Objective: This study compared the efficacy and tolerability of the cyclooxygenase-2-selective inhibitor valdecoxib with the nonselective NSAID naproxen and with placebo in treating severe rheumatoid arthritis (RA).
Methods: This 12-week, multicenter, randomized, double-blind, placebo-controlled study compared the efficacy and tolerability of valdecoxib 10 mg QD (n = 170) or naproxen 500 mg BID (n = 167) with placebo (n = 171) in treating the signs and symptoms of severe RA. Study patients were aged >or=18 years and were diagnosed as having RA for >or=6 months that was stable due to a treatment regimen. Severe RA was defined as a physician's and patient's global assessment of disease activity of fair, poor, or very poor at baseline; >or=6 tender or painful joints; >or=3 swollen joints; >or=45 minutes of morning stiffness; a visual analog scale pain rating of >or=40 mm; or increases since baseline in these measures. Efficacy outcome measures included the percentage of patients achieving an American College of Rheumatology Responder Index 20% (ACR-20) at weeks 1, 6 and 12. Adverse events (AEs) were graded by the investigator as mild, moderate, or severe at weeks 1, 6, and 12.
Results: Of the 508 patients randomized, 340 completed the study. The study groups were comparable for age, ethnic origin, weight, height, and concomitant medications, but the naproxen group had significantly more men (29% [49/167]) than the valdecoxib (18% [31/170]) and placebo (16% [27/171]) groups. The percentage of patients achieving an ACR-20 response was significantly greater in the valdecoxib and naproxen treatment groups (58.8% [100/170] and 60.8% [101/166], respectively) than in the placebo group (39.6% [67/169]) at week 12 (both, P < 0.001). The percentage of patients achieving an ACR-20 response was significantly greater in the naproxen group than in the placebo group at both week 1 (53.6% [89/166] vs 37.9% [64/169]; P = 0.003) and week 6 (64.5% [107/166] vs 46.7% [79/169]; P = 0.001), and in the valdecoxib group compared with placebo at week 1 (52.9% [90/170]; P = 0.008) but not at week 6. Patients in the valdecoxib and naproxen groups had significantly improved efficacy compared with placebo in most of the other secondary assessments of inflammation, pain, and function. The incidence of AEs was similar in all groups (valdecoxib, 54.1% [92/170]; naproxen, 55.4% [92/166]; and placebo, 52.9% [90/170]).
Conclusion: Valdecoxib 10 mg QD administered over 12 weeks was significantly better than placebo and similar to naproxen 500 mg BID in treating the signs and symptoms of severe RA in these patients.