Drugs Used in the Treatment of Multiple Sclerosis During COVID-19 Pandemic: A Critical Viewpoint

Abstract

: Since COVID-19 has emerged as a word public health problem, attention has been focused on how immune suppressive drugs used for the treatment of autoimmune disorders influence the risk for SARS-CoV-2 infection and the development of the acute respiratory distress syndrome (ARDS). Here we discuss the disease-modifying agents approved for the treatment of multiple sclerosis (MS) within this context. Interferon (IFN)-1a and -1b, which display antiviral activity, could be protective in the early stage of COVID-19 infection, although SARS-CoV-2 may have developed resistance to IFNs. However, in the hyper inflammation stage, IFNs may become detrimental by facilitating macrophage invasion in the lung and other organs. Glatiramer acetate and its analogues should not interfere with the development of COVID-19 and may be considered safe. Teriflunomide, a first-line oral drug used in the treatment of relapsing-remitting MS (RRMS) may display antiviral activity by depleting cellular nucleotides necessary for viral replication. The other first-line drug, dimethyl fumarate, may afford protection against SARS-CoV-2 by activating the Nrf-2 pathway and reinforcing the cellular defences against oxidative stress. Concern has been raised on the use of second-line treatments for MS during COVID-19 pandemic. However, this concern is not always justified. For example, fingolimod, might be highly beneficial during the hyperinflammatory stage of COVID-19 for a number of mechanisms including the reinforcement of the endothelial barrier. Caution is suggested for the use of natalizumab, cladribine, alemtuzumab, and ocrelizumab, although MS disease recurrence after discontinuation of these drugs may overcome a potential risk for COVID-19 infection.

SARS-CoV-2 infection in multiple sclerosis patients: interaction with treatments, adjuvant therapies, and vaccines against COVID-19

“…Some authors consider that IFN-β treatment can be started and continued in the case of a SARS-CoV-2 infection [ 47 ]. However, other authors state that IFN-β could be protective in the early stages of infection, but could become harmful in the stages of hyperinflammation, by facilitating the invasion of the lungs and other organs by macrophages [ 48 , 49 ]. Despite this, both therapies are being tested as possible treatments in cases of SARS-CoV-2 infection [ 50 ].…”

Disease-modifying therapies and hematological disorders: a systematic review of case reports and case series

“…These therapies are generally safer than higher efficacy agents. On the other hand, monoclonal antibodies (ocrelizumab, natalizumab, alemtuzumab and ofatumumab), Sphingosine 1-phosphate receptor (S1PR) modulators (fingolimod, siponimod, ozanimod, and ponesimod), cladribine and mitoxantrone show higher efficacy profiles but they are also associated with greater risks of adverse drug reactions (ADRs) ( 9 , 10 ). DMTs have distinct pharmacodynamics properties, resulting in immunomodulatory and anti-inflammatory response, and consequently impact individual efficacy and tolerability profiles.…”

Safety of pathogenetic therapy for multiple sclerosis during the COVID-19 pandemic

“…ГА не ассоциируется с развитием COVID-19 и может считаться безопасным. Терифлуномид может проявлять противовирусную активность, истощая клеточные нуклеотиды, необходимые для репликации вируса, диметилфумаратобеспечить защиту от SARS-CoV-2, усиливая клеточную защиту от оксидативного стресса, финголимод потенциально может оказать благоприятное действие в гипервоспалительную стадию COVID-19, усиливая эндотелиальный барьер [88]. С определённой осторожностью рекомендуется применять натализумаб, алемтузумаб, кладрибин.…”