Secondary Logo

Share this article on:

In the Clinic-Multiple Sclerosis: What You Should Know about the Updated AAN MS Guideline

Samson, Kurt

doi: 10.1097/01.NT.0000533816.85006.cc
Features
Back to Top | Article Outline

ARTICLE IN BRIEF

Figure

Figure

The lead author of a new AAN guideline on disease modifying therapies for adults with multiple sclerosis highlights the important new findings of the review.

The AAN has issued a new practice guideline on disease-modifying therapies for treating multiple sclerosis (MS), including starting, switching, or halting treatment.

Although the recommendations do not formally replace the 2002 guidelines issued by the AAN, they do offer updates and include comprehensive analysis of the current medical literature on the safety and effectiveness of different disease-modifying therapies (DMTs), as well as clinical recommendations on their use and other issues. The full text of the guideline was published in the April 24 edition of Neurology.

The guideline addresses DMTs for primary and secondary progressive multiple sclerosis (PPMS/SPMS), clinically isolated demyelinating syndrome (CIS), and relapsing-remitting MS (RRMS).

In a telephone interview, Neurology Today asked AAN guideline development panel member Alexander Rae-Grant, MD, FAAN, professor of neurology and director for education at the Cleveland Clinic's Mellen Center for MS, to discuss some of the highlights of the new recommendations.

Back to Top | Article Outline

WHY WAS AN UPDATE NEEDED?

The treatment landscape has changed dramatically since 2002, and it is difficult for neurologists, even MS specialists, to keep up with all the permutations. Many new DMTs have been approved, with differing mechanisms of action, risk profiles, and monitoring requirements. This new guideline provides 30 recommendations, with specific guidance on starting, switching, and stopping DMTs, and includes recommendations on patient monitoring for response to treatment as well as adverse events and drug- and individual-specific risk factors.

It also includes strategies for increasing patient engagement as well as individualizing treatment, monitoring adherence, comorbidity assessments, and DMT risks, including counseling about progressive multifocal leukoencephalopathy (PML) risk with the use of natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate.

Back to Top | Article Outline

WHAT FINDINGS WOULD YOU SAY ARE MOST IMPORTANT?

I think the most important finding came from MS patients on the panel. What we learned from them is the importance of an ongoing dialogue on treatment issues, including when to start or stop treatment, safety concerns, and the importance of personalized therapy.

Figure

Figure

Figure

Figure

It is also important that many studies have now confirmed that a single demyelinating episode event can put patients at increased risk of a future MS diagnosis, with the highest risk within five years.

Back to Top | Article Outline

STARTING WITH RRMS, WHICH DMTs HAVE THE BEST EFFICACY PROFILE?

All of the drugs showed some efficacy against relapse and lesions of the brain and spinal cord detected on magnetic resonance imaging (MRI) lesions. Alemtuzumab and ocrelizumab are more effective than IFN-beta-1a 44 μg (interferon-beta), and dimethyl fumarate, fingolimod, various interferons, mitoxantrone, natalizumab, pegylated interferon, and teriflunomide were more effective than placebo.

Fingolimod, IFN-beta-1a 44 μg subcutaneous three times weekly, and natalizumab had the high-quality evidence of reducing new or enlarging lesions. There was also high-quality evidence supporting ocrelizumab over IFN-beta-1a in reducing the annualized relapse rate, the risk of new or enlarging lesions, and loss of parenchymal volume. Also, alemtuzumab was found more effective than IFN-β-1a 44 μg subcutaneously three times per week in reducing the annualized relapse rate in patients who experienced a relapse on interferon-beta or glatiramer acetate.

Back to Top | Article Outline

WHAT ABOUT OPTIONS FOR TREATING PPMS AND SPMS?

Ocrelizumab is the only DMT with moderate evidence of being able to alter disease progression in ambulatory patients with PPMS, and it should be offered to patients unless contraindicated. Certain drugs may be helpful for SPMS patients who have relapses or active new lesions on MRI, provided they are ambulatory with or without assistance.

For example, IFN-beta reduces the risk of relapse but does not delay disability progression. Clinicians should assess the likelihood of future relapse on an individual basis based on patient age, disease duration, relapse history, MRI-detected relapse frequency, severity, and time since the most recent relapse or new lesions seen on MRI. Clinicians may advise discontinuing treatment for SPMS patients who have not been ambulatory for two years or more in the absence of ongoing relapses or MRI lesions.

