Breaking Bad...........News from ECTRIMS

E. Waubant et al.  A phase II trial of neuroprotection with riluzole in early relapsing-remitting MS. Ectrims late breaking news

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). 

This more bad news for people with progressive MS and looks like Neuros are flushing another treatment away. What does this say well it says that riluzole a sodium channel blocker and glutamate receptor blocker does not work in early MS. Therefore is the writing on the wall for this class of drugs so is PROXIMUS doomed? Has MS-SMART made a bad choice because they are going to test riluzole on progressive MS. Well if MRI is the main outcome and it is looking at brain atrophy then maybe so. Just as has happened with the lamotrigine trial the drug appears to be making the brain shrink quicker than placebo. So is it killing nerves, maybe not. It is probably anti-inflammatory and getting rid of swelling so making the brain appear to shrink. So another drug failing with perhaps an inapprorpriate trial design/outcome measure. 

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