Abstract: Gastrointestinal Tolerability Events with BG-12 (Dimethyl Fumarate) in MS (The 27th Annual Meeting of the CMSC and the 5th Cooperative Meeting of the CMSC-ACTRIMS)

Friday, May 31, 2013: 1:40 PM

Lake Lucerne AB

Krzysztof Selmaj, MD, PhD , Medical University of Lodz, Lodz, Poland, Lodz, Poland

Ralf Gold, MD , St Josef Hospital, Ruhr University, Bochum, Germany, Bochum, Germany

Robert J. Fox, MD, FAAN , Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic, Cleveland, OH

Eva Havrdova, MD, PhD , Department of Neurology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic, Prague, Czech Republic

Gavin Giovannoni, PhD , Queen Mary University of London, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK, London, United Kingdom

Amy Pace, ScD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

Mark Novas, MD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

Leslie Meltzer, PhD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

Christophe Hotermans, MD, PhD , Biogen Idec Inc., Weston, MA, USA, Weston, MA

Katherine T. Dawson, MD , Biogen Idec Inc., Weston, MA, USA, Cambridge, MA

J. Theodore Phillips, MD PhD FAAN , Multiple Sclerosis Program, Baylor Institute for Immunology Research, Dallas, TX, USA, Dallas, TX

Background: BG-12 (dimethyl fumarate) demonstrated an acceptable safety profile in Phase 3 studies. Common adverse events (AEs) associated with BG-12 included flushing and gastrointestinal (GI) events. Most patients reported GI events that were mild/moderate in severity and decreased substantially in incidence after the first month of treatment.

Objectives: To characterize GI AEs in relapsing–remitting MS patients treated with BG-12 twice daily (BID) in a post-hoc analysis of integrated data from the Phase 3 DEFINE and CONFIRM studies.

Methods: Incidence, nature, severity, and management of GI AEs (by manual review of indications of concomitant medications and timing vs AEs) were summarized for patients treated with BG-12 240 mg BID versus placebo in DEFINE and CONFIRM, focusing on Months 0–3 (when GI AE incidence was highest).

Results: A total of 769 patients received BG-12 and 771 received placebo with 70% and 65% completing 2 years of treatment, respectively. GI AEs were reported by 40% versus 31% patients overall, and 41% versus 34% patients who completed 2-year treatment (sensitivity analysis) in BG-12 and placebo groups, respectively. In Months 0–3, the incidence of GI AEs was 27% versus 17% in BG-12 and placebo groups, respectively. 3% versus <1% patients discontinued treatment due to GI AEs, and 11% versus 4% had GI AEs that required symptomatic therapy, respectively. Within the first 3 months of BG-12 treatment, the most common (≥5% patients) events were nausea, diarrhea, abdominal pain (upper or unspecified), and vomiting. Of the abdominal/upper abdominal pain, nausea/vomiting, and diarrhea events, 91%, 95%, 96% were mild/moderate, 7%, 12%, 6% resulted in treatment discontinuation, 93%, 95%, 96% resolved (median duration 9.5 days, 8 days, 8 days), and 38%, 33%, 26% utilized symptomatic therapy, respectively. Common symptomatic therapies for abdominal/upper abdominal pain were omeprazole, paracetamol, ranitidine; nausea/vomiting were metoclopramide, domperidone; and diarrhea was loperamide (efficacy not assessed).

Conclusions: The incidence of GI AEs was highest in the first 3 months of treatment. Most events were mild-to-moderate in severity and resolved after a median duration of less than 2 weeks while few GI events resulted in treatment discontinuation. Further studies are needed to evaluate the efficacy of individual management strategies.

SX03 Gastrointestinal Tolerability Events with BG-12 (Dimethyl Fumarate) in MS