Comparing the efficacy of cyclooxygenase 2-specific inhibitors in treating osteoarthritis - Appropriate trial design considerations and results of a randomized, placebo-controlled trial

Objective. To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA). Methods. In this randomized, placebo-controlled, double-blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination). Results. In primary measures of efficacy (OA pain score on a 100-mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34-mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was -2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events. Conclusion. Celecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.