Back to Top | Article Outline

HOW DOES THE GUIDELINE ADDRESS THE RISK OF PML WITH NEWER TREATMENTS?

PML is a serious safety concern, especially in patients on natalizumab with elevated JVC antibody levels, and clinicians should counsel people with MS considering natalizumab, fingolimod, rituximab, ocrelizumab, and dimethyl fumarate about risk. Longer duration of use and prior immunosuppression may increase PML risk even further in patients taking natalizumab. Clinicians should consider switching DMTs for patients on natalizumab who are or become JCV antibody–positive, especially with higher index levels.

Back to Top | Article Outline

WHAT STEPS ARE RECOMMENDED BEFORE INITIATING TREATMENT?

Clinicians should counsel patients about treatment options and evaluate their readiness or reluctance to initiate DMT. They should emphasize the importance of therapy for qualified candidates while also addressing safety concerns. Discussion should also focus on the route of administration, lifestyle factors, cost, efficacy, common adverse effects (AEs), and tolerability, comorbid disease, adverse health behaviors, and potential interactions with their current medications. Clinicians should also discuss barriers to adherence and counsel patients on depression and other factors that can affect outcomes.

Back to Top | Article Outline

WHAT SHOULD CLINICIANS KNOW ABOUT SWITCHING DMTs?

None of the available DMTs are completely effective against relapse and MRI lesion activity, but when a patient shows breakthrough disease activity switching to a medication with a different mechanism or efficacy profile may be beneficial. Evidence supports the higher efficacy of alemtuzumab, natalizumab, fingolimod, and ocrelizumab compared with previous injectable DMTs.

Clinicians should recognize that relapses or new lesions may develop before a DMT becomes effective. For patients who have been using a DMT long enough for the treatment to take full effect, clinicians should discuss switching if a patient has one or more relapses, two or more unequivocally new MRI-detected lesions, or increased disability over a treatment year.

Back to Top | Article Outline

WERE THERE ANY NOTABLE INSTRUCTIONS ABOUT STOPPING TREATMENTS?

No randomized controlled trials have directly addressed the question of whether, when, or why to discontinue DMTs in a RRMS patient with stable brain imaging and no evidence of relapse or disability progression. SPMS patients who have not been ambulatory for at least two years and have no signs of ongoing relapses or lesions may be eligible for discontinued treatment.

Also, although patients with clinically isolated syndrome who are on DMTs but have no disease activity may question the value of continuing treatment indefinitely, there are little data available about the potential risks of halting treatment. People with MS who are stable on DMTs also may question the continued value of DMTs, but if they stop these medications, continued monitoring may show subclinical disease activity or relapse activity indicating the potential need for resuming treatment.

We also provided a number of recommendations on whether or not to halt treatment during conception and pregnancy.

Back to Top | Article Outline

WHAT DOES THE GUIDELINE RECOMMEND FOR FUTURE RESEARCH?

Direct comparisons between the effectiveness of DMTs in different MS subpopulations is needed, as is study of whether or not high-potency treatment early in the disease course improves long-term outcomes or works better than standard stepped-care protocols. The ongoing search for biomarkers to predict DMT efficacy in different subpopulations is also needed, together with optimal switching strategies, long-term effects of DMT use, and whether switching DMTs versus continuing a DMT, despite continued disease activity, results in improved long-term outcomes.

More research into potential risks of treatment in pregnant women is also needed, especially about determining when DMTs should be stopped before conception, whether some agents are safer than others, and which agents might be safe enough to continue through conception and pregnancy in active disease. In addition, we need more research on the risk of return of disease activity during pregnancy or the postpartum period, on long-term disability risk, and quality of life when DMTs are discontinued during preconception, early pregnancy, or lactation

Back to Top | Article Outline

LINK UP FOR MORE INFORMATION:

•. 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 http://n.neurology.org/content/90/17/777. Neurology 2018;90:777–788.
    •. Rae-Grant A, Day GS, Marrie RA, et al Comprehensive systematic review summary: Disease-modifying therapies for adults with multiple sclerosis. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology http://n.neurology.org/content/90/17/789. Neurology 2018;90:789–800.
      •. Goodin DS, Frohman EM, Garmony J, et al Disease modifying therapies in multiple sclerosis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines http://n.neurology.org/content/58/2/169. Neurology 2002;58:169–178.
        © 2018 American Academy of Neurology