Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison

Background Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxy genase (COX), which leads to suppression of COX-1-mediated production of ga strointestinal-protective prostaglandins. Gastrointestinal injury is a comm on outcome. We compared the efficacy, safely, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofena c, a non-specific COX inhibitor. Methods 655 patients with adult-onset rheumatoid arthritis of at least 6 mo nths' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analges ic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal e ndoscopy within 7 days of the last treatment dose at centres where the proc edure was available. Analysis was by intention-to-treat, Findings 430 patients underwent endoscopy (celecoxib n=212, diclofenac n=21 8). The two drugs were similar in management of rheumatoid arthritis pain a nd inflammation. Gastroduodenal ulcers were detected endoscopically in 33 ( 15%) patients treated with diclofenac and in eight (4%) in the celecoxib gr oup (p<0.001). The rate of withdrawal for any gastrointestinal-related adve rse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was near ly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001). Interpretation Celecoxib showed sustained anti-inflammatory and analgesic a ctivity similar to diclofenac, with a lower frequency of upper gastrointest inal ulceration or gastrointestinal adverse events, and tolerability was be tter.