OBJECTIVES: To report the effect of BG-12 (dimethyl fumarate) in reducing the number of relapses requiring intravenous (IV) steroids and multiple sclerosis (MS)-related hospitalizations from a pre-specified integrated analysis of DEFINE and CONFIRM, which was designed to estimate–more precisely–the therapeutic effect of BG-12 versus placebo. METHODS: Eligible patients were aged 18–55 years with relapsing–remitting MS (McDonald criteria) and an Expanded Disability Status Scale score of 0–5.0. Patients who received oral BG-12 240 mg twice (BID) or three times daily (TID) or placebo were included and the integrated analysis was to be conducted only if baseline characteristics and treatment effects were similar between the studies. Numbers of relapses requiring IV steroids and MS-related hospitalizations (tertiary endpoints in DEFINE and CONFIRM) were assessed. RESULTS: The integrated analysis included 769, 761, and 771 patients who received BG-12 BID, TID, and placebo, respectively. Baseline characteristics and treatment effects were generally similar between DEFINE and CONFIRM. There were significantly fewer relapses requiring steroids and MS-related hospitalizations in both BG-12 groups compared with placebo. BG-12 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<0.0001) and reduced the annualized rate of MS-related hospitalizations by 34% (BID; 0.66 [0.47–0.92]; p=0.0146) and 47% (TID; 0.53 [0.37–0.75]; p=0.0004) at 2 years. CONCLUSIONS: BG-12 significantly reduced the number of relapses requiring IV steroids and MS-related hospitalizations, which suggests benefits with regard to patient burden and health economic savings due to decreased resource utilization. These findings further support the efficacy results of DEFINE and CONFIRM.