OBJECTIVES: To report effects of BG-12 on the reduction in number of relapses requiring intravenous steroids and multiple sclerosis (MS)-related hospitalizations in DEFINE and CONFIRM, two Phase 3 studies of efficacy and safety of oral BG-12 (dimethyl fumarate) in patients with relapsing-remitting MS (RRMS). METHODS: Patients aged 18 -55 years with RRMS (McDonald criteria 2005) and an Expanded Disability Status Scale score of 0 -5.0 were randomized equally to oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo in DEFINE, or to oral BG-12 240 mg BID or TID, placebo, or subcutaneous glatiramer acetate 20 mg/day (reference comparator) in CONFIRM. The primary endpoint at 2 years was: the proportion of patients relapsed in DEFINE, and annualized relapse rate in CONFIRM. Tertiary endpoints in both studies included number of relapses requiring intravenous steroid therapy and MS-related hospitalizations. RESULTS: The intent-to-treat populations of the DEFINE and CONFIRM studies comprised 1,234 and 1,417 patients, respectively. In DEFINE, BG-12 reduced the adjusted annualized rate of relapses requiring steroids at 2 years by 52% (BID; rate ratio, 0.48 [95% confidence interval, 0.36 -0.63]) and 51% (TID; 0.49 [0.37-0.64]) vs placebo (both pϽ0.0001). Relative reductions in CONFIRM were 44% (BID; 0.56 [0.42-0.76]) and 49% (TID; 0.51 [0.38 -0.70]) vs placebo (pϭ0.0002 and pϽ0.0001). BG-12 also reduced the adjusted annualized rate of MS-related hospitalizations at 2 years in DEFINE by 35% (BID; 0.