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
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, 0.26-1.00). 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
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.