Multiple Sclerosis Treatment Guidelines

Overview

Professional societies of neurologists, including most prominently the American Academy of Neurology (AAN) and the European Academy of Neurology (EAN) periodically release recommendations to guide physicians in the selection of MS therapies. This section presents the 2018 AAN Guideline on Disease-Modifying Therapies for Adults with Multiple Sclerosis and the 2018 European Committee for Treatment and Research in Multiple Sclerosis/European Academy of Neurology (ECTRIMS/EAN) Guideline on the Pharmacological Treatment of People with Multiple Sclerosis, which are most recent guidelines on multiple sclerosis (MS) treatment from the respective societies. Note that these guidelines pre-date the approval of some newer therapies (including the S1P receptor modulators siponimod, ozanimod, ponesimod and the CD20-targeted mAbs ofatumumab and ublituximab) and may thus be outdated. The Section also presents a summary of the 2022 Best Practices in Multiple Sclerosis Therapies issued by the Consortium of Multiple Sclerosis Centers (CMSC), a professional organization focused specifically on MS care.

2018 AAN Guideline on Disease-Modifying Therapies for Adults with Multiple Sclerosis

The 2018 AAN guideline emphasizes the importance of patient engagement strategies and personalization of treatment plans, monitoring adherence to therapy and assessing disease comorbidities. They include 17 recommendations for initiating, 10 for changing and 3 for stopping disease-modifying therapies (DMTs) for MS in people with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) and progressive forms of MS (Table 4-1). This guideline follows the methods outlined in the 2011 version of the AAN guideline development process manual, which was updated in 2014. The updates included a new way to classify therapeutic studies, a formal method to prioritize guideline topics and a change in the order of steps for peer review. Each recommendation in the 2018 Guideline was assigned a Level of Obligation (A – must, B – should, C – may, U – no recommendation supported), which are shown in Table 4-1.

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2018 ECTRIMS/EAN Guideline on the Pharmacological Treatment of People with Multiple Sclerosis

In 2018, ECTRIMS and EAN jointly released a guideline on the treatment of MS, which comprised 21 recommendations (Table 4-2) organized into the following topics:

• Early treatment in CIS patients
• Treatment in patients with both relapsing and progressive established disease
• Monitoring of treatment response
• Treatment strategies in case of inadequate treatment response
• Treatment discontinuation and/or switch
• Treatment in special situations such as pregnancy.

To address these topics, clinical questions were formulated following the Patients-Intervention-Comparator-Outcome (PICO) format. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop the recommendations, aligning with the 2015 Practical Recommendations for the process of proposing, planning and writing neurological management guidelines by EAN task forces. The quality of evidence was assessed based on the risk of bias, while the strength of recommendation (strong or weak) was formulated based on the quality of evidence and the risk-benefit balance.

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2022 CMSC Best Practices in Multiple Sclerosis Therapies

The 2022 Best Practices document was released by the CMSC as an update to their earlier 2019 guidelines on DMT use. The document, based on a virtual roundtable of experts (convened during the COVID-19 pandemic), consists of “best practice” recommendations rather than prescriptive guidelines, organized into 10 thematic groups ranging from DMT selection for RRMS and progressive MS, DMT switching, the use of DMTs in specific populations, efficacy monitoring and others. Table 4-3 shows a summary of the best practices from the CMSC document; the interested reader is directed to consult the entire document (available at: https://www.mscare.org/page/practice_guidelines) for further details about the recommendations.

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Guideline Comparison

While the 2018 AAN and 2018 ECTRIMS/EAN guidelines are broadly similar, several notable differences exist. First, the AAN guideline explicitly considers adherence to DMT, while the ECTRIMS/EAN guideline does not. By contrast, the ECTRIMS/EAN guidelines stress the role of MS centers with appropriate infrastructure that can provide proper monitoring and assessment, while the AAN guidelines do not. The ECTRIMS/EAN guideline discusses MRI more extensively than does the AAN guideline. Unlike the ECTRIMS/EAN guideline, the AAN guideline contains a recommendation on the potential impact of teriflunomide and cyclophosphamide on male fertility. Finally, while both guidelines recommend against the use of DMTs in pregnant patients or those planning to conceive, the ECTRIMS/EAN guideline allows for the use of interferon or glatiramer acetate until pregnancy is confirmed in patients at high risk of relapse and even during pregnancy in some patients with highly active disease. Overall, several aspects of both these guidelines are now outdated due to the availability of new medications and new data regarding the safety of several DMTs in pregnancy and breast feeding.