Gastrointestinal Tolerability of Delayed-Release Dimethyl Fumarate in Relapsing Multiple Sclerosis: A Multicenter, Open-Label Study

Thursday, May 29, 2014
Trinity Exhibit Hall
Edward J Fox, MD, PhD , Central Texas Neurology Consultants, University of Texas Medical Branch, Round Rock, TX
Alberto Vasquez, MD , Suncoast Neuroscience Associates, St. Petersburg, FL
William Grainger, MD , Neurological Physicians of Arizona, Gilbert, AZ
Tina S Ma, PhD , Department of Biostatistics, PharmStats, Ltd., Escondido, CA
Jie Li, MD , Biogen Idec, Inc., Cambridge, MA
Javier Zambrano, MD , Biogen Idec, Inc., Weston, MA

Background: Delayed-release dimethyl fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting MS (RRMS) in the 2-year, Phase 3 DEFINE and CONFIRM studies. Common adverse events associated with delayed-release DMF included flushing and gastrointestinal (GI)-related events such as nausea, diarrhea, and abdominal pain.

Objectives: To evaluate the effect of symptomatic therapies on GI-related events in adult patients with relapsing forms of MS initiating delayed-release DMF therapy in clinical practice in the United States, in the 12-week, multicenter, open-label MANAGE study.

Methods: Patients were treated with delayed-release DMF, taken with or within 1 hour after a meal, at 120mg twice daily (BID) for 7 days and 240mg BID thereafter. The primary endpoint is the frequency, severity, and duration of GI-related events. Secondary endpoints include the cumulative proportion of patients requiring symptomatic therapy; the type, frequency, and duration of symptomatic therapies; and discontinuation rates due to events requiring symptomatic therapy.

Results: MANAGE enrolled 237 patients with a mean age of 47 years (range: 18.0−74.0) and mean duration of MS of 9.5 years (range: 0.0−42.0). Among them, 184 (77.6%) were female and 219 (92.4%) were Caucasian. Patients’ mean baseline EDSS score was 2.6 (range: 0.0−7.5) and mean number of relapses within the previous 1, 2, and 3 years were 0.7 (range: 0−16), 1.1 (0−31), and 1.6 (0−47), respectively. MANAGE is ongoing; results will be reported.

Conclusions: MANAGE is a 12-week, multicenter, open-label study evaluating the effect of symptomatic therapies on GI-related events in relapsing MS patients initiating delayed-release DMF therapy.