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

Objective. To determine the upper gastrointestinal (GI) tolerability of cel ecoxib, naproxen, and placebo in patients with rheumatoid arthritis (Ra) an d osteoarthritis (OA). Methods. An analysis of 5, 12-week, randomized, double blind, parallel grou p, placebo controlled clinical trials was conducted. In these trials, patie nts were randomized to: naproxen 500 mg bid (n = 1099), placebo (n = 1136), celecoxib 50 mg bid (n = 690) (subtherapeutic dose), celecoxib 100 mg (n = 1131) or 200 mg bid (n = 1125) (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-eve nt analysis. Results. The cumulative incidences of moderate to severe abdominal pain, dy spepsia, or nausea (composite endpoint) were: naproxen 500 mg (12.0%; 95% C I 9.9%-14.0%), celecoxib 50 mg bid (7.1%; 95% CT 5.0%-9.2%), celecoxib 100 mg bid (7.8%; 95% CI 6.0%-9.5%), celecoxib 100 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 composi te endpoint, relative risks (RR) for the various treatments relative to nap roxen 500 mg bid were: celecoxib 50 mg (RR 0.54; 95% CI 0.37-0.77; p < 0.00 1), celecoxib 100 mg (RR 0.60; 95% CI 0.45-0.80; p < 0.001), celecoxib 200 mg bid (RR 0.63: 95% CT 0.47-0.83, p = 0.001), celecoxib 400 mg bid (RR 0.5 6; 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 end point, celecoxib treatment group patients did not differ from placebo patie nts 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 n ot apparent.