Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide

Bollo, Luca; Guerra, Tommaso; Bavaro, Davide Fiore; Monno, Laura; Saracino, Annalisa; Angarano, Gioacchino; Paolicelli, Damiano; Trojano, María; Iaffaldano, Pietro

doi:10.1016/j.jns.2020.117011

Cited by 36 publications

(46 citation statements)

References 9 publications

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“…Stopping fingolimod has been linked to severe rebound MS activity, thus timely initiation of another potent DMT is recommended to avoid the need for hospitalization and the increased exposure risk [ 59 ]. In addition to the two cases mentioned above, six additional cases of COVID-19 infection in patients with MS taking fingolimod have been reported to the time of this writing [ 38 , 41 , 60 – 62 ]. Four additional self-reported cases on Twitter have been reported as well [ 42 ].…”

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 98%

“…Based on influenza vaccine studies, teriflunomide is unlikely to reduce the protective immune response against the future SARS-CoV-2 viral protein or inactivated vaccine [43]. In addition, successful development of anti-SARS-CoV-2 antibodies at levels comparable to patients not receiving immunotherapies has been described in a patient taking teriflunomide after COVID-19 infection [41]. Live-attenuated vaccines are not recommended with teriflunomide.…”

Section: Potential Relevance To the Covid-19 Pandemic And Possible Rimentioning

confidence: 99%

“…One fatal case of COVID-19 infection in a patient taking teriflunomide has been reported but the patient had advanced secondary progressive MS and comorbid myotonic dystrophy [ 38 ]. Seven other cases of COVID-19 infection in patients taking teriflunomide have been reported to the time of this writing, all with self-limiting courses despite continued teriflunomide therapy during the infection in most of them [ 39 – 41 ]. One additional self-reported case with full recovery at home has been described in a paper surveying self-reported cases on social media [ 42 ].…”

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 99%

“…Fingolimod has been shown to dampen both the cellular and humoral protective immune responses against vaccines [ 63 ]. In addition, one of the reported patients with COVID-19 infection taking fingolimod was noted to have attenuated production of anti-SARS-CoV-2 antibodies after exposure [ 41 ]. Fingolimod is also incompatible with live-attenuated vaccines and its impact on viral vector vaccines is unknown.…”

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 98%

Section: Potential Relevance To the Covid-19 Pandemic And Possible Rimentioning

confidence: 99%

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 99%

Section: Current Multiple Sclerosis Disease-modifying Therapiesmentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2020

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“…In the most severe case, high levels of IL-6 were reported and intubation was necessary. If discontinuation of fingolimod increased the risk of acute respiratory distress syndrome, or if fingolimod effect per se is attributable to this course, remains unknown [81][82][83][84][85]. Notably, two patients remained completely asymptomatic during COVID-19 infection [86].…”

Section: Glatiramer Acetatementioning

confidence: 99%

Immunology of COVID‐19 and disease‐modifying therapies: The good, the bad and the unknown

Zrzavy

Wimmer

Rommer

et al. 2020

Euro J of Neurology

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The outbreak of the SARS‐CoV‐2 pandemic, caused by a previously unknown infectious agent, posed unprecedented challenges to healthcare systems and unmasked their vulnerability and limitations worldwide. Patients with long‐term immunomodulatory/suppressive therapies, as well as their physicians, were and are concerned about balancing the risk of infection and effects of disease‐modifying therapy. Over the last few months, knowledge regarding SARS‐CoV‐2 has been growing tremendously, and the first experiences of infections in patients with multiple sclerosis (MS) have been reported. This review summarizes the currently still limited knowledge about SARS‐CoV‐2 immunology and the commonly agreed modes of action of approved drugs in immune‐mediated diseases of the central nervous system (MS and neuromyelitis optica spectrum disorder). Specifically, we discuss whether immunosuppressive/immunomodulatory drugs may increase the risk of SARS‐CoV‐2 infection and, conversely, may decrease the severity of a COVID‐19 disease course. At present, it can be recommended in general that none of those therapies with a definite indication needs to be stopped per se . A possibly increased risk of infection for most medications is accompanied by the possibility to reduce the severity of COVID‐19. Despite the knowledge gain over the last few months, current evidence remains limited, and, thus, further clinical vigilance and systematic documentation is essential.

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Sphingosine-1 Phosphate Receptor Modulators

Herrera

Bodro

2022

Infectious Complications in Biologic and Targeted Therapies

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Seroconversion and indolent course of COVID-19 in patients with multiple sclerosis treated with fingolimod and teriflunomide

Cited by 36 publications

References 9 publications

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

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

Immunology of COVID‐19 and disease‐modifying therapies: The good, the bad and the unknown

Sphingosine-1 Phosphate Receptor Modulators

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