Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo

OBJECTIVE: To determine the upper gastrointestinal (GI) tolerability of celecoxib, naproxen, and placebo in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: An analysis of 5, 12-week, randomized, double blind, parallel group, placebo controlled clinical trials was conducted. In these trials, patients were randomized to: naproxen 500 mg bid (n = 1,099), placebo (n = 1,136), celecoxib 50 mg bid (n = 690) (subtherapeutic dose), celecoxib 100 mg (n = 1,131) or 200 mg bid (n = 1,125) (therapeutic dose), or celecoxib 400 mg bid (n = 434) (supratherapeutic dosage). The incidence and time until moderate to severe abdominal pain, dyspepsia, nausea, and any of the aforementioned 3 upper GI symptoms (composite endpoint) were determined using time-to-event analysis. RESULTS: The cumulative incidences of moderate to severe abdominal pain, dyspepsia, or nausea (composite endpoint) were: naproxen 500 mg (12.0%; 95% CI 9.9%-14.0%), celecoxib 50 mg bid (7.1%; 95% CI 5.0%-9.2%), celecoxib 100 mg bid (7.8%; 95% CI 6.0%-9.5%), celecoxib 200 mg bid (8.1%; 95% CI 6.4%-9.9%), celecoxib 400 mg bid (6.0%; 95% CI 3.6%-8.4%), and placebo (8.5%; 95% CI 6.5%-10.8%). After controlling for independent predictors of the composite endpoint, relative risks (RR) for the various treatments relative to naproxen 500 mg bid were: celecoxib 50 mg (RR 0.54; 95% CI 0.37-0.77; p < 0.001), celecoxib 100 mg (RR 0.60; 95% CI 0.45-0.80; p < 0.001), celecoxib 200 mg bid (RR 0.63; 95% CI 0.47-0.83; p = 0.001), celecoxib 400 mg bid (RR 0.56; 95% CI 0.35-0.89; p = 0.015), and placebo (RR 0.63; 95% CI 0.47-0.85; p = 0.002). After controlling for independent predictors of the composite endpoint, celecoxib treatment group patients did not differ from placebo patients when reporting the composite endpoint, with p values ranging from 0.40 to 0.96. CONCLUSION: The upper GI tolerability of celecoxib is superior to naproxen. A dose-response relationship between celecoxib and upper GI symptoms was not apparent.