Impact of Dimethyl Fumarate for Primary Progressive MS Unclear After Open-Label Extension

Up to 2 years of dimethyl fumarate treatment showed no clear effects on clinical or magnetic resonance imaging (MRI) outcomes, or changes in serum concentrations of neurofilament light chain, in patients with primary progressive multiple sclerosis (MS), according to study findings published in Multiple Sclerosis and Related Disorders.

“Dimethyl fumarate treatment is approved in Europe for patients with relapsing-remitting MS and in the United States for relapsing forms of MS,” wrote a research team from Denmark. “We recently published the results of the first randomized placebo-controlled trial of 48 weeks of treatment with dimethyl fumarate or placebo in primary progressive MS … The placebo-controlled phase of the trial did not meet its primary endpoint (reduction in cerebrospinal fluid concentrations of neurofilament light chain).”

The current study examined the impact of dimethyl fumarate in the open-label extension phase of the trial, during which all patients were treated with dimethyl fumarate from week 48 through week 96. 

Of 42 patients who entered the open-label extension phase, 39% did not finish. In the remaining 33 patients with data at week 96, researchers found no evidence of differences in clinical and MRI measures between patients initially treated with dimethyl fumarate and patients who switched from placebo to dimethyl fumarate for the open-label extension. Serum neurofilament light chain concentrations were stable in both groups over the 96 weeks of the trial, according to the study.

At week 96, 45% of patients showed disease progression on the Expanded Disability Status Scale, Timed 25-Foot Walk test, or 9-Hole Peg Test. Meanwhile, 46% improved in one or more of the tests. On the Symbol Digit Modalities Test, 6% of patients worsened, 78% had no change, and 16% showed improvement, authors of the study found.

“An expected number of patients showed evidence of progression on standard clinical scales; however, this was matched by an equal number of patients improving,” researchers observed. “The reasons for the physical improvement in an unexpectedly high proportion of patients must be addressed in future studies.”

Reference:
Højsgaard Chow H, Talbot J, Lundell H, et al. Dimethyl fumarate treatment of primary progressive multiple sclerosis: results of an open-label extension study. Mult Scler Relat Disord. Published online December 9, 2022. doi:10.1016/j.msard.2022.104458