Dose response and safety study of meloxicam up to 22.5 mg daily in rheumatoid arthritis: a 12 week multicenter, double blind, dose response study versus placebo and diclofenac.

OBJECTIVE

This Phase III, placebo and active controlled, multicenter trial evaluated the efficacy and safety of meloxicam 7.5, 15, and 22.5 mg daily for the treatment of rheumatoid arthritis (RA).

METHODS

A 12 week, randomized, double blind, double dummy, parallel group trial compared daily oral meloxicam 7.5, 15, and 22.5 mg to placebo (negative control) and diclofenac 75 mg BID (positive control). A total of 894 patients (18 years of age with confirmed RA who flared following an NSAID-free period) were randomized to be treated. Baseline scores for all endpoints were similar among the treatment groups. Patient assessments were at 0, 2, 4, 8, and 12 weeks or early termination.

RESULTS

All treatment groups demonstrated significant improvement from baseline (p < 0.001). Meloxicam 7.5 and 22.5 mg was significantly superior to placebo in all 5 primary efficacy endpoints (swollen joint count, tender joint count, patient pain, patient and physician global; all p < 0.05). Diclofenac 150 mg was superior to placebo for 4 of 5 primary efficacy measures (all but swollen joint count; p < 0.05) and meloxicam 15 mg was superior for 3 of 5 primary endpoints (patient pain and patient and physician global). AUC of patient global, patient pain, and modified Health Assessment Questionnaire demonstrated dose-response (p < 0.04), while AUC ACR20 showed a qualitative trend in the same direction. The rate of gastrointestinal (GI) events during the 12 week trial for all doses of meloxicam and diclofenac did not differ significantly from placebo (23.2-32.0%). GI withdrawals were comparable and not significantly different across all treatment groups (4.3-5.7%).

CONCLUSION

This trial demonstrated a dose response relationship for meloxicam 7.5, 15, and 22.5 mg using AUC measurement of response for the treatment of RA. All 3 doses of meloxicam. and positive control, were effective in the treatment of RA. The overall incidence rate of GI events did not differ significantly from placebo in either the meloxicam treatment groups or the positive control.