New MS Guideline Addresses Starting, Switching, and Stopping Disease-modifying Therapy

Alexander D. Rae-Grant, MD

The American Academy of Neurology has issued 30 recommendations for disease-modifying therapy (DMT) for multiple sclerosis. The recommendations include guidance on starting, switching, and stopping DMTs. Notably, they recommend starting DMTs early on before the disease has progressed.

The National Institute of Health estimates that multiple sclerosis (MS) affects 400,000 Americans. These patients experience a wide range of symptoms including muscle weakness, numbness, chronic pain, fatigue, vision problems, bladder dysfunction, and cognitive and emotional problems. However, the recommendations specifically address DMTs, which slow disease progress but do not specifically treat MS symptoms.

The American Academy of Neurology’s (AAN) new guideline is an update to their 2002 clinical practice guideline. The options for MS treatment have changed markedly since then, with over 17 treatments currently available in the US and others nearing commercial approval.

“The treatment landscape for people with MS has changed dramatically over the last decade,” said lead author Alexander D. Rae-Grant, MD, of Cleveland Clinic in Cleveland, Ohio, and a Fellow of the American Academy of Neurology. “We now have a number of disease-modifying therapies to choose from that may help treat MS by changing how the disease affects people over time by slowing the disease process.”

A multidisciplinary panel developed the guideline, basing their recommendations on a systematic review of available studies. Each recommendation was supported by a rationale drawing from sources including the review, other evidence not in the review, principles of care, and inference from evidence.

The panel additionally assigned each recommendation a level of obligation to indicate the confidence in that recommendation. These levels were indicated by the modifiers must (Level A), should (Level B), and may (Level C). Just 2 starting recommendations were assigned Level A.

“Clinicians must engage in an ongoing dialogue regarding treatment decisions throughout the disease course with people with MS,” they said in the starting recommendation 2, adding that clinicians must incorporate the patient’s preferences regarding safety, route of administration, lifestyle, cost, efficacy, common adverse effects, and tolerability when considering a DMT.

While DMTs are designed to slow and stabilize the disease progress, some patients experience a return of MS activity while taking a DMT. The second Level A starting recommendation states that clinicians must advise patients with MS who are taking DMTs to notify clinicians of any new or worsening symptoms. In these cases, the person with MS may need to switch to a new therapy.

The panel also considered that patients whose MS is stable may wish to stop DMT treatment. According to the guideline few studies have evaluated the benefits or risks of stopping treatment. However, they issued 3 recommendations for clinicians and patients considering this option.

The AAN panelists suggested topics for future research, including higher potency treatment initially vs standard stepped-care protocols, longer term studies, studies focused on patient-centered outcomes, comparative effectiveness studies, better definitions of highly active MS, and studies of various switching strategies.

The guideline was published in the April 23, 2018, online issue of Neurology® and presented at the 70th AAN Annual Meeting in Los Angeles, April 2018. The guideline is endorsed by the Multiple Sclerosis Association of America and the National Multiple Sclerosis Society.