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

Lancet. 1999 Dec 18-25;354(9196):2106-11. doi: 10.1016/S0140-6736(99)02332-6.

Abstract

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.

Findings: 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).

Interpretation: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Blood Pressure / drug effects
  • Celecoxib
  • Cyclooxygenase Inhibitors / adverse effects
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Diclofenac / adverse effects
  • Diclofenac / therapeutic use*
  • Double-Blind Method
  • Female
  • Hemoglobins / drug effects
  • Humans
  • Male
  • Middle Aged
  • Pain Measurement
  • Pyrazoles
  • Stomach Ulcer / chemically induced
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Hemoglobins
  • Pyrazoles
  • Sulfonamides
  • Diclofenac
  • Celecoxib