A randomized, double-blind, placebo-controlled discontinuation study of milnacipran for the treatment of fibromyalgia in patients receiving long-term milnacipran treatment

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This 17-week, multicenter, double-blind (DB), placebo-controlled discontinuation study was designed to evaluate the efficacy of milnacipran for the treatment of fibromyalgia in patients receiving long-term milnacipran treatment. Patients completing a long-term (up to 3.25 years) open-label (OL) extension study of milnacipran 50 to 200 mg/day were eligible to participate. After completing 4-weeks of OL milnacipran treatment, patients taking milnacipran ≥100 mg/day and achieving a ≥50% reduction in visual analog scale (VAS) pain score from pre-milnacipran exposure to current status (ie, the primary outcome analysis population) were randomized 2:1 to DB treatment with milnacipran or placebo for 12 weeks. Patients assigned to milnacipran remained on the same dose as in the previous OL study. The primary efficacy parameter was the time to loss of therapeutic response (LTR), defined as an increase in VAS pain score to <30% reduction from pre-milnacipran exposure or a worsening of fibromyalgia requiring an alternative treatment. Time to LTR was analyzed by using Kaplan-Meier estimates by treatment group and the log-rank test. Time to LTR was significantly shorter for patients treated with placebo (n=50) than milnacipran (n=100, P=0.0004). The median time to LTR was 56 days (95% CI, 28-85) for patients treated with placebo and not calculable for patients treated with milnacipran since half of these patients had not lost therapeutic response by study end. At the end of DB treatment, 64% of placebo patients met LTR criteria vs 35% of milnacipran patients. Discontinuation due to treatment-emergent adverse events occurred in 2 milnacipran-treated patients (2.0%) and no placebo-treated patients. In patients who have been treated with milnacipran for up to 3.25 years, the loss of therapeutic response upon discontinuation of treatment provides further evidence of the efficacy of milnacipran as a treatment for fibromyalgia. This 17-week, multicenter, double-blind (DB), placebo-controlled discontinuation study was designed to evaluate the efficacy of milnacipran for the treatment of fibromyalgia in patients receiving long-term milnacipran treatment. Patients completing a long-term (up to 3.25 years) open-label (OL) extension study of milnacipran 50 to 200 mg/day were eligible to participate. After completing 4-weeks of OL milnacipran treatment, patients taking milnacipran ≥100 mg/day and achieving a ≥50% reduction in visual analog scale (VAS) pain score from pre-milnacipran exposure to current status (ie, the primary outcome analysis population) were randomized 2:1 to DB treatment with milnacipran or placebo for 12 weeks. Patients assigned to milnacipran remained on the same dose as in the previous OL study. The primary efficacy parameter was the time to loss of therapeutic response (LTR), defined as an increase in VAS pain score to <30% reduction from pre-milnacipran exposure or a worsening of fibromyalgia requiring an alternative treatment. Time to LTR was analyzed by using Kaplan-Meier estimates by treatment group and the log-rank test. Time to LTR was significantly shorter for patients treated with placebo (n=50) than milnacipran (n=100, P=0.0004). The median time to LTR was 56 days (95% CI, 28-85) for patients treated with placebo and not calculable for patients treated with milnacipran since half of these patients had not lost therapeutic response by study end. At the end of DB treatment, 64% of placebo patients met LTR criteria vs 35% of milnacipran patients. Discontinuation due to treatment-emergent adverse events occurred in 2 milnacipran-treated patients (2.0%) and no placebo-treated patients. In patients who have been treated with milnacipran for up to 3.25 years, the loss of therapeutic response upon discontinuation of treatment provides further evidence of the efficacy of milnacipran as a treatment for fibromyalgia.