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.
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Switch Study to Evaluate the Safety, Tolerability, and Efficacy of Milnacipran in Patients with An Inadequate Response to Duloxetine for the Treatment of Fibromyalgia.
Bateman1, Lucinda, Spera2, Allan, Palmer2, Robert H., Trugman2, Joel M., Lin2, Jennifer
As fibromyalgia (FM) treatments often do not have the same effectiveness in all FM patients; it is frequently necessary to switch therapies to achieve greater benefit or to avoid side effects. This study evaluates the safety, tolerability, and efficacy of milnacipran (MLN) following a direct switch from duloxetine (DLX) in FM patients with inadequate response to DLX. Although both compounds are serotonin/norepinephrine reuptake inhibitors, their pharmacologic properties differ, which may result in different responses and adverse-effect profiles in some FM patients.
Patients with FM were eligible for this study if they were currently receiving a stable dosage of DLX (60 mg/d) for >=4 weeks at screening. After 2 weeks of open-label treatment with DLX 60 mg/d, patients with VAS pain scores >=40 (range, 0100 mm) and dissatisfied with DLX were randomized 4:1 to receive MLN 100 mg/d (n=86) or placebo (PBO, n=21) for 10 weeks. The purpose of the small PBO group was to minimize expectation bias rather than provide a comparator arm, since patients would be discontinuing a treatment that may have been partially efficacious. In keeping with anecdotal clinical practice, patients randomized to the MLN group were directly switched from DLX to MLN with no tapering or titration periods. MLN dosage could be adjusted if necessary (required to be >=100 mg/d by Week 5). The primary efficacy parameter was the percentage of patients who rated themselves "much improved" or "very much improved" on the Patient Global Impression of Change (PGIC) scale. The secondary efficacy parameter was 1-week recall VAS pain score. Efficacy parameters were analyzed by using last observation carried forward.
Among patients switched from DLX to MLN, 59.3% completed the double-blind treatment period, and 17.4% discontinued due to adverse events (AEs) (in patients switched to PBO, 52.4% completed the double-blind period and 9.5% discontinued due to AEs). At Week 10, 32.9% of patients switched from DLX to MLN were PGIC responders and the overall MLN group had a mean decrease from baseline in VAS pain of 12.3 mm (in the group switched to PBO, 23.8% of patients qualified as PGIC responders, but the mean decrease from baseline in VAS pain was only 1.3 mm). 34.2% of patients switched from DLX to MLN showed >=30% improvement in VAS pain, whereas 29.1% of patients had >=40% improvement, and 25.3% had >=50% improvement. Treatment-emergent AEs in patients switched to MLN were similar to those reported in previous PBO-controlled trials. The most common TEAEs in those patients were nausea (21% of patients switched to MLN and 29% in patients switched to PBO) and dizziness (15% MLN, 5% PBO). For comparison, in previous studies conducted in patients not switching from another SNRI, at a dosage of MLN 100 mg/d, the incidence of nausea was 35% and dizziness was 11% (Savella package insert). There were 2 SAEs among patients switched from DLX to MLN: suicidal ideation and hypersensitivity.
These results suggest that FM patients with an inadequate response to DLX treatment may benefit from a switch to MLN for management of their symptoms. Additionally, a direct switch from DLX to MLN was safe and well tolerated in this study.
To cite this abstract, please use the following information:
Bateman, Lucinda, Spera, Allan, Palmer, Robert H., Trugman, Joel M., Lin, Jennifer; A Multicenter, Randomized, Double-Blind, Placebo-Controlled Switch Study to Evaluate the Safety, Tolerability, and Efficacy of Milnacipran in Patients with An Inadequate Response to Duloxetine for the Treatment of Fibromyalgia. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1609