Dimethyl fumarate reduces the risk of a first clinical event in RIS

A randomised, 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). Dimethyl fumarate reduced this risk by over 80%, the ARISE trial showed.

The randomised, double-blinded, placebo-controlled ARISE trial (NCT02739542) studied the use of dimethyl fumarate in people with RIS treated in 12 centres in the USA [1]. A total of 87 adult RIS patients were recruited and randomised 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 studied were the differences in the number of new or newly-enlarging T2 lesions, change in T2-lesion volume, and the number of gadolinium-enhancing (Gd+) lesions over 96 weeks. Prof. Darin Okuda (University of Texas Southwestern Medical Center, TX, USA) stressed that 10 out of 87 participants did not complete the full 96 weeks, as the study was prematurely terminated due to slow recruitment.

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 Gd+ lesions at baseline. This finding is highly consistent with the primary analysis results. MRI outcomes showed a significant reduction in the occurrence of new or newly-enlarging T2 lesions and in change in T2-lesion volume in the dimethyl fumarate group (see Figure).

Figure: Pre-specified secondary MRI outcomes [1]



Regarding 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.

1. Okuda D, et al. Multi-center, randomized, double-blinded assessment of DMF in extending the time to a first clinical demyelinating event in radiologically isolated syndrome (ARISE). Abstract O179, ECTRIMS 2022, 26–28 October, Amsterdam, the Netherlands.

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Posted on 20 December, 2022