Rate of Brain Volume Loss with Long-Term Delayed-Release Dimethyl Fumarate Treatment in Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Results from ENDORSE (P3.061)

Objective: Evaluate the long-term rate of brain volume loss (BVL) in patients receiving continuous delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) treatment versus those switching from placebo (PBO). Background: DMF demonstrated robust efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis in the DEFINE, CONFIRM, and ENDORSE studies. Methods: In the ENDORSE extension study, patients randomized to DMF 240 mg twice (BID) or thrice (TID) daily in DEFINE/CONFIRM continued the same dosage. PBO or glatiramer acetate (CONFIRM only) patients were re-randomized 1:1 to DMF BID or TID. Percentage brain volume change (PBVC) was calculated using the SIENA method for each MRI visit relative to baseline. BID data (approved dosage) are reported for patients continuously treated with DMF. BID and TID data were pooled for patients switching from PBO to increase sample size; Years 3-6 (ENDORSE) represent 4 years of DMF after switching. Analyses included only patients with yearly PBVC data from ENDORSE. Results: Among the DEFINE/CONFIRM MRI cohort patients who participated in ENDORSE (n=211 [BID/BID] and 206 [PBO/DMF]), 87 BID/BID and 70 PBO/DMF patients had yearly PBVC data. Using rank analysis, adjusted PBVC at Year 2 relative to DEFINE/CONFIRM baseline was significantly lower with DMF BID (median -0.5) versus PBO (median -0.79; P=0.0110). After 4 years of DMF treatment, PBVC was not significantly different for PBO/DMF versus BID/BID, relative to ENDORSE baseline. In BID/BID patients, a low annualized PBVC was observed over 6 years (mean [95[percnt] confidence interval]: -0.34/year [-0.39, -0.29]). Conclusions: In DEFINE/CONFIRM, patients treated with DMF BID had significantly reduced BVL over 2 years versus PBO. Over 6 years, annual rates of BVL in patients treated continuously with DMF were low and approached rates reported for healthy volunteers, consistent with a sustained beneficial effect of DMF on brain atrophy. Study supported by: Biogen. Disclosure: Dr. Kappos9s institution (University Hospital Basel) has received royalty payments from Neurostatus Systems GmbH. Dr. Yousry has received research support from Biogen Idec, British Heart Foundation, GlaxoSmithKline, Medical Research Council, MS Society of Great Britain and Northern Ireland, and NIHR Comprehensive. Dr. Fox has received personal compensation for activities with Actelion, Biogen Idec, MedDay, Novartis, Questcor, Teva, and Xenoport as a consultant; served on advisory committees for Actelion, Biogen Idec and Novartis. Dr. Fox has received research suppo Dr. Gold has received research support from Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Arnold holds stock and/or stock options in NeuroRx Research, which sponsored research in which Dr. Arnold was an investigator. Dr. Potts has received personal compensation for activities with Biogen Idec as an employee. Dr. Marantz holds stock and/or stock options in Biogen.