and range of motion exercises.
SOR: 96% (95% CI 93-99)
3. Patients with hip and knee OA, who are overweight,
should be encouraged to lose weight and maintain their
weight at a lower level. SOR: 96% (95% CI 92-100)

OARSI recommendations
for the management of hip and knee OA
4. Acetaminophen can be an effective initial oral analgesic for
treatment of mild to moderate pain in patients with knee or
hip OA. In the absence of an adequate response, or in the
presence of severe pain and/or inflammation, alternative
pharmacologic therapy should be considered based on
relative efficacy and safety, as well as concomitant
medications and comorbidities. SOR: 92% (95% CI 88e99)
5. In patients with symptomatic hip or knee OA, non-steroidal
anti-inflammatory drugs (NSAIDs) should be used at the
lowest effective dose but their long-term use should be
avoided if possible. SOR: 93% (95% CI 88e99)

OARSI recommendations
for the management of hip and knee OA
6. Intra-articular (IA) injections with corticosteroids can be
used in the treatment of hip or knee OA, and should be
considered particularly when patients havemoderate to
severe pain not responding satisfactorily to oral
analgesic/anti-inflammatory agents and in patients with
symptomatic knee OA with effusions or other physical
signs of local inflammation. SOR: 78% (95% CI 61e95)
Injections of IA hyaluronate may be useful in patients with
knee or hip OA. They are characterised by delayed
onset, but prolonged duration, of symptomatic benefit
when compared to IA injections of corticosteroids. SOR:
64% (95% CI 43e85)

RHEUMATOID ARTRITIS
Chronic systemic autoimmune inflammatory
disease , especially affected small joint,
leading to joint destruction and disability
Joint destruction mostly in first 2 year
Early aggressive treatment with DMARDs is
needed to achieve the greatest effect on long
term outcome
Prevalence: - 1 % (USA)
- 0.2 - 0.6 % (Asia)

Female : male = 3 : 1

RA is Characterised by Synovitis and

Joint Destruction
Synovial
membrane

NORMAL

Inflamed
synovial
membrane

RA

Pannus
Cartilage

Major cell types:

T lymphocytes
macrophages
Minor cell types:
fibroblasts
plasma cells
endothelium
dendritic cells

Synovial
fluid

Capsule

Cartilage thinning
Adapted from Feldmann M, et al. Ann Rev Immunol. 1996;14:397-440;
Pincus T. Drugs. 1995;50(suppl 1):1-14; Tak P, Bresnihan B. Arthritis Rheum. 2000;43:2619-2633.

Major cell type:

neutrophils

Rheumatoid Arthritis:
Goal of Treatment
Remission
1. Pain control
2. Maintan joint fuction for essential and
daily activity
3. Optimize QOL
4. Prevent or inhibit joint destruction

NSAIDs
The NSAIDs are used to modify the symptoms of RA.
The use of NSAIDs is recommended at disease onset, when a
new DMARD is introduced, and occasionally when
uncontrolled isolated symptoms persist despite good
response to a DMARD.
The need for continuous use of NSAIDs in a patient with RA
should be interpreted as inadequate control of inflammatory
activity and should, therefore, lead to reassessment of the
DMARD regimen.

NSAIDs
All NSAIDs should be used at the full dose for at
least 1 week before considering the treatment
to have failed. Once symptoms have been
controlled, the minimum effective dose should
be used.
There is no evidence that some NSAIDs are
better than others, but vary in their potential
gastrointestinal, liver and cardio-renal toxicity;
therefore, when choosing the agent and dose,
healthcare professionals should take into
account individual patient risk factors

Example of co-existing pain:

Herniated disc causing low back pain and
lumbar radiculopathy
Activation of peripheral nociceptors
cause of nociceptive pain component
Disc herniation

Lumbar
vertebra

Compression and inflammation of nerve root

cause of neuropathic pain component
09/25/09