Context: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or specific inhibitors of cyclooxygenase 2 (COX-2). Objective: To assess the relative therapeutic efficacy of rofecoxib, celecoxib, and acetaminophen in adults with OA. Design and Setting: Randomized, parallel-group, double-blind trial, conducted from June 1999 to February 2000, in 29 clinical centers in the United States. Patients: Three hundred eighty-two patients aged at least 40 years who had OA of the knee that was previously treated with NSAIDs or acetaminophen. Interventions: Patients were randomly assigned to receive rofecoxib, 12.5 mg/d (n = 96); rofecoxib, 25 mg/d (n = 95); celecoxib, 200 mg/d (n = 97); or acetaminophen, 4000 mg/d (n = 94) for 6 weeks. Main Outcome Measures: Assessments over days 1 to 6 and over 6 weeks included pain on walking, night pain, pain at rest, and morning stiffness as measured on a Western Ontario McMaster Universities Osteoarthritis Index (100-mm visual analog scale [VAS]) and global response to therapy compared among 4 treatment groups. Results: 79% of patients completed the study. More patients treated with acetaminophen discontinued early due to lack of efficacy than patients treated with COX-2 inhibitors (31% vs 18%-19%). Efficacy assessed in the first 6 days of therapy showed greatest response to rofecoxib, 25 mg/d, followed by rofecoxib, 12.5 mg/d, celecoxib, and acetaminophen, respectively, in terms of relief of pain on walking (-32.2, -29.0, -26.4, and -20.6 mm change on the VAS; P≤.04 for all others vs acetaminophen P=.05 for 25-mg rofecoxib vs celecoxib), rest pain (-21.8, -18.6, -15.5, and -12.5 mm; P≤.02 for either dose of rofecoxib vs acetaminophen and P = .02 for rofecoxib, 25 mg/d, vs celecoxib), night pain (-25.2, -22.0, -18.7, and -18.8 mm; P = .04 for rofecoxib, 25 mg/d, vs both acetaminophen and celecoxib), and morning stiffness (-30.4,-28.4,-25.7, and -20.9 mm; P≤.02 for either dose of rofecoxib vs acetaminophen). Over 6 weeks, rofecoxib, 25 mg/d, provided greatest response for night pain (P<.002 vs celecoxib and P=.006 vs acetaminophen and P=.02 vs rofecoxib, 12.5 mg/d), composite pain subscale (P≤.03 vs all other treatments), stiffness subscale (P≤.04 vs celecoxib and acetaminophen), and physical function subscale (P=.001 vs acetaminophen). Global responses over 6 weeks showed a similar pattern (good or excellent response at week 6: 60%, 56%, 46%, and 39%, respectively; P≤.03 for rofecoxib, 25 mg/d, vs celecoxib and acetaminophen; P=.02 for rofecoxib, 12.5 mg/d, vs acetaminophen). All treatments were generally safe and well tolerated. Conclusion: Rofecoxib, 25 mg/d, provided efficacy advantages over acetaminophen, 4000 mg/d, celecoxib, 200 mg/d, and rofecoxib, 12.5 mg, for symptomatic knee OA.
ASJC Scopus subject areas