Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs

Context Nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestina l (GI) toxic effects, such as upper GI tract perforations, symptomatic gast roduodenal ulcers, and upper GI tract bleeding (PUBs), are thought to be at tributable to cyclooxygenase 1 (COX-1) inhibition. Rofecoxib specifically i nhibits COX-2 and has demonstrated a low potential for causing upper GI inj ury. 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 r ofecoxib osteoarthritis trials conducted from December 1996 through March 1 998, including one 6-week dose-ranging study, two 6-week efficacy studies v s ibuprofen and placebo, two 1-year efficacy studies vs diclofenac, two 6-m onth endoscopy studies vs ibuprofen and placebo, and one g-week efficacy st udy 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, res pectively, combined) vs ibuprofen, 800 mg 3 times per day (n = 847), diclof enac, 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 commit tee. Results The incidence of PUBs over 12 months was significantly lower with r ofecoxib 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% confiden ce interval, 0.26-1.00). The cumulative incidence of dyspeptic GI adverse e xperiences 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 osteoarthrit is, treatment with rofecoxib was associated with a significantly lower inci dence of PUBs than treatment with NSAIDs.