For the first time, a randomized, placebo-controlled trial demonstrated beneficial effects of a disease-modifying therapy (DMT) in preventing a first acute clinical event in people with a radiologically isolated syndrome (RIS). In the ARISE trial, dimethyl fumarate reduced this risk by over 80%.
The randomized, double-blinded, placebo-controlled ARISE trial (NCT02739542) studied the use of dimethyl fumarate in people with RIS treated in 12 USA centers. Between March 2016 and October 2019, 87 adult RIS patients were recruited and randomized 1:1 to oral dimethyl fumarate, 240 mg, twice daily or placebo. The primary endpoint was the time to onset of clinical symptoms attributable to a CNS demyelinating event at week 96. Also examined were the differences in the number of new or newly enlarging T2-lesions, change in T2-lesion volume, and the number of gadolinium-enhancing (Gad+) lesions over 96 weeks. Prof. Darin Okuda (University of Texas Southwestern Medical Center, TX, USA) stressed that 10/87 participants did not complete the full 96 weeks, as the study was prematurely terminated due to slow recruitment. He pointed out that if these 10 people were excluded, the discontinuation rate would be a mere 20%.
The risk of a first clinical demyelinating event was reduced in the dimethyl fumarate group in the unadjusted Cox proportional-hazards regression model (HR 0.18; 95% CI 0.05–0.63; P= 0.007) and in the adjusted analysis (HR 0.07; 95% CI 0.01–0.45; P=0.005). The pre-specified Bayesian analysis revealed a significant reduction in the number of new or newly enlarging, T2-weighted, hyperintense lesions in the dimethyl fumarate arm compared with placebo (HR=0.20; 95% CI 0.04–0.94; P=0.042) after adjusting for the number of Gad+ lesions at baseline. This finding is very consistent with the primary analysis results.
Concerning safety, there were more moderate adverse events in the dimethyl fumarate group (34; 32%) than in the placebo group (19; 21%). However, severe events were similar with 3 (5%) in the dimethyl fumarate group and 4 (9%) in the placebo group.
“This data supports the benefit of early intervention in the MS disease spectrum,” concluded Prof. Okuda.
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