COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies

Abstract

Background Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). Objective The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. Methods The IBM ® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. Results 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. Conclusions Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

Update on the management of multiple sclerosis during the COVID-19 pandemic and post pandemic: An international consensus statement

“…In the light of this, fingolimod is under investigation as a potential treatment for COVID-19-associated acute respiratory distress syndrome. Although some case studies suggest that fingolimod may increase the risk of severe COVID-19 ( Barzegar et al, 2020 ), this finding was not seen in larger cohorts ( Reder et al, 2021 ; Simpson-Yap et al, 2021 ; Sormani et al, 2020 ). Postponing treatment with fingolimod during COVID-19 times is not recommended.…”

“…It is therefore not surprising that teriflunomide could play a potential therapeutic role in COVID-19 through dual antiviral and immunomodulatory actions ( Maghzi et al, 2020 ). Teriflunomide has not been shown to increase the risk of severe COVID-19 ( Reder et al, 2021 ; Simpson-Yap et al, 2021 ; Sormani et al, 2020 ). There is no need to stop treatment or wait to start treatment with interferons, glatiramer acetate or teriflunomide in pwMS during COVID-19 times.…”

“…Glatiramer acetate also does not have systemic immunosuppressive properties and does not increase the risk of viral infections in pwMS ( Giovannoni, 2018 ). Interferons and glatiramer acetate have been associated with a lower risk of SARS-CoV-2 infection in PwMS ( Reder et al, 2021 ). Teriflunomide promotes cytostasis in T and B cells via selective inhibition of dihydro-orotate dehydrogenase, which is a key mitochondrial enzyme in de novo pyrimidine synthesis required by rapidly dividing lymphocytes ( Giovannoni, 2018 ).…”

“…However, there is only a slightly increased rate of infections in pwMS treated with DMF ( Giovannoni, 2018 ). DMF does not increase the risk of patients developing severe COVID-19 and stopping or delaying treatment with DMF during COVID-19 times is not recommended ( Reder et al, 2021 ; Simpson-Yap et al, 2021 ; Sormani et al, 2020 ). Fingolimod and sphingosine 1-phosphate receptor (S1PR) modulators cause reversible sequestration of lymphocytes in lymphoid tissues, which may increase the risk of infections ( Giovannoni, 2018 ).…”

“…severe increase in relapse relate) associated with stopping or delaying treatment with natalizumab by longer than 8 weeks ( Giovannoni, 2018 ). Natalizumab does not increase the risk of severe COVID-19 ( Reder et al, 2021 ; Simpson-Yap et al, 2021 ; Sormani et al, 2020 ) and stopping treatment with natalizumab or delaying its initiation during COVID-19 times is not recommended. Extended interval dosing of natalizumab (every 5–6 weeks) is recommended to allow patients to make fewer trips to the hospital and minimize their exposure risk as much as possible.…”