Relapses Requiring Intravenous Steroid Use and Multiple Sclerosis (MS)-Related Hospitalizations: An Integrated Analysis of the BG-12 (Dimethyl Fumarate) Phase 3 Studies (P07.121)

OBJECTIVE: To report the effects of BG-12 (dimethyl fumarate) on number of relapses requiring intravenous (IV) steroids and MS-related hospitalizations, from a pre-specified integrated analysis of DEFINE and CONFIRM designed to estimate more precisely the therapeutic effect of dimethyl fumarate versus placebo. BACKGROUND: MS relapses treated with IV steroids are often those which are more severe and have significant impact on functional ability. In the Phase 3 DEFINE and CONFIRM studies, dimethyl fumarate significantly reduced relapses over 2 years versus placebo. DESIGN/METHODS: Patients aged 18–55 years with relapsing–remitting MS (McDonald criteria) and an Expanded Disability Status Scale score of 0–5.0 were recruited to both studies. Patients who received oral dimethyl fumarate 240 mg twice (BID) or three times daily (TID) or placebo were included in the integrated analysis, which was to be conducted only if baseline characteristics and treatment effects were homogeneous across the studies. Numbers of relapses requiring IV steroids and MS-related hospitalizations were tertiary endpoints in DEFINE and CONFIRM. RESULTS: The integrated analysis included 769, 761, and 771 patients who received dimethyl fumarate BID, TID, and placebo, respectively. There were significantly fewer relapses requiring steroids and MS-related hospitalizations in both dimethyl fumarate groups, versus placebo. At 2 years, dimethyl fumarate reduced the annualized rate of relapses requiring IV steroids by 48% (BID; rate ratio, 0.52 [95% confidence interval, 0.43–0.64]) and 50% (TID; 0.50 [0.41–0.61]) versus placebo (both p CONCLUSIONS: Dimethyl fumarate significantly reduced the number of relapses requiring IV steroids and MS-related hospitalizations, suggesting potential benefits in terms of reduced patient burden and health economic savings due to decreased resource utilization. These findings further support the efficacy results of DEFINE and CONFIRM. Supported by: Biogen Idec Inc. Disclosure: Dr. Giovannoni has received personal compensation for activities with Merck Serono, Biogen Idec, Vertex Pharmaceuticals, Bayer Schering Pharma, Pfizer Inc, Teva Pharmaceutical Industries Ltd, and Sanofi. Dr. Giovannoni has received research support from Biogen Idec, Merck Serono, Novartis, and Ironwood. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Gold has received personal compensation in an editorial capacity for Therapeutic Advances in Neurological Disorders. Dr. Gold has received a license fee from Biogen Idec. Dr. Gold has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Fox has received personal compensation for activities with Avanir, Biogen Idec, EMD Serono, and Novartis. Dr. Fox has received research support from Biogen Idec and Genentech. Dr. Kappos has receied personal compensation for activities with Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA and GlaxoSmithKline. Dr. Kappos has received research support from has received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim, Eisai, Elan, Genmab, GlaxoSmithKline, Glenmark, Merck Serono, MediciNova and Nova. Dr. Kita has received personal compensation for activities with Biogen Idec. Dr. Kita has received research support from Biogen Idec. Ms. Yang has received personal compensation for activities with Biogen Idec as an employee. Ms. Yang holds stock and/or stock options in Biogen Idec. Ms. Yang has received research support in Biogen Idec. Dr. Zhang has received personal compensation for activities with Biogen Idec Inc. as an employee. Dr. Zhang holds stock and/or stock options in Biogen Idec. Dr. Zhang has received research support from Biogen Idec. Dr. Dawson has received personal compensation for activities with Biogen Idec as an employee. Dr. Dawson holds stock and/or stock options in Biogen Idec. Dr. Dawson has received research support from Biogen Idec. Dr. Viglietta has received personal compensation for activities with Biogen Idec as an employee. Dr. Viglietta has received research support from Biogen Idec. Dr. Sheikh has received personal compensation for activities with Biogen Idec as an employee. Dr. Sheikh has received research support from Biogen Idec. Dr. Havrodova has received personal compensation for activities with Bayer, Biogen Idec, Genzyme Corporation, GlaxoSmithKline, Inc., Novartis, Merck & Co., Inc., Sanofi-Aventis Pharmaceuticals, Inc., Serono, and Teva Neuroscience.