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Dimethyl Fumarate Delays Clinical Conversion to Multiple Sclerosis in Radiologically Isolated Syndrome

Dimethyl fumarate in RIS delays clinical conversion to MS.

The need for early treatment initiation in multiple sclerosis (MS) is well known. However, until recently, there was no approved disease modifying therapy (DMT) in radiologically isolated syndrome (RIS).

Okuda et al. [1] have performed a multi-center, randomized, double-blinded, placebo-controlled study evaluating the impact of dimethyl fumarate (DMF) in people with RIS. Participants from 12 MS centres in the United States were randomly assigned 1:1 to oral DMF 240 mg twice daily or placebo (44 were randomized to DMF and 43 to placebo).  The primary endpoint was the time to onset of clinical symptoms attributable to a central nervous system demyelinating event within a follow-up period of 96 weeks. The main results were as follows:

  1. Following DMF treatment, the risk of an initial clinical demyelinating event during the 96-week period was significantly reduced in the unadjusted Cox proportional-hazards regression model (HR=0.18, 95% CI=0.05-0.63, p=0.007).
  2. The DMF-treated participants showed a reduced cumulative number of new and/or newly-enlarging T2-weighted hyperintense brain lesions compared to placebo. (0.12 versus 0.62, rate ratio=0.20, 95% CI=0.04-0.94, p=0.042). Notably, the presence of spinal cord lesions was not determined.
  3. Moderate adverse reactions were more frequent in the DMF group (32%) than in the placebo group (21%). However, severe adverse events were similar (5% and 9%, respectively).

This is the first randomized clinical trial to demonstrate the benefit of a DMT in delaying MS clinical onset.

Key Points:

  • In people with RIS, treatment with DMF delays clinical conversion to MS, underlying the importance of early therapeutic intervention.
  • Treatment with DMF reduced the brain lesional charge in people with RIS.
  • Correct assessment of RIS, both clinically and radiologically, is essential.


  1. Okuda D. T., Kantarci O., Lebrun-Frénay C. et al. Dimethyl fumarate delays multiple sclerosis in radiologically isolated syndrome. Ann Neurol. 2023. 93(3): 604-614. doi: 10.1002/ana.26555. pubmed.ncbi.nlm.nih.gov/36401339/

Publish on behalf of the Scientific Panel on Multiple sclerosis