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Continuing efficacy of milnacipran following long-term treatment in fibromyalgia: a randomized trial.
By Daniel J Clauw, et al.
INTRODUCTION: Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately a year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of milnacipran treatment at time of randomized withdrawal was 36.1 months from initial exposure to milnacipran (range, 17.9 to 54.4 months).
METHODS: After completing a long-term, open-label, lead-in study of milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the 4-week open-label period of the current study for evaluation of ongoing treatment response. After the 4-week period to confirm new baseline status, 151 patients taking milnacipran [greater than or equal to]100 mg/day and reporting [greater than or equal to]50% improvement from pre-milnacipran exposure in visual analog scale (VAS) pain scores were classified as responders.
These responders entered the 12-week, double-blind, withdrawal period in which they were randomized 2:1 to continue milnacipran or switch to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-milnacipran exposure, or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored.
Time to LTR was shorter in patients randomized to placebo than in patients continuing milnacipran (P<0.001).
Median time to LTR was 56 days with placebo and not calculable for milnacipran since less than half of these patients lost therapeutic response by study end.
Additionally, 81% of patients continuing on milnacipran maintained clinically meaningful pain response ([greater than or equal to]30% improvement from pre-milnacipran exposure), compared with 58% of patients switched to placebo (sensitivity analysis II; P<0.001).
Incidence of treatment-emergent adverse events was 58% and 47% for placebo and milnacipran, respectively.
Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo.
CONCLUSIONS: Continuing efficacy of milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of 3 years of milnacipran treatment.
Source: Arthritis Research & Therapy, August 16, 2013. By Daniel J Clauw, Philip J Mease, Robert H Palmer, Joel M Trugman and Yong Wang.