THE EFFICACY, TOLERABILITY, AND SAFETY OF 1200 MG D OF OXAPROZIN AND 1500 MG/D OF NABUMETONE IN THE TREATMENT OF PATIENTS WITH OSTEOARTHRITIS OF THE KNEE/

This 6-week, multicenter, double-masked, placebo-controlled study comp ared the efficacy, tolerability, and safety of the recommended startin g dose of oxaprozin (1200 mg/d) and a 1500-mg/d dose of nabumetone in the treatment of patients with moderate-to-severe osteoarthritis (OA) of the knee. A total of 347 patients with a mean age of 61.1 years wer e randomized to receive oxaprozin(116 patients), nabumetone (115 patie nts), or placebo (116 patients). Adults of either sex who were older t han 18 years of age were eligible for entry into the study, if they ha d had OA of the knee for at least 6 months. Efficacy variables include d knee pain on weight bearing, knee pain on motion, patients' and phys icians' global assessments of OA, pain intensity as measured on a visu al analog scale, and time to walk 50 feet as quickly as possible. Effi cacy variables were assessed at baseline and at weeks 1, 2, 4, and 6. Between-group differences in efficacy variables were evident by week 1 . Mean improvements were significantly greater with oxaprozin than wit h placebo for all efficacy variables at all time periods, except knee pain on motion at weeks 2 and 4 and time to walk 50 feet at weeks 1, 2 , and 4. Mean improvements were significantly greater with nabumetone than with placebo for all efficacy variables at all time periods, exce pt the following: knee pain on weight bearing at weeks 2, 4, and 6; kn ee pain on motion at weeks 2 and 4; patients' global assessment at wee k 4; and pain intensity as measured on a visual analog scale at weeks 2 and 4. There were, however, no significant differences between oxapr ozin and nabumetone in any of these efficacy variables. Adverse events were reported by 83 (71.6%) patients who took oxaprozin, by 80 (69.6% ) patients who took nabumetone, and by 57 (49.1%) patients who took pl acebo. Adverse events were reported for significantly more patients ta king oxaprozin or nabumetone than placebo. However, adverse events ten ded to be mild or moderate and rarely resulted in patients withdrawing from the study. Combined with the results of an earlier study, the re sults of this study showed that a 1500-mg/d dose of nabumetone, which is higher than the recommended starting dose of 1000 mg/d, is required for efficacy equivalent to that of the recommended starting dose of o xaprozin, 1200 mg/d, in relieving the symptoms of OA. Thus nabumetone may require dosage titration from the recommended starting dose. Oxapr ozin and nabumetone were found to have similar tolerability profiles, as shown by adverse-event monitoring and withdrawal rates, as well as clinically similar safety profiles, as demonstrated by physical examin ations, hematologic and biochemical laboratory testing, hemoccult test ing, and adverse-event monitoring and symptom assessment.