A pooled analysis of two randomized, double-blind, placebo-controlled trials of milnacipran monotherapy in the treatment of fibromyalgia

Abstract

Effective fibromyalgia (FM) treatment requires identification of well-tolerated medications that improve pain and other associated FM symptoms. In 2 randomized, placebo-controlled trials, milnacipran improved multiple FM symptoms and was safe and well-tolerated. To validate these findings, a post hoc analysis of pooled data from these studies was conducted. Both trials were similar in patient selection, study design, and efficacy assessments. Patients received placebo (n = 624), milnacipran 100 mg/day (n = 623), or milnacipran 200 mg/day (n = 837). Two composite responder definitions were used to classify each patient's individual response to therapy. FM responders (overall responders) concurrently satisfied response criteria for clinically meaningful improvements of pain (≥30% improvement from baseline in VAS 24-hour recall pain scores), Patient Global Impression of Change (PGIC, rating of “very much improved” or “much improved”), and physical functioning (≥6-point improvement from baseline in SF-36 PCS scores). FM pain composite responders concurrently satisfied response criteria for clinically meaningful improvements in pain and PGIC. Pooled results at 15 weeks were analyzed by linear mixed-effect models. The percentage of patients who were overall responders was significantly greater in each milnacipran treatment group (23.6%, 200 mg/day; 21.1%, 100 mg/day) compared to placebo (9.6%) (each dose vs placebo, P < .001). Likewise, a significantly greater proportion of milnacipran-treated patients were considered FM pain composite responders (42.8%, 200 mg/day; 36.8%, 100 mg/day) compared to placebo (20.6%) (each dose vs placebo, P < .001). Analysis of individual outcomes indicated significant improvements from baseline with each milnacipran dose compared to placebo in pain (P < .05), global status (P < .001), physical functioning (P < .01), and fatigue (Multidimensional Fatigue Inventory, MFI) (P < .05) at 15 weeks; cognition (Multiple Ability Self-report Questionnaire, MASQ) significantly improved with milnacipran 200 mg/day (P < .01). These results further support the conclusion that milnacipran is effective for the treatment of FM and its associated symptoms. (Supported by Forest Laboratories, Inc. and Cypress Bioscience, Inc.)