Multiple Sclerosis Disease-Modifying Therapy and the COVID-19 Pandemic: Implications on the Risk of Infection and Future Vaccination

Crystal Zheng, Indrani Kar, Claire Kaori Chen, Crystal Sau, Sophia Woodson, Alessandro Serra, Hesham Abboud, Crystal Zheng, Indrani Kar, Claire Kaori Chen, Crystal Sau, Sophia Woodson, Alessandro Serra, Hesham Abboud

Abstract

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of disease-modifying therapy for multiple sclerosis have to consider the potential relevance to the pandemic. Understanding the mechanism of action and the possible idiosyncratic effects of each therapeutic agent on the immune system is imperative during this special time. The infectious side-effect profile as well as the route and frequency of administration of each therapeutic agent should be carefully considered when selecting a new treatment or deciding on risk mitigation strategies for existing therapy. More importantly, the impact of each agent on the future severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) vaccine should be carefully considered in treatment decisions. Moreover, some multiple sclerosis therapies may have beneficial antiviral effects against SARS-CoV-2 while others may have beneficial immune-modulating effects against the cytokine storm and hyperinflammatory phase of the disease. Conventional injectables have a favorable immune profile without an increased exposure risk and therefore may be suitable for mild multiple sclerosis during the pandemic. However, moderate and highly active multiple sclerosis will continue to require treatment with oral or intravenous high-potency agents but a number of risk mitigation strategies may have to be implemented. Immune-modulating therapies such as the fumerates, sphinogosine-1P modulators, and natalizumab may be anecdotally preferred over cell-depleting immunosuppressants during the pandemic from the immune profile standpoint. Within the cell-depleting agents, selective (ocrelizumab) or preferential (cladribine) depletion of B cells may be relatively safer than non-selective depletion of lymphocytes and innate immune cells (alemtuzumab). Patients who develop severe iatrogenic or idiosyncratic lymphopenia should be advised to maintain social distancing even in areas where lockdown has been removed or ameliorated. Patients with iatrogenic hypogammaglobulinemia may require prophylactic intravenous immunoglobulin therapy in certain situations. When the future SARS-CoV-2 vaccine becomes available, patients with multiple sclerosis should be advised that certain therapies may interfere with mounting a protective immune response to the vaccine and that serological confirmation of a response may be required after vaccination. They should also be aware that most multiple sclerosis therapies are incompatible with live vaccines if a live SARS-CoV-2 vaccine is developed. In this article, we review and compare disease-modifying therapies in terms of their effect on the immune system, published infection rates, potential impact on SARS-CoV-2 susceptibility, and vaccine-related implications. We propose risk mitigation strategies and practical approaches to disease-modifying therapy during the COVID-19 pandemic.

Conflict of interest statement

CZ, IK, CKC, and CS report no financial disclosures. SW is a consultant and a speaker for Biogen, Novartis, and Sanofi-Genzyme. AS is a consultant and speaker for Biogen and is supported in part by Career Development Award #IK2RX001180 from the US Department of Veterans Affairs, Rehabilitation Research and Development Service. HA received research grants from Novartis and Genentech to conduct clinical trials. He received consulting fees from Biogen, Genentech, Alexion, and Viela Bio. He also received speaker honoraria from Biogen, Genentech, Celgene, Sanofi-Genzyme, Alexion, and Viela Bio.

Figures

Fig. 1
Fig. 1
Proposed practical approach to disease-modifying therapy (DMT) selection and risk mitigation during the coronavirus disease 2019 (COVID-19) pandemic. −ve negative, +ve positive, ALC absolute lymphocyte count, CD19 cluster of differentiation 19, DMF dimethyl fumarate, DRF diroximel fumarate, GA glatiramer acetate, Ig immunoglobulin, IVIG intravenous immunoglobulins, JCV John Cunningham virus, MS multiple sclerosis

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