Multiple sclerosis 2021 – a look ahead


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To start off the new year, NeuroSens asked some MS experts from across Canada what developments in multiple sclerosis research and management we can expect to see. Some issues were necessarily related to COVID-21. But the prognosticators also identified several important questions that may be answered in the months ahead.

Here are the Top 5 Picks for the most important developments in MS to anticipate in the year ahead.

Clinical practice

1. COVID vaccination: At present, two mRNA vaccines are slowly being distributed across Canada. The upside: 325,000 vaccine doses have been administered as of January 11. The downside: at this rate it will take about 4 years to vaccinate everyone.

There are two key issues with respect to the MS population. The Canadian National Advisory Committee on Immunization (NACI) currently recommends that the COVID-19 vaccine should not be routinely offered to individuals who are immunosuppressed or have an autoimmune condition (Recommendations 4 and 5) due to a lack of evidence regarding vaccine effectiveness in these populations ( These are recommendations rather than contraindications: NACI also states that vaccine may be offered if the benefits outweigh the potential risks. There will be similar safety and effectiveness considerations with the next-generation COVID vaccines when they become available. There are also concerns about the safety of viral vector vaccines in an MS population. The wild card is whether the current crop of vaccines will be effective against new CoV-2 strains.

Secondly, NACI has cautioned that there is insufficient evidence on the safety and effectiveness COVID-19 vaccines when administered to patients receiving a monoclonal antibody for the treatment of non-COVID disease. Preliminary reports have suggested an increased risk of ICU admission with ocrelizumab in MS patients (Simpson-Yap et al. ECTRIMS 2020; SS02.04). The year should bring further clarity to this issue.

A key clinical question is whether disease-modifying therapy (DMT) regimens can be modified without loss of efficacy. Will less frequent dosing of cell-depleting therapies (ocrelizumab, cladribine, alemtuzumab) still be effective? Watch for real-world database analyses to address this question in the months ahead.

2. Can you see me now? Video consults have become our Zoom-and-gloom companions in the pandemic, but will they ever leave? One prediction: a hybrid model of patient care may emerge that combines in-person and virtual visits. It is generally acknowledged that a neurological work-up must be hands-on and cannot be properly done at a distance (Yeroushalmi et al. J Telemed Telecare 2020;26:400-413). However, when an examination is not required, there is the potential to alleviate some of the burden to patients of in-office visits, especially for those living remotely. For video to become part of clinical practice, provincial payers will need to adequately reimburse for telehealth services, and the federal government will need to do more to ensure equitable access to broadband services. Video will likely become an integral part of neurology congresses, which will have a negative impact on attendance. On-line attendance has been substantially less than in-person events, so some meetings may not be financially viable in the years ahead.  


3. New treatments: The impending launch of ofatumumab, an anti-CD20 monoclonal antibody administered subcutaneously every four weeks, is expected to have the greatest impact on MS therapeutics this year. The phase III ASCLEPIOS I and II trials were published last summer and reported a >50% reduction in annualized relapse rate and a 32% relative reduction in 6-month disability worsening with ofatumumab versus teriflunomide (Hauser et al. N Engl J Med 2020;383:546-557). Ofatumumab was also associated with a 26% relative reduction in serum neurofilament-light chain levels. A potential advantage of ofatumumab during the pandemic is self-administration at home rather than at an infusion centre. Expect to see additional data on ofatumumab at this year’s congresses.


4. Neurofilament-light chain (NfL): NfL has emerged as a lead biomarker of disease severity, progression and treatment response. Single molecule array (Simoa) technology to test blood or serum samples is becoming more widespread, so we may see sNfL become part of routine MS care this year. Post-hoc analyses of sNfL have been done in progressive MS studies such as the EXPAND trial of siponimod (Kuhle et al. AAN 2018; abstract S8.006); more recent studies, such as the ASCLEPIOS trial of ofatumumab, have used NfL as a study endpoint. The application of NfL findings requires some clarification, as discussed in a review published last year by the International Progressive MS Alliance (Kapoor et al. Neurology 2020;95:436-444). Expect to see additional work this year to determine reference NfL values, and further attempts to correlate NfL with clinical/radiological endpoints.

5. Radiologically isolated syndrome (RIS): It has been a matter of some debate whether individuals with no neurological event but with an incidental finding of MRI lesions suggestive of MS (RIS) should be treated with a DMT (Alshamrani et al. Expert Rev Neurother 2017;17:441-447). Last year saw the first long-term follow-up of RIS, which reported a 10-year cumulative risk of a clinical event of 51% (Lebrun-Frenay et al. Ann Neurol 2020;88:407-417). Two RIS treatment trials are expected to produce results this year: the TERIS study of teriflunomide, and the ARISE study of dimethyl fumarate. A third trial of BCG vaccine as an RIS treatment is ongoing.

The Year in Review – virtual EBM and SPMS – Survey

Which of the following will have the greatest impact on your clinical practice in 2021?

Which change to the treatment landscape will have the greatest impact on your prescribing this year?

What research question is most important to address this year?

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