Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis

Steve Simpson-Yap, Edward De Brouwer, Tomas Kalincik, Nick Rijke, Jan A. Hillert, Clare Walton, Gilles Edan, Yves Moreau, Tim Spelman, Lotte Geys, Tina Parciak, Clement Gautrais, Nikola Lazovski, Ashkan Pirmani, Amin Ardeshirdavanai, Lars Forsberg, Anna Glaser, Robert McBurney, Hollie Schmidt, Arnfin B. BergmannStefan Braune, Alexander Stahmann, Rodden Middleton, Amber Salter, Robert J. Fox, Anneke Van Der Walt, Helmut Butzkueven, Raed Alroughani, Serkan Ozakbas, Juan I. Rojas, Ingrid Van Der Mei, Nupur Nag, Rumen Ivanov, Guilherme Sciascia Do Olival, Alice Estavo Dias, Melinda Magyari, Doralina Brum, Maria Fernanda Mendes, Ricardo N. Alonso, Richard S. Nicholas, Johana Bauer, Aníbal Sebastián Chertcoff, Anna Zabalza, Georgina Arrambide, Alexander Fidao, Giancarlo Comi, Liesbet Peeters

Research output: Contribution to journalArticlepeer-review

157 Scopus citations


Background and ObjectivesPeople with multiple sclerosis MS are a vulnerable group for severe coronavirus disease 2019 COVID-19, particularly those taking immunosuppressive disease-modifying therapies DMTs. We examined the characteristics of COVID-19 severity in an international sample of people with MS.MethodsData from 12 data sources in 28 countries were aggregated sources could include patients from 1-12 countries. Demographic age, sex, clinical MS phenotype, disability, and DMT untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit ICU admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale EDSS score.ResultsSix hundred fifty-seven 28.1% with suspected and 1,683 61.9% with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01-2.41; aOR 2.43, 95% CI 1.48-4.02 and ICU admission aOR 2.30, 95% CI 0.98-5.39; aOR 3.93, 95% CI 1.56-9.89, although only rituximab was associated with higher risk of artificial ventilation aOR 4.00, 95% CI 1.54-10.39. Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization aOR 1.75, 95% CI 1.29-2.38; aOR 2.76, 95% CI 1.87-4.07 and ICU admission aOR 2.55, 95% CI 1.49-4.36; aOR 4.32, 95% CI 2.27-8.23, but only rituximab was associated with artificial ventilation aOR 6.15, 95% CI 3.09-12.27. Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization aOR 1.86, 95% CI 1.13-3.07; aOR 2.88, 95% CI 1.68-4.92 and ICU admission aOR 2.13, 95% CI 0.85-5.35; aOR 3.23, 95% CI 1.17-8.91, but only rituximab was associated with ventilation aOR 5.52, 95% CI 1.71-17.84. Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity.DiscussionUsing the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.

Original languageEnglish (US)
Pages (from-to)E1870-E1885
Issue number19
StatePublished - Nov 9 2021
Externally publishedYes

ASJC Scopus subject areas

  • Clinical Neurology


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