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

Anthony T Reder, Diego Centonze, Maria L Naylor, Anjali Nagpal, Rajani Rajbhandari, Arman Altincatal, Michelle Kim, Aaron Berdofe, Maha Radhakrishnan, Eunice Jung, Alfred W Sandrock, Karen Smirnakis, Catrinel Popescu, Carl de Moor

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)317-330
Number of pages14
JournalCNS Drugs
Issue number3
Publication statusPublished - Mar 2021


  • Adolescent
  • Adult
  • African Americans/statistics & numerical data
  • Aged
  • Aged, 80 and over
  • Alemtuzumab/therapeutic use
  • Azathioprine/therapeutic use
  • COVID-19/epidemiology
  • Cladribine/therapeutic use
  • Comorbidity
  • Crotonates/therapeutic use
  • Cyclophosphamide/therapeutic use
  • Cyclosporine/therapeutic use
  • Databases, Factual
  • Dimethyl Fumarate/therapeutic use
  • European Continental Ancestry Group/statistics & numerical data
  • Female
  • Fingolimod Hydrochloride/therapeutic use
  • Hospitalization/statistics & numerical data
  • Humans
  • Immunologic Factors/therapeutic use
  • Immunosuppressive Agents/therapeutic use
  • Incidence
  • Interferon-beta/therapeutic use
  • Logistic Models
  • Lupus Erythematosus, Systemic/drug therapy
  • Male
  • Methotrexate/therapeutic use
  • Middle Aged
  • Mitoxantrone/therapeutic use
  • Multiple Sclerosis/drug therapy
  • Mycophenolic Acid/therapeutic use
  • Natalizumab/therapeutic use
  • Obesity/epidemiology
  • Risk Factors
  • Rituximab/therapeutic use
  • SARS-CoV-2
  • Toluidines/therapeutic use
  • United States/epidemiology
  • Young Adult


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