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. 2021 Mar;35(3):317-330.
doi: 10.1007/s40263-021-00804-1. Epub 2021 Mar 20.

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

Anthony T Reder  1 , Diego Centonze  2   3 , Maria L Naylor  4 , Anjali Nagpal  4 , Rajani Rajbhandari  4 , Arman Altincatal  4 , Michelle Kim  4 , Aaron Berdofe  4 , Maha Radhakrishnan  4 , Eunice Jung  4 , Alfred W Sandrock  4 , Karen Smirnakis  4 , Catrinel Popescu  5 , Carl de Moor  4
Affiliations

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

Anthony T Reder et al. CNS Drugs. 2021 Mar.

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.

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Conflict of interest statement

Anthony T. Reder has received unrestricted research support from Bayer, Biogen, Roche-Genentech, Mallinckrodt, Merck-Serono, and Novartis, and is a consultant for Bayer, Biogen, NKMax America, Merck-Serono, Novartis, and Roche-Genentech. Diego Centonze is an advisory board member of Almirall, Celgene, BMS, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva and has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. He is also the principal investigator in clinical trials for Abbvie, Zambon, Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, and Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen, Celgene, Lundbeck, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva. Maria L. Naylor, Anjali Nagpal, Rajani Rajbhandari, Arman Altincatal, Michelle Kim, Aaron Berdofe, Maha Radhakrishnan, Eunice Jung, Alfred W. Sandrock, Karen Smirnakis, Catrinel Popescu, and Carl de Moor are employees and hold stock/stock options in Biogen.

Figures

Fig. 1
Fig. 1
Study design. COVID-19 coronavirus disease 2019, DMT disease-modifying therapy, MS multiple sclerosis, PCR polymerase chain reaction
Fig. 2
Fig. 2
Odds of developing coronavirus disease 2019 among patients with multiple sclerosis by disease-modifying therapy class. Multivariate logistic regression analyses were adjusted for age, sex, race, and body mass index and for comorbidities such as hypertension, diabetes, cardiovascular disease, cancer, chronic obstructive pulmonary disease, and chronic kidney disease. The adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) based on profile penalized likelihood estimates are presented. Sample size for disease-modifying therapy use: dihydro-orotate dehydrogenase (DHO-DH) inhibitor, n = 1446; interferon (IFN)-β, n = 6509; glatiramer acetate, n = 6840; sphingosine-1-phosphate receptor (S1PR) modulator, n = 2699; anti-CD20, n = 3568; fumarate, n = 4439; anti-VLA-4, n = 2080. Disease-modifying therapies prescribed for multiple sclerosis were categorized by mechanism of action, as described in Sect. 2.2.1
Fig. 3
Fig. 3
Cumulative incidence of coronavirus disease 2019 (COVID-19), and hospitalizations, and deaths due to COVID-19 in patients with multiple sclerosis (MS) or systemic lupus erythematosus (SLE). The cumulative incidence was calculated for patients with MS or SLE with an open prescription for a disease-modifying therapy based on the IBM Explorys database as of 30 November 2020. Percentage and sample size are shown
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