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Journal of Neurology

, Volume 261, Issue 9, pp 1794–1802

First Online: 03 July 2014Received: 13 February 2014Revised: 09 June 2014Accepted: 10 June 2014

Abstract

In the Phase 3 DEFINE study, delayed-release dimethyl fumarate DMF 240 mg twice BID and three times daily TID significantly reduced the mean number of new or enlarging T2-hyperintense lesions and gadolinium-enhancing Gd+ lesion activity at 2 years in patients MRI cohort; n = 540 with relapsing–remitting MS. The analyses described here expand on these results by considering additional MRI measures number of T1-hypointense lesions; volume of T2-hyperintense, Gd+, and T1-hypointense lesions; brain atrophy, delineating the time course of the effects, and examining the generality of the effects across a diverse patient population. Reductions in lesion counts with delayed-release DMF BID and TID, respectively, vs. placebo were apparent by the first MRI assessment at 6 months T2-hyperintense: 80 and 69 % reduction both P < 0.0001; Gd+, 94 and 81 % reduction both P < 0.0001; T1-hypointense: 58 % P < 0.0001 and 48 % P = 0.0005 reduction and maintained at 1 and 2 years. Reductions in lesion volume were statistically significant beginning at 6 months for T2-hyperintense P = 0.0002 BID and P = 0.0035 TID and Gd+ lesions P = 0.0059 BID and P = 0.0176 TID and beginning at 1 year P = 0.0126 BID to 2 years P = 0.0063 TID for T1-hypointense lesions. Relative reductions in brain atrophy from baseline to 2 years 21 % reduction; P = 0.0449 and 6 months to 2 years 30 % reduction; P = 0.0214 were statistically significant for delayed-release DMF BID. The effect of delayed-release DMF on mean number of new or enlarging T2-hyperintense lesions and Gd+ lesion activity was consistent across pre-specified patient subpopulations. Collectively, these results suggest that delayed-release DMF favorably affects multiple aspects of MS pathophysiology.

KeywordsBrain atrophy Delayed-release dimethyl fumarate Lesion MRI Relapsing–remitting multiple sclerosis For the DEFINE study investigators See online supplement, appendix e-1.

Electronic supplementary materialThe online version of this article doi:10.1007-s00415-014-7412-x contains supplementary material, which is available to authorized users.

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Autor: Douglas L. Arnold - Ralf Gold - Ludwig Kappos - Amit Bar-Or - Gavin Giovannoni - Krzysztof Selmaj - Minhua Yang - Ray Zha

Fuente: https://link.springer.com/



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