Evaluation of the comparative efficacy and tolerability of rofecoxib and naproxen in children and adolescents with juvenile rheumatoid arthritis: a 12-week randomized controlled clinical trial with a 52-week open-label extension

• Published in: Journal of rheumatology 2006-05, Vol.33 (5), p.985-995
• Main Authors: Andreas Reiff, Daniel J Lovell, Janet Van Adelsberg, Maria H B Kiss, Steven Goodman, Manuel Ferrandiz Zavaler, Pei-Yun Chen, James A Bolognese, Paul Cavanaugh, Jr, Alise S Reicin, Edward H Giannini
• Format: Article
• Language: English
• Subjects: Adolescent; Arthritis, Juvenile - drug therapy; Arthritis, Juvenile - physiopathology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Child; Child, Preschool; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - blood; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase Inhibitors - adverse effects; Cyclooxygenase Inhibitors - blood; Cyclooxygenase Inhibitors - therapeutic use; Diseases of the osteoarticular system; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Inflammatory joint diseases; Lactones - adverse effects; Lactones - blood; Lactones - therapeutic use; Longitudinal Studies; Male; Medical sciences; Naproxen - adverse effects; Naproxen - blood; Naproxen - therapeutic use; Pharmacology. Drug treatments; Sulfones - adverse effects; Sulfones - blood; Sulfones - therapeutic use; Thiazines - therapeutic use; Thiazoles - therapeutic use; Treatment Outcome
• ISSN: 0315-162X; 1499-2752

OBJECTIVE: To compare the safety and efficacy of rofecoxib* to naproxen for the treatment of juvenile rheumatoid arthritis (JRA). METHODS: This was a 12-week, multicenter, randomized, double-blind, double-dummy, active comparator-controlled, non-inferiority study with a prespecified 52-week open-label active comparator-controlled extension. Children (ages 2-11 yrs) and adolescents (ages 12-17 yrs) received lower-dose (LD)-rofecoxib [0.3 mg/kg/day up to 12.5 mg/day (base study only)]; or higher-dose (HD)-rofecoxib (0.6 mg/kg/day up to 25 mg/day) or naproxen 15 mg/kg/day as oral suspensions. Adolescents received daily rofecoxib (LD) 12.5 (base study only) or (HD) 25 mg, or naproxen 15 mg/kg/day (maximum 1,000 mg/day) as tablets. The primary endpoint was the time-weighted average proportion of patients meeting the American College of Rheumatology Pediatric-30 (ACR Pedi 30) response criteria. A prespecified bound for the 95% confidence interval for the ratio of the percentage of ACR Pedi 30 responders was used to assess non-inferiority of treatment response between groups. Safety was assessed throughout the study. RESULTS: A total of 310 patients ages 2-17 years (181 (3/4) age 11) were randomized to receive LD-rofecoxib (N=109), HD-rofecoxib (N=100), or naproxen (N=101). The ACR Pedi 30 response rates following 12 weeks of treatment were 46.2%, 54.5%, and 55.1%, respectively. The relative rates of response compared to naproxen were 0.81 (95% CI 0.61, 1.07) and 0.98 (95% CI 0.76, 1.26) for LD- and HD-rofecoxib, respectively. Both rofecoxib doses were not inferior to naproxen. Patients (N=227) entering the extension received HD-rofecoxib or naproxen with efficacy maintained during the extension. All treatments were generally well tolerated throughout the study. CONCLUSION: Daily treatment of JRA patients with rofecoxib up to 12.5 or 25 mg was well tolerated, providing sustained clinical effectiveness comparable to naproxen 15 mg/kg. *On September 30, 2004, Merck & Co., Inc. announced the voluntary worldwide withdrawal of rofecoxib from the market.