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Associations of Disease-Modifying Therapies With COVID-19 Severity in Multiple Sclerosis.
Simpson-Yap, Steve; De Brouwer, Edward; Kalincik, Tomas; Rijke, Nick; Hillert, Jan A; Walton, Clare; Edan, Gilles; Moreau, Yves; Spelman, Tim; Geys, Lotte; Parciak, Tina; Gautrais, Clement; Lazovski, Nikola; Pirmani, Ashkan; Ardeshirdavanai, Amin; Forsberg, Lars; Glaser, Anna; McBurney, Robert; Schmidt, Hollie; Bergmann, Arnfin B; Braune, Stefan; Stahmann, Alexander; Middleton, Rodden; Salter, Amber; Fox, Robert J; van der Walt, Anneke; Butzkueven, Helmut; Alroughani, Raed; Ozakbas, Serkan; Rojas, Juan I; van der Mei, Ingrid; Nag, Nupur; Ivanov, Rumen; Sciascia do Olival, Guilherme; Dias, Alice Estavo; Magyari, Melinda; Brum, Doralina; Mendes, Maria Fernanda; Alonso, Ricardo N; Nicholas, Richard S; Bauer, Johana; Chertcoff, Aníbal Sebastián; Zabalza, Anna; Arrambide, Georgina; Fidao, Alexander; Comi, Giancarlo; Peeters, Liesbet.
  • Simpson-Yap S; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • De Brouwer E; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Kalincik T; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Rijke N; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Hillert JA; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Walton C; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Edan G; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Moreau Y; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Spelman T; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Geys L; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Parciak T; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Gautrais C; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Lazovski N; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Pirmani A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Ardeshirdavanai A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Forsberg L; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Glaser A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • McBurney R; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Schmidt H; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Bergmann AB; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Braune S; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Stahmann A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Middleton R; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Salter A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Fox RJ; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • van der Walt A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Butzkueven H; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Alroughani R; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Ozakbas S; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Rojas JI; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • van der Mei I; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Nag N; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Ivanov R; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Sciascia do Olival G; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Dias AE; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Magyari M; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Brum D; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Mendes MF; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Alonso RN; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Nicholas RS; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Bauer J; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Chertcoff AS; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Zabalza A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Arrambide G; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Fidao A; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Comi G; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
  • Peeters L; From the CORe (S.S.-Y., T.K.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N., A.F.), Melbourne School of Population & Global Health, University of Melbourne, Parkville, Australia; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Hobart, Australia; ESA
Neurology ; 97(19): e1870-e1885, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1523377
ABSTRACT
BACKGROUND AND

OBJECTIVES:

People 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.

METHODS:

Data 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.

RESULTS:

Six 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.

DISCUSSION:

Using 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Hospitalization / Multiple Sclerosis Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Neurology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 / Hospitalization / Multiple Sclerosis Type of study: Cohort study / Observational study / Prognostic study / Randomized controlled trials Topics: Long Covid Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Neurology Year: 2021 Document Type: Article