The Effect of Disease-Modifying Therapies on the Immune System in Patients with Multiple Sclerosis: Impact on COVID-19 Infection and Vaccination

March 2021

In this review article, the authors note that some disease-modifying therapies (DMTs) may increase the risk of COVID-19 infection in patients with multiple sclerosis (MS), some DMTs may have a negative impact on the efficacy of some COVID-19 vaccines (and many are incompatible with live vaccines), and that the route and frequency of administration and infectious side-effect profile of each therapy should be considered when devising risk mitigation strategies for patients.

“Understanding the impact of each DMT on the immune system, its associated infection risks, and its potential impact on future vaccination is imperative for the safe management of MS during the COVID-19 pandemic,” they wrote.

The authors evaluate each agent in terms of the impact of its mechanism of action (MOA) on a patient’s immune system, infectious side effects, and its potential relevance to the COVID-19 pandemic and possible risk mitigation strategies. In brief, the following are several examples of the information and insights presented for select MS therapies:

  • Interferon-beta: The MOA of this therapy means it is not likely to affect the early or delayed immune response to COVID-19 or significantly increase a patient’s susceptibility to infection. It does not reduce the protective immune response to vaccines and will likely be compatible with a viral protein or inactivated form of COVID-19 vaccine.
  • Teriflunomide: Based on its MOA and infectious side-effect profile, teriflunomide may slightly increase a patient’s susceptibility to COVID-19. It is likely safe to continue treatment in patients who are infected with COVID-19 who are asymptomatic or mildly symptomatic.
  • Dimethyl fumarate: Their immune profile suggests these oral agents may increase susceptibility to COVID-19 infection in patients with moderate to severe lymphopenia but is likely safe in patients with mild or no lymphopenia. Ongoing treatment is an option in these patients unless absolute lymphocyte count falls below 800/mm3. The need for periodic laboratory monitoring increases COVID-19 exposure risk, but oral administration is safer compared with intravenous agents.
  • Natalizumab: As a non–cell-depleting agent, it is unlikely treatment with natalizumab increases COVID-19 susceptibility and is unlikely to have a negative impact on viral protein and inactivated forms of COVID-19 vaccines. It is likely safe to continue treatment during the pandemic, even in infected patients. The authors wrote that natalizumab “is perhaps the safest potent DMT for patients with highly active MS during the pandemic.” However, they also noted that the intravenous route of administration of this medication “is not ideal during the pandemic as it increases the exposure risk at infusion centers. The monthly infusion frequency is the highest among all intravenous DMTs further increasing exposure risk.”

Similar information is also provided for glatiramer acetate, sphingosine-1-phosphate modulators, ocrelizumab, alemtuzumab, and cladribine.

In their concluding remarks, the authors wrote: “The ideal DMT during the pandemic is one with a moderate-to-high potency against MS without increasing the risk of [COVID-19] exposure and susceptibility, and without a negative impact on the future vaccine. A potential benefit against the virus or its associated cytokine storm phase in infected patients is an additional factor to consider when deciding on DMT initiation.” However, because none of the currently approved DMTs fulfill all these criteria, the authors recommended that “a thorough discussion of the benefits and risks of each agent should take place prior to DMT initiation.”


Zheng C, Kar I, Chen CK, et al. Multiple sclerosis disease-modifying therapy and the COVID-19 pandemic: implications on the risk of infection and future vaccination. CNS Drugs. 2020;34:879-896.

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