Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Safety and Tolerability of Milnacipran in a 3-Year, Open-Label, Flexible-Dosing Study of Patients with Fibromyalgia.
Arnold1, Lesley M., Ma2, Yimin, Palmer2, Robert H., Spera2, Allan, Baldecchi2, Arlene
Milnacipran is a dual serotonin and norepinephrine reuptake inhibitor that is approved in the United States for the management of fibromyalgia (FM). Several clinical trials have shown the efficacy of milnacipran at doses of 100 to 200 mg/day in improving the multidimensional domains of FM, including pain, global status, physical functioning, and fatigue. This open-label study enrolled patients from previous milnacipran trials, some of whom had been taking milnacipran for over 1 year, to assess further its long-term safety and tolerability.
This was a multicenter, open-label, flexible dosing study of up to 3.25 years in duration. A total of 1227 patients with FM who successfully completed a previous milnacipran study were included in this safety analysis. Patients underwent a 2-week washout period, followed by a 2-week dose-escalation period of milnacipran to 100 mg/day. After 8 weeks of dose stabilization at 100 mg/day, patients could have their dose adjusted to between 50 mg/day and 200 mg/day, depending on tolerability and/or therapeutic benefit. Safety assessments included treatment-emergent adverse events (TEAEs) (not present before study drug was taken or that increased in severity during the study period) and vital signs (including weight). In order to adjust for the extended length of time in this study, rates of TEAEs per 100 patient-years were also determined.
The completion rate was 47.7%, comprising 206 patients who reached the final visit and 379 who were enrolled when the study was terminated; discontinuations due to TEAEs were 20.9%. The mean duration of treatment was 563.1 days, with 35.4% of patients completing >=2 years; total exposure to milnacipran was 1889.1 patient-years. The mean daily dose was 133.7 mg/day. TEAEs occurred in 88.3% of patients over the 3.25 year period, with the most commonly reported TEAEs (>=10%) being nausea (25.9%), headache (13.4%), hypertension (11.2%), and sinusitis (10.4%). Expressed as incidence per 100 patient-years (nausea, 16.8%; headache, 8.7%; hypertension, 7.3%; and sinusitis, 6.8%), these rates were not inconsistent with product labeling. Serious TEAEs occurred in 8.9% of patients. Mean changes from baseline in systolic and diastolic blood pressure (supine SBP and DBP, respectively) were +4.0 and +3.3 mm Hg, respectively. Mean change from baseline in supine heart rate was +5 bpm and in body weight was -0.3 kg. Potentially clinically significant (PCS) increases in supine SBP (>=180 mm Hg and increase >=20 mm Hg) and DBP (>=110 mm Hg and increase >=15 mm Hg) were observed in 0.3% and 1.1% of patients, respectively; PCS increases in supine heart rate (>=120 bpm and increase >=20) were observed in 0.4% of patients. PCS increases and decreases in weight (>=7% change) were observed in 13.3% and 18.5% of patients, respectively.
Milnacipran, at doses of 50 to 200 mg/day, was generally well-tolerated and safe for periods of up to 3.25 years. No new safety concerns were identified in this long-term study.
To cite this abstract, please use the following information:
Arnold, Lesley M., Ma, Yimin, Palmer, Robert H., Spera, Allan, Baldecchi, Arlene; Safety and Tolerability of Milnacipran in a 3-Year, Open-Label, Flexible-Dosing Study of Patients with Fibromyalgia. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1905