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

Abstract

The coronavirus 2019 (COVID-19) pandemic is expected to linger. Decisions regarding initiation or continuation of diseasemodifying 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.

COVID-19 in ocrelizumab-treated people with multiple sclerosis

“…During the COVID-19 pandemic, many neurologists have adopted a cautious approach to treating MS by delaying or stopping DMTs, due to concerns that DMTs may increase the risk of a SARS-CoV-2 infection or the severity of COVID-19. To date, most published data on COVID-19 outcomes in people with MS are based on smaller case series including patients with various DMTs ( Zheng et al, 2020 ). In general, the emerging data seem to suggest that patients treated with DMTs are not at higher risk of contracting SARS-CoV-2 and seem to have similar risks and outcomes to the general population ( Zheng et al, 2020 ).…”

“…Depending on the mode of action of a DMT for MS, this may lead to different considerations for patient management. Current risk categorizations of DMTs are mostly based on theoretical considerations around the mode of action and the biology of COVID-19 ( Amor et al, 2020 ; Baker et al, 2020b ; Giovannoni et al, 2020 ; Zheng et al, 2020 ). In future, the potential impact of each DMT on SARS-CoV-2 vaccines will need to be considered and may depend on the type of vaccine used ( Zheng et al, 2020 ).…”

COVID-19 in teriflunomide-treated patients with multiple sclerosis: A case report and literature review

“…The use of disease-modifying therapies (DMTs) is considered the most important factor for determining such risk (Brownlee et al, 2020) and there is wide discussion about the opportunity of continuing or stopping DMTs in MS patients with a diagnosis of DMTs could possibly increase the COVID-19 risks in PwMS because of their effects on immune system. Available data suggest that the risk is higher for second-generation DMTs (Zheng et al, 2020;Sormani et al, 2020). On the other side, it has been hypothesized that DMTs could also have a protective effect against COVID-19 because they could modulate the immune response against SARS-CoV-2, one of the factors associated with the clinical severity of COVID-19, and in some cases, they could exert a direct antiviral effect (Baker et al, 2020;Rostami Mansoor and Ghasemi-Kasman, 2020).…”

Behavioral practices of patients with multiple sclerosis during Covid-19 pandemic

“…Some conflicting evidence, however, revealed that most disease-modifying therapies for MS do not particularly target the innate immune system, which confers protection against SARS-CoV-2, and few have any major long-term impact on CD8 T cells to limit protection against Covid-19 [ 8 ]. Some other researchers have also shown that immunosuppressive therapy neither appears to have a significant consequence on infection with SARS-CoV-2 nor seems to marshal a severe disease course in many cases [ 9 , 10 ]. However, it is generally agreed that some drugs, such as interferons, glatiramer acetate, and teriflunomide seem to be safe.…”