COMPARISON OF THE EFFICACY AND SAFETY OF OXAPROZIN AND NABUMETONE IN THE TREATMENT OF PATIENTS WITH OSTEOARTHRITIS OF THE KNEE

This multicenter, 6-week, double-blind, placebo-controlled, parallel-g roup study compared the efficacy and safety of oxaprozin 1200 mg once daily with that of nabumetone 1000 mg once daily in patients with mode rate-to-severe osteoarthritis (OA) of the knee. To be eligible, patien ts had to experience a flare of OA within 2 weeks of discontinuing the ir usual OA medication (nonsteroidal antiinflammatory drug or analgesi c). Eligible patients were assessed at baseline and then randomized to receive oxaprozin (n = 109), nabumetone (n = 110), or placebo (n = 10 9). Efficacy assessments were performed at weeks 1, 2, 4, and 6. Prima ry efficacy variables included knee pain on weight bearing, knee pain on motion, and patient's and physician's global assessments of OA. Sec ondary efficacy variables included pain intensity, time to walk 50 fee t, and duration of morning stiffness. Safety was evaluated by use of r outine laboratory analyses; physical examination at screening, baselin e, and week 6 (or study termination); assessment of symptoms at baseli ne and at each visit; and testing stools for occult blood at screening and between week 4 and the final visit. Adverse events were monitored throughout the study. Between-group differences in efficacy variables were evident by week 1. The mean change in improvement from baseline with oxaprozin compared with placebo was statistically significant in favor of oxaprozin at weeks 1, 2, 4, and 6 for all primary efficacy va riables. The mean change in improvement from baseline with nabumetone compared with placebo, however, was statistically significant only at week 1 for knee pain on motion, patient's global assessment, and physi cian's global assessment. The mean change in improvement from baseline was statistically significant (P less than or equal to 0.035) in favo r of oxaprozin versus nabumetone at weeks 2 and 6 for all four primary efficacy variables and also at week 4 for knee pain on motion. The in cidence of adverse clinical events between treatment groups was not st atistically significant. However, nine oxaprozin-treated patients had asymptomatic liver enzyme elevations re; ported as adverse events. Fou r of these patients had reversible elevations of aspartate aminotransf erase and alanine aminotransferase greater than three times the upper limit of normal range (P < 0.05); two of these patients were taking ot her medications known to induce liver enzyme abnormalities. The study showed that oxaprozin 1200 mg once daily was statistically significant ly more efficacious than nabumetone 1000 mg once daily for the treatme nt of patients with moderate-to-severe OA of the knee. Both drugs were clinically well tolerated.