Abstract Details

Title Effects of Dimethyl Fumarate on Brain Volume Change in Relapsing-remitting Multiple Sclerosis: a Pooled Analysis of the Phase 3 DEFINE and CONFIRM Studies

Topic Multiple Sclerosis

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-064

Objective To evaluate effects of dimethyl fumarate (DMF) on brain volume change in multiple sclerosis (MS) patients through re-analysis of pooled images from DEFINE/CONFIRM trials.

Background In original analyses, patterns of brain volume changes were different between DEFINE/CONFIRM, potentially due to low sample sizes and because MRIs were analyzed at two different reading centers. Therefore, MRIs were pooled and reanalyzed at a single center to re-assess brain volume loss.

Design/Methods MRIs from DEFINE/CONFIRM at Weeks 0, 24, 48, and 96 from patients randomized to DMF twice-daily (DMF) or placebo (PBO) were reanalyzed at the Cleveland Clinic to measure brain parenchymal fraction (BPF). Percent change in BPF at Weeks 0–48 and Weeks 48–96 were calculated. Additionally, a repeated measures model assessed BPF change for Weeks 0-48 and for 48-96 using all available BPF data, from which the treatment effect was calculated.

Results Across studies, 301 DMF and 314 PBO patients had analyzable MRIs. In Weeks 0-48, mean (±standard error [SE]) percentage change in BPF was -0.44±0.04 vs -0.34±0.04, in DMF vs PBO, respectively, whereas in Weeks 48-96, mean ±SE percentage change in BPF was -0.27±0.03 vs -0.41±0.04, in DMF vs PBO, respectively. The repeated measures mixed model showed similar results: Weeks 0-48, least-squares mean (95% CI) change in BPF was -0.0031 (-0.0037, -0.0024) DMF vs -0.0023 (-0.0030, -0.0017) PBO, whereas in Weeks 48-96 the estimated change in BPF was -0.0021 (-0.0027, -0.0016) DMF vs -0.0033 (-0.0039, -0.0028) PBO (a 35.9% reduction; P = 0.0025).

Conclusions Consistent with demonstrated effects of DMF on relapses, disability, and lesions, pooled BPF analysis showed that DMF slowed rate of whole brain volume loss in the second year compared with PBO (35.9%). Brain volume changes in the first year were consistent with pseudoatrophy effects observed in other MS clinical trials.

Supported by: Biogen

Authors/Disclosures
Kunio Nakamura, PhD (Cleveland Clinic) PRESENTER	Dr. Nakamura has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for INmune Bio. The institution of Dr. Nakamura has received research support from Biogen. The institution of Dr. Nakamura has received research support from PCORI. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from NIH. The institution of Dr. Nakamura has received research support from Genzyme. The institution of Dr. Nakamura has received research support from Novartis. The institution of Dr. Nakamura has received research support from DOD. Dr. Nakamura has received intellectual property interests from a discovery or technology relating to health care.
	No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
	No disclosure on file
Ludwig Kappos, MD, FAAN (RC2NB, University Hospital Basel)	Dr. Kappos has nothing to disclose.
Nancy D. Richert, MD, PhD (Research Imaging LLC)	No disclosure on file
Elizabeth Fisher	Elizabeth Fisher has received personal compensation for serving as an employee of Biogen. Elizabeth Fisher has stock in Biogen. Elizabeth Fisher has received intellectual property interests from a discovery or technology relating to health care.
Sarah Gheuens, MD	No disclosure on file

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