Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs

Academic Article


  • Context: Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) toxic effects, such as upper GI tract perforations, symptomatic gastroduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be attributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically inhibits COX-2 and has demonstrated a low potential for causing upper GI injury. Objective: To compare the incidence of PUBs in patients with osteoarthritis treated with rofecoxib vs NSAIDs. Design: Prespecified analysis of all 8 double-blind, randomized phase 2b/3 rofecoxib osteoarthritis trials conducted from December 1996 through March 1998, including one 6-week dose-ranging study, two 6-week efficacy studies vs ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-month endoscopy studies vs ibuprofen and placebo, and one 6-week efficacy study vs nabumetone and placebo. Setting: Multinational sites. Participants: Osteoarthritis patients (N = 5435; mean age, 63 years [range, 38-94 years]; 72.9% women). Interventions: Rofecoxib, 12.5, 25, or 50 mg/d (n = 1209, 1603, and 545, respectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclofenac, 50 mg 3 times per day (n = 590); or nabumetone, 1500 mg/d (n = 127) (combined). Main Outcome Measure: Cumulative incidence of PUBs for rofecoxib vs NSAIDs, based on survival analysis of time to first PUB diagnosis, using PUBs that met prespecified criteria judged by a blinded, external adjudication committee. Results: The incidence of PUBs over 12 months was significantly lower with rofecoxib vs NSAIDs (12-month cumulative incidence, 1.3% vs 1.8%; P = .046; rate per 100 patient-years, 1.33 vs 2.60; relative risk, 0.51; 95% confidence interval, 0.261.00). The cumulative incidence of dyspeptic GI adverse experiences was also lower with rofecoxib vs NSAIDS over 6 months (23.5% vs 25.5%; P= .02), after which the incidence rates converged. Conclusion: In a combined analysis of 8 trials of patients with osteoarthritis, treatment with rofecoxib was associated with a significantly lower incidence of PUBs than treatment with NSAIDs.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Langman MJ; Jensen DM; Watson DJ; Harper SE; Zhao PL; Quan H; Bolognese JA; Simon TJ
  • Start Page

  • 1929
  • End Page

  • 1933
  • Volume

  • 282
  • Issue

  • 20