Sustained Low Rate of Brain Volume Loss under Long-term Delayed-Release Dimethyl Fumarate Treatment in Relapsing-Remitting Multiple Sclerosis Patients: Results from the ENDORSE Study (P7.243)

OBJECTIVE: Evaluate the long-term effect on brain volume loss in patients receiving continuous delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) treatment compared with patients switching from placebo or glatiramer acetate (GA) in ENDORSE, an extension of the phase 3 DEFINE and CONFIRM studies.BACKGROUND: Brain atrophy in MS has been shown to correlate with physical disability, cognitive deficits, and quality of life.DESIGN/METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or three times (TID) daily in DEFINE/CONFIRM continued the same dosage. Patients randomized to placebo (PBO) or GA (CONFIRM only) were re-randomized 1:1 to DMF BID or TID. Data were analyzed (May 14, 2014 cutoff) by treatment in parent/extension study; we report BID data, as this represents the approved dose. At year 3 (week 144) of ENDORSE, BID/BID patients received 蠅5 years continuous DMF treatment; PBO/BID and GA/BID patients received 2 years PBO (DEFINE/CONFIRM) or GA (CONFIRM), respectively, followed by 蠅3 years DMF (ENDORSE). Percentage brain volume change (PBVC) was calculated at year 3 of ENDORSE relative to the predefined baseline for PBVC, week 24 of DEFINE/CONFIRM.RESULTS: This analysis was conducted in the MRI cohort of ENDORSE. Normalized brain volume data was available for 195 (BID/BID), 87 (PBO/BID), and 42 (GA/BID) patients. Mean PBVC at year 3 (over 218 weeks or 4.5 years) of ENDORSE relative to week 24 of DEFINE/CONFIRM was 1.38 (BID/BID), 1.90 (PBO/BID), and 2.05 (GA/BID). In the BID/BID group, the rate of brain volume loss was slowed compared with placebo (P=0.0304) and significantly slowed across all time points compared with PBO/BID and GA/BID.CONCLUSIONS: This analysis suggests a continuous beneficial effect of DMF on brain atrophy and a higher impact of early compared with delayed DMF treatment.Study Supported by: Biogen Idec Disclosure: Dr. Kappos has received personal compensation for activities with Actelion Pharmaceuticals. Dr. Fox has received personal compensation for activities with Biogen Idec, GlaxoSmithKline, Inc., Novartis, Questcor, Teva, and Xenoport. Dr. Fox has received research support from Novartis. Dr. Gold has received personal compensation for activities with Bayer HealthCare, Biogen Idec, Merck Serono, Novartis, and Teva Neuroscience. Dr. Arnold has received personal compensation for activities with Acorda, Bayer Healthcare, Biogen Idec, Merck Serono, Genentech, Genzyme, GlaxoSmithKline, Medimmune, Novartis, Receptos, Inc., Roche, Sanofi-Aventis, and Teva. Dr. Potts has received personal compensation for activities with Biogen Idec as an employee. Dr. Zhang has received personal compensation for activities with Biogen Idec as an employee. Dr. Kurukulasuriya has received personal compensation for activities with Biogen Idec as an employee.