Late Breaking NewsSaturday, October 05, 2013, 08:54 - 09:06
A phase II trial of neuroprotection with riluzole in early relapsing-remitting MSE. Waubant, A.H. Maghzi, N. Revirajan, R. Spain, L. Julian, E. Mowry, S. Liu, C. Jin, A.J. Green, C.E. McCulloch, D. Pelletier (San Francisco, Portland, Baltimore, New Haven, US)
Background: Approved MS drugs have limited neuroprotective benefit.
Aims: To determine the effect of riluzole 50 mg bid versus placebo added to weekly interferon beta-1a in early RRMS.
Methods: This is a randomized, double-blind, placebo-controlled (1:1) trial of riluzole 50 mg bid in subjects with MS onset within the prior year. Trial participation was up to three years. The primary endpoint was change in brain volume (SIENA). Secondary endpoints included grey and white matter atrophy (SIENAX) and changes in MS functional composite (MSFC), peripapillary retinal nerve fiber layer thickness (RNFL), and Symbol Digit Modality Test (SDMT). Mixed model regression analysis was used to compare the changes over time between groups, while accounting for longitudinal data.
Results: 43 subjects were randomized (22 riluzole, 21 placebo) within a mean of 7.5 months of disease onset (median age 34.3 years, 72.1% females, median EDSS 2.0, 30.2% with enhancing scans). Baseline characteristics were similar between groups except for older age (p=0.042), higher normalized CSF volume (p=0.050) and lower normalized grey matter volume (nGMV) (p=0.14) in riluzole subjects. Normalized lesion volume was 7.56 ± in the riluzole group compared with 4.01 ± 4.67 in the placebo group (p=0.21). In the primary analysis, brain volume (SIENA) in the placebo group decreased at a rate of 0.49% per year whereas the active group decreased at a rate of 0.86%, a greater decline (0.37% more per year; p 0.065). Although age did not seem to influence the rate of brain volume decline, the difference between treatment groups decreased when analyses were adjusted for baseline nGMV and baseline normalized lesion volume (0.26% more per year; p=0.22) as pre-planned. Secondary analyses showed no group differences for changes in nGMV, nWMV, MSFC, RNFL and SDMT (p> 0.36). Riluzole subjects developed more new T2 lesions than placebo during the study (p=0.047).
Conclusions: Riluzole does not reduce brain atrophy progression in early RRMS (class 1 evidence).
Dr. Waubant has received honorarium from Roche, Sanofi Aventis and Genentech for three educational lectures, and is on the advisory board for a trial of Novartis. Dr. Waubant has received free medication from Biogen Idec and Sanofi-Aventis for this trial. This research was performed as a research grant funded by the National MS Society (PI Waubant, RG 3932-A-2). Sanofi Aventis and Biogen Idec provided free riluzole and placebo, and interferon beta-1a. E.W. is also supported by the Nancy Davis Foundation, the National MS Society and the NIH (R01NS071463 - 01). A.H.M. is supported by the International MS Federation through a McDonald fellowship. Dr. Pelletier has received consulting fees from CNS Imaging Consultant, LLC, and research grants to his academic institution from Hoffmann-LaRoche, Biogen-Idec, and Genzyme.