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Dimethyl fumarate (Tecfidera) reduced the risk of the first symptom manifestation of multiple sclerosis (MS) in people with radiologically isolated syndrome (RIS), data from the trial showed.

The risk of a first clinical demyelinating event over 96 weeks was reduced both in unadjusted (HR 0.18, 95% CI 0.05-0.63, P=0.007) and adjusted (HR 0.07, 95% CI 0.01-0.45, P=0.005) models with dimethyl fumarate treatment, reported Darin Okuda, MD, of the University of Texas Southwestern Medical Center in Dallas.

"This is the first clinical trial that really demonstrated the benefit of a given disease-modifying therapy in preventing a first acute clinical event in people with RIS," Okuda said in a late-breaking presentation at the 2022 meeting of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

The findings support the benefit of early intervention in the MS disease spectrum, Okuda observed. "In the future, we'd like to see further studies be performed to assess the impact on disability outcome measures following treatment for a meaningful amount of time," he added.

RIS represents the of MS. "Such individuals possess incidental anomalies, highly suggestive of multiple sclerosis, yet they lack typical symptoms and structural findings differ greatly from those seen in nonspecific white matter disease," Okuda noted.

The trial recruited people with RIS from March 2016 to October 2019 at 12 U.S. sites, randomizing 87 participants to dimethyl fumarate (44 people) or placebo (43 people).

"We leveraged two independent committees for this study," Okuda stated. "Both committees evaluated clinical data and imaging data through adjudicated consensus, and if screening was successful, patients were randomized one-to-one to receive dimethyl fumarate in accordance with the or placebo."

Formal clinical assessments were acquired at weeks 0, 48, 96, and at the time of a first clinical event. MRI scans were performed at weeks 0 and 96. "Ten of 87 individuals did not complete the full 96 weeks as the study was prematurely terminated by the study sponsor; the reason for that was because of the slow pace of recruitment," Okuda pointed out.

At baseline, mean ages were 43.6 in the treatment group and 44.8 in the placebo group. Both groups had 70% females and baseline Expanded Disability Status Scale () scores of 1 on a scale of 0 to 10. Nearly 90% of participants were white.

In the dimethyl fumarate group, six of 38 people had gadolinium-enhancing lesions at baseline; in the placebo group, two of 28 people did.

Adjusting for the number of gadolinium-enhancing lesions at baseline, there were fewer new or newly-enlarging T2-weighted hyperintense lesions in the dimethyl fumarate group compared with placebo (HR 0.20, 95% CI 0.04-0.94, P=0.042). Gadolinium enhancement was present in only one participant at week 96.

More moderate adverse reactions emerged in the dimethyl fumarate group (32%) than placebo (21%) but severe events were similar (5% vs. 9%, respectively). "We did not see anything remarkable with respect to adverse reactions," Okuda noted.

In a discussion after the presentation, Mark Freedman, MD, MSc, of the University of Ottawa in Canada, asked what percentage of participants had cervical cord lesions and whether those patients were more like to convert.

"Unfortunately, due to restrictions in funding, we weren't able to acquire spinal cord imaging in a well-organized, uniform manner," Okuda said.

"We haven't looked at our data in that way because not everyone actually had spinal cord imaging," he added. "We understand that this is one potential limitation for our study, in that there may have been an imbalance between groups in terms of who had spinal cord lesions."

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