Neurology
Multiple Sclerosis
Reducing Relapse Rates and Disease Progression With Disease-Modifying Therapies in Patients With Multiple Sclerosis
Overview
The disease-modifying therapies (DMTs) represent the best strategy currently available to slow the natural course of progressive forms of multiple sclerosis (MS). Early intervention with such therapies may help prevent permanent damage in the central nervous system, reduce relapse rates, and reduce the progression of disability. There are over a dozen DMTs approved by the FDA for use in relapsing forms of MS. Guidelines from the American Academy of Neurology (AAN) include criteria for initiating DMTs and also identify key clinical and patient-level factors involved in selecting from the available therapies. With respect to the development of future disease-modifying agents for MS, our featured expert notes the importance of strong biomarkers that are linked to neurodegenerative mechanisms.
Expert Commentary
Dean Wingerchuk, MD, FRCP(C), MSc
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“We hope that by reducing relapse rates and measurable disease progression in a 2- to 3-year period, which is typical for most phase 3 clinical trials, patients who are compliant with their medication will experience sustained and meaningful clinical benefit over many years.”
The purpose of DMTs is to reduce relapse rates and measurable disease progression in patients with relapsing-remitting MS, and now in patients with primary progressive MS. DMTs that are currently US Food and Drug Administration (FDA) approved for the treatment of patients with relapsing-remitting MS are interferon beta-1a, interferon beta-1b, pegylated interferon beta-1a, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, and ocrelizumab. All of the drugs received FDA approval based on the results of clinical trials where they were shown to reduce the annualized relapse rates by 29% to 69%, compared with placebo or an active comparator.
The AAN recommends that clinicians offer DMTs to patients with relapsing-remitting MS who have recently experienced clinical relapses or magnetic resonance imaging activity. In clinical trials, most of the DMTs significantly reduced disability progression (as measured by Expanded Disability Status Scale), compared with placebo or an active comparator, in patients with relapsing-remitting MS. Ocrelizumab is the only DMT that has been shown to alter disease progression in patients with primary progressive MS who are ambulatory, and is recommended by the AAN for the treatment of patients in this population who are likely to benefit from the therapy. In addition, results of a recently completed phase 3 clinical trial showed that siponimod reduced the risk of disability progression in patients with secondary progressive MS.
We hope that by reducing relapse rates and measurable disease progression in a 2- to 3-year period, which is typical for most phase 3 clinical trials, patients who are compliant with their medication will experience sustained and meaningful clinical benefit over many years. If we had confidence in biomarkers that were linked to neurodegenerative mechanisms, and also linked to clinical progression, we could target treatments better for clinical trials and probably shorten length of trials and be more confident in their results.
References
Kappos L, Bar-Or A, Cree BAC, et al; EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018;391(10127):1263-1273.
Pardo G, Jones DE. The sequence of disease-modifying therapies in relapsing multiple sclerosis: safety and immunologic considerations [published correction appears in J Neurol. 2017;264(12):2375-2377]. J Neurol. 2017;264(12):2351-2374.
Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: disease-modifying therapies for adults with multiple sclerosis: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(17):777-788.
Torkildsen Ø, Myhr KM, Bø L. Disease-modifying treatments for multiple sclerosis – a review of approved medications. Eur J Neurol. 2016;23 Suppl 1:18-27.
