OBJECTIVE: To characterize the temporal profile of BG-12 (dimethyl fumarate) treatment efficacy in an integrated analysis of data from the Phase 3 DEFINE and CONFIRM studies.
#MSBlog: BG12 works within 12 weeks of starting treatment.
Kappos et al. Timecourse of Treatment Effects of BG-12 (Dimethyl Fumarate) for Relapsing–Remitting Multiple Sclerosis. AAN 2013; S41.005.
BACKGROUND: Oral dimethyl fumarate has demonstrated significant reductions in relapses and brain magnetic resonance imaging (MRI) activity over 2 years in patients with relapsing–remitting multiple sclerosis (RRMS) in DEFINE and CONFIRM.
DESIGN/METHODS: MSers with RRMS were randomized equally to oral dimethyl fumarate 240 mg twice (BID) or three times daily (TID) or placebo in both studies. CONFIRM also included glatiramer acetate as reference comparator. Primary endpoints were proportion of MSers relapsed (DEFINE) and annualized relapse rate (ARR; CONFIRM). MRI was performed at baseline and Weeks 24, 48 and 96, in a subset of MSers. The integrated analysis was contingent upon homogeneous baseline characteristics and treatment effects across the studies.
RESULTS: The intent-to-treat population for the integrated analysis comprised 769, 761 and 771 MSers assigned to dimethyl fumarate BID, TID and placebo, respectively. Dimethyl fumarate treatment reduced the proportion of patients relapsed and ARR, with significant separation versus placebo achieved at Week 12 (post-hoc analyses); the hazard ratio (and 95% confidence interval [CI]) for risk of relapse at Week 12 was 0.68 (0.48, 0.96) for the BID group (p=0.0282) and 0.70 (0.50, 0.99) in the TID group (p=0.046), and the rate ratio (95% CI) for ARR was 0.66 (0.47, 0.92) (BID; p=0.0149) and 0.69 (0.49, 0.96) (TID; p=0.0299). Significant separation was maintained thereafter; by 2 years, dimethyl fumarate BID and TID reduced the risk of relapse by 43% and 47% versus placebo, and ARR by 49% for both, (all p<0.0001). MRI outcomes were consistent with the time course of clinical effect.
CONCLUSIONS: Dimethyl fumarate treatment resulted in significant improvements in disease activity over placebo that were apparent by 3 months, and sustained over 2 years.
Supported by: Biogen Idec Inc.
“In response to a question yesterday about the onset of action of BG12; according to this analysis the curves go apart very soon after starting the drug and are signficant by 12 weeks. This suggests to me that BG12 is probably working as an anti-inflammatory drug.”
“Does this answer your question?”