Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX), which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostaglandins. Gastrointestinal injury is a common outcome. We compared the efficacy, safety, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofenac, a non-specific COX inhibitor.


METHODS
655 patients with adult-onset rheumatoid arthritis of at least 6 months' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analgesic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available. Analysis was by intention-to-treat.


RESULTS
430 patients underwent endoscopy (celecoxib n=212, diclofenac n=218). The two drugs were similar in management of rheumatoid arthritis pain and inflammation. Gastroduodenal ulcers were detected endoscopically in 33 (15%) patients treated with diclofenac and in eight (4%) in the celecoxib group (p<0.001). The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001).


CONCLUSIONS
Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac, with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events, and tolerability was better.
Emery
P
P
Department of Rheumatology and Rehabilitation, University of Leeds, UK.
Zeidler
H
H
Kvien
T K
TK
Guslandi
M
M
Naudin
R
R
Stead
H
H
Verburg
K M
KM
Isakson
P C
PC
Hubbard
R C
RC
Geis
G S
GS
D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006454:Hemoglobins / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D011720:Pyrazoles; D013276:Stomach Ulcer / Q000139:chemically induced; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D006454:Hemoglobins; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D000068579:Celecoxib