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MS Treatment Extends Time to First Symptom in Trial in People with Radiologically Isolated Syndrome (RIS)

December 15, 2022

The first results from attempts to prevent or slow the development of multiple sclerosis have been published. In a clinical trial, dimethyl fumarate (Tecfidera®, Biogen) extended the time before the development of a first neurological symptom significantly more than placebo. Participants had a rare condition called radiologically isolated syndrome, with MS-like brain lesions on MRI but no detectable symptoms. This first completed trial of its kind adds to the idea that early treatment is protective against disease activity. Additional trials, now underway, should help determine who among those with RIS may benefit from early treatment.
  • Background: Although not considered a course of MS, radiologically isolated syndrome (RIS) is a rare condition involving people who show lesions on MRI of the brain and/or spinal cord that are consistent with those found in MS and who have no detectable neurological symptoms or abnormalities. Previous research suggests that about half of those classified as having RIS are likely to develop definite MS within ten years.
  • The Study: Dr. Darin Okuda (University of Texas Southwestern Medical Center) led a team from 12 MS centers who recruited 87 people with RIS and randomly assigned them either to oral dimethyl fumarate (240 mg twice daily) or to inactive placebo for 96 weeks. The primary goal of the study was to determine whether treatment would extend the time it took for participants to develop a first neurological symptom. The team also assessed disease activity on MRI scans.
  • Fourteen people in each group did not complete the study, in part because the study was terminated early due to low trial enrollment.
  • Results: Significantly fewer participants who received dimethyl fumarate experienced a neurological symptom compared to those on placebo. Treatment also significantly reduced the occurrence of MRI-detected disease activity.
  • Moderate adverse effects were more common in people taking dimethyl fumarate, and included mostly infections and muscle pain/weakness.
  • Impact: This first completed trial of its kind adds to the idea that early treatment is protective and supports the idea that MS can begin well before symptoms emerge. Further study is needed, in larger numbers of people with RIS. Additional trials are underway, including:
  • A trial of teriflunomide (Aubagio®, Genzyme Sanofi) that is ongoing outside of the U.S. and no longer recruiting
  • A trial of ocrelizumab (Ocrevus®, Genentech) that is recruiting 100 people at sites in the U.S. – site information is available on the study’s page
  • A trial testing a tuberculosis vaccine that is recruiting in Italy
“Dimethyl Fumarate Delays Multiple  Sclerosis in Radiologically Isolated Syndrome” by Drs.  Darin T. Okuda, Orhun Kantarci, Christine Lebrun-Frénay, Maria Pia Sormani, Christina J. Azevedo, Francesca Bovis, Le H. Hua, Lilyana Amezcua, Ellen M. Mowry, Christophe Hotermans, Jason Mendoza, John S. Walsh, Christian von Hehn, Wendy S. Vargas, Stacy Donlon, Robert T. Naismith, Annette Okai, Gabriel Pardo, Pavle Repovic, Olaf Stüve, Aksel Siva, and Daniel Pelletier, is published in Annals of Neurology (published online November 18, 2022).

About Multiple Sclerosis

Multiple sclerosis is an unpredictable disease of the central nervous system. Currently there is no cure. Symptoms vary from person to person and may include disabling fatigue, mobility challenges, cognitive changes, and vision issues. An estimated 1 million people live with MS in the United States. Early diagnosis and treatment are critical to minimize disability. Significant progress is being made to achieve a world free of MS.

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