CMSC 2012: Dimethyl Fumarate Significantly Improves Number and Volume of Lesions on MRI in Relapsing-Remitting MS

SAN DIEGO — Treatment with the investigational oral treatment for relapsing-remitting multiple sclerosis (RRMS), dimethyl fumarate (also known as BG-12), yielded significant reductions in inflammatory disease activity using MRI outcomes, according to research presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Dimethyl fumarate, currently under review by US and European regulators as a monotherapy treatment for RRMS, is thought to have both anti-inflammatory and neuroprotective effects. Its efficacy was studied in the two phase 3 trials—the DEFINE and CONFIRM studies.

Douglas L. Arnold, MD, NeuroRx Research in Montreal, QC, Canada, and colleagues conducted a study involving 1,237 patients aged 18 to 55 years with RRMS and an Expanded Disability Status Scale (EDSS) score less than 5 who received either placebo, dimethyl fumarate 240 mg twice daily (BID), or 240 mg three times per day (TID) in the phase 3 DEFINE study. A representative subset of 540 patients from the DEFINE trial underwent magnetic resonance imaging (MRI) scans at baseline, 24 weeks, 1 year, and 2 years to evaluate the number and volume of T2-hyperintense, gadolinium-enhancing (Gd+), and nonenhancing T1-hypointensive lesions.

At 1 year, both BID and TID regimens of dimethyl fumarate yielded statistically significant benefits in all MRI outcomes compared with placebo, and these benefits were sustained at 2 years. Compared with placebo, dimethyl fumarate reduced the number of new or newly enlarging T2 lesions by 85% and 74% for the BID and TID regimens, respectively. The number of Gd+ lesions was also reduced by 90% and 73%, respectively, compared with placebo. Finally, the number of new nonenhancing T1-hypointense lesions was reduced by 72% and 63%, respectively.

Lesion volume was also significantly reduced with both dimethyl fumarate BID and TID treatment, compared with placebo. The median change from baseline in T2-hyperintense lesion volume was reduced by 6.2% for BID and 1.9% for TID, compared with an increase of 20.1 for placebo. Nonenhancing T1-hypointense lesions increased by 8%, 13%, and 27% for dimethyl fumarate BID, TID, and placebo, respectively. Gadolinium-enhancing lesion volume was reduced by 79% and 53% for dimethyl fumarate BID and TID treatment, respectively, compared with an increase of 106% in placebo-treated patients.

“Results of MRI analyses in the DEFINE study demonstrate significant reductions in inflammatory disease activity as measured by the number and volume of T2-hyperintense, nonenhancing T1-hypointense, and Gd+ lesions compared with placebo, further supporting its efficacy in RRMS,” the authors concluded.

This research was supported by Biogen Idec Inc.