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April 19, 2021

Discontinuation of Disease-Modifying Therapy in Multiple Sclerosis: Should We Stay or Should We Go?

Author Affiliations
  • 1MS Center Amsterdam, Amsterdam UMC, Location VUmc, Amsterdam, the Netherlands
  • 2Department of Neurology, Rennes University Hospital, Rennes, France
  • 3Rocky Mountain Multiple Sclerosis Center at Anschutz Medical Campus, University of Colorado, Denver
JAMA Neurol. Published online April 19, 2021. doi:10.1001/jamaneurol.2021.0764

Treatment options for multiple sclerosis (MS) have increased dramatically since the introduction of the first disease-modifying therapy (DMT), interferon beta-1b, in the early 1990s. While treatment variability remains high, in many industrialized countries, treatment begins after a first episode of MS and often continues indefinitely. Thus, we are now increasingly confronted with aging patients treated for decades with DMT. However, the natural disease course of MS is highly variable and changes with age and disease duration.1 In younger patients, pathology within the central nervous system is dominated by an adaptive immune response. Over time, especially at older ages and with progressive MS, this pathological profile changes to a more compartmentalized inflammation. Clinically, disease activity in younger patients is predominantly that of acute relapses and focal inflammatory changes on magnetic resonance imaging (MRI) scans (ie, new T2 lesions or gadolinium-enhancing lesions) that are caused by this adaptive immune response, whereas many older patients have either developed slowly progressive disability with minimal interruption by acute relapses (and radiological disease activity) or stabilized with neither relapses nor progression.2

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    1 Comment for this article
    Multiple Sclerosis (MS): Passage of Time May Change the Environmental Influences, Too
    Gary Ordog, MD, DABEM, DABMT | County of Los Angeles, Department of Health Services, (retired)
    Thank you for your article on the treatment of Multiple Sclerosis. Your discussion of discontinuing the Disease Modifying Therapy after several years and at a certain age is very apt. I would also like to point out that over the years the environmental factors may also change, those that are contributing to the illness. Most significantly, if the patient has had to move to a new habitat during their treatment(1-3). Again, thank you.

    1. Ordog GJ: Multiple Sclerosis Cluster: Myotoxic Leukoencephalopathy. January 2005: Journal of Investigative Medicine 53(1):S161.5-S161 DOI: 10.2310/6650.2005.00005.475

    2. Ordog GJ, Ordog TV: MS Western Conference
    Journal, JIM AFMR BMJ 2020 June; Multiple Sclerosis: Caused by Mycotoxic Leukoencephalopathy. DOI - 10.1136/jim-2020-MW.83 Abstracts 1082 J Investig Med 2020;68:1026–1124.

    3. Ordog GJ, Ordog TV: Multiple Sclerosis: Mycotoxic Leukoencephalopathy 15 Year Follow-up. May 2020. Journal of Investigative Medicine. British Medical Journal. May 2020. Journal of Investigative Medicine 2020(68):906-650. DOI: 10.1136/jim-2020-ERM.38