Long-Term Treatment for Fibromyalgia with Milnacipran

Palm Springs—Patients diagnosed with fibromyalgia experience widespread pain and other chronic conditions that often negatively affect function and lead to decreased health-related quality of life. A major therapeutic goal in the management of fibromyalgia is identifying a treatment that includes clinical efficacy as well as tolerability. In previous clinical trials, milnacipran was shown to improve pain and other fibromyalgia symptoms and demonstrated durable efficacy for up to 1 year in follow-up studies. Researchers recently conducted a multicenter, open-label, flexible-dose study to assess the long-term efficacy, safety, and tolerability of milnacipran in patients with fibromyalgia. They reported study results at the AAPM meeting in a poster titled A Three-Tier, Open-Label, Flexible-Dosing Study of Milnacipran for the Treatment of Fibromyalgia. Study participants were patients diagnosed with fibromyalgia as defined by the American College of Rheumatology 1990 criteria who had completed a previous milnacipran study or were active in a milnacipran study when it was administratively ended. The current study included 4 phases: a 2-week washout/run-in phase; a 2-week dose escalation to milnacipran 100 mg/day; 8 weeks at a stable dose of 100 mg/day; and a flexible-dose phase, 50 to 200 mg/day based on tolerability or efficacy for the remainder of the study period. After applying exclusion criteria, the study included 1220 participants. Mean age was 50.3 years, 95.4% (n=1164) were female, 93.1% (n=1136) were white, and mean body mass index was 30.7 kg/m2. The mean daily last dose of milnacipran was 140.1 mg/day, and the mean duration of milnacipran treatment was 18.5 months. Patients treated with milnacipran had improvements in pain, global status, and functioning. The cohort of patients who completed ≥3 years in the study had slightly greater mean improvements in all outcomes compared with the overall intent-to-treat population (which included patients who dropped out of the study early). In the cohort completing ≥3 years, treatment with milnacipran resulted in a mean improvement from baseline in pain of 23.9 points at the final visit (a 38% mean decrease in pain after 3 years of treatment). Of the patients in the ≥3-year cohort, 70.3% were Patient Global Impression of Change responders; those patients gave a rating of 1 (very much improved) or 2 (much improved) at their last study visit. Adverse events leading to discontinuation of the study treatment occurred in 20.5% of patients. The most common adverse events leading to discontinuation were nausea (2.7%), hypertension (1.7%), hyperhidrosis (1.5%), hot flush (1.3%), depression (1.3%), palpitations (1.3%), and headache (1.1%). The most commonly reported treatment emergent adverse events (TEAEs) were nausea and headache; the researchers noted that the incidences of nausea and headache in this study were lower than those reported in previous, shorter placebo-controlled trials. Most TEAEs were mild or moderate (89.5%); 64.4% were judged unrelated to milnacipran, 29.6% were judged possibly related, and only 6.0% were judged related to the study medication. In conclusion, the researchers noted that improvements in pain, global status, and physical functioning were maintained with long-term milnacipran treatment. The improvements were achieved by month 3 of treatment and sustained for the entire study period of up to 3.25 years. Of the patients who completed 3 years of treatment, 70% demonstrated clinically significant improvements in global status. The researchers added that, “no new safety concerns were observed in patients with fibromyalgia receiving long-term milnacipran treatments.”