Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1212/WNL.0000000000012753 http://hdl.handle.net/11449/222740 |
Resumo: | 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. |
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Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple SclerosisBackground 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.CORe Department of Medicine and Neuroepidemiology UnitMelbourne School of Population and Global HealthMenzies Institute for Medical Research University of TasmaniaESAT-STADIUS KU LeuvenDepartment of Neurology Melbourne MS Centre Royal Melbourne HospitalMS International FederationDepartment of Clinical Neuroscience Swedish MS RegistryDepartment of Neurology CHU PontchaillouKarolinska InstitutetBiomedical Research Institute-Data Science Institute Hasselt UniversityDepartment of Medical Informatics University Medical CenterDepartment of Computer Science and AI KU LeuvenQMENTAMedpace Reference Laboratories Molecular UnitIConquerMS People-Powered Research Network Accelerated Cure Project for MSNeuroTransData Study Group NeuroTransDataGerman MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbHMS Register Swansea UniversityCOViMSDivision of Biostatistics Washington University in St. LouisMellen Center for Multiple Sclerosis Cleveland ClinicDepartment of Neuroscience Central Clinical School Monash UniversityAl-Amiri Hospital Kuwait CityDokuz Eylul UniversityNeurology Department Hospital Universitario de CEMICRELACOEMAustralian MS Longitudinal Study Menzies Institute for Medical Research University of TasmaniaBulgarian SmartMS COVID-19 DatasetABEM-Brazilian MS Patients AssociationDanish Multiple Sclerosis Registry Department of Neurology University Hospital RigshospitaletUniversidade Estadual Paulista Unesp Faculdade de MedicinaREDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum DisordersIrmandade da Santa Casa de Misericórdia de São PauloMultiple Sclerosis University Center Ramos Mejia Hospital-EMAImperial CollegeSwansea UniversityMental Health AreaMS and Demyelinating Diseases Hospital Británico de Buenos Aires EMAServei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya CemcatVall d'Hebron Institut de Recerca Vall d'Hebron Hospital UniversitariUniversitat Autònoma de BarcelonaInstitute of Experimental Neurology Ospedale San RaffaeleUniversidade Estadual Paulista Unesp Faculdade de Medicinaand Neuroepidemiology UnitMelbourne School of Population and Global HealthUniversity of TasmaniaKU LeuvenRoyal Melbourne HospitalMS International FederationSwedish MS RegistryCHU PontchaillouKarolinska InstitutetHasselt UniversityUniversity Medical CenterQMENTAMolecular UnitAccelerated Cure Project for MSNeuroTransDataMS Forschungs- und Projektentwicklungs-gGmbHSwansea UniversityCOViMSWashington University in St. LouisCleveland ClinicMonash UniversityKuwait CityDokuz Eylul UniversityHospital Universitario de CEMICRELACOEMBulgarian SmartMS COVID-19 DatasetABEM-Brazilian MS Patients AssociationUniversity Hospital RigshospitaletUniversidade Estadual Paulista (UNESP)REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum DisordersIrmandade da Santa Casa de Misericórdia de São PauloRamos Mejia Hospital-EMAImperial CollegeMental Health AreaEMACemcatVall d'Hebron Hospital UniversitariUniversitat Autònoma de BarcelonaOspedale San RaffaeleSimpson-Yap, SteveDe Brouwer, EdwardKalincik, TomasRijke, NickHillert, Jan A.Walton, ClareEdan, GillesMoreau, YvesSpelman, TimGeys, LotteParciak, TinaGautrais, ClementLazovski, NikolaPirmani, AshkanArdeshirdavanai, AminForsberg, LarsGlaser, AnnaMcBurney, RobertSchmidt, HollieBergmann, Arnfin B.Braune, StefanStahmann, AlexanderMiddleton, RoddenSalter, AmberFox, Robert J.Van Der Walt, AnnekeButzkueven, HelmutAlroughani, RaedOzakbas, SerkanRojas, Juan I.Van Der Mei, IngridNag, NupurIvanov, RumenSciascia Do Olival, GuilhermeDias, Alice EstavoMagyari, MelindaBrum, Doralina [UNESP]Mendes, Maria FernandaAlonso, Ricardo N.Nicholas, Richard S.Bauer, JohanaChertcoff, Aníbal SebastiánZabalza, AnnaArrambide, GeorginaFidao, AlexanderComi, GiancarloPeeters, Liesbet2022-04-28T19:46:29Z2022-04-28T19:46:29Z2021-11-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleE1870-E1885http://dx.doi.org/10.1212/WNL.0000000000012753Neurology, v. 97, n. 19, p. E1870-E1885, 2021.1526-632X0028-3878http://hdl.handle.net/11449/22274010.1212/WNL.00000000000127532-s2.0-85118110317Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeurologyinfo:eu-repo/semantics/openAccess2022-04-28T19:46:30Zoai:repositorio.unesp.br:11449/222740Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:34:05.257444Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
title |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
spellingShingle |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis Simpson-Yap, Steve |
title_short |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
title_full |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
title_fullStr |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
title_full_unstemmed |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
title_sort |
Associations of Disease-Modifying Therapies with COVID-19 Severity in Multiple Sclerosis |
author |
Simpson-Yap, Steve |
author_facet |
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 [UNESP] Mendes, Maria Fernanda Alonso, Ricardo N. Nicholas, Richard S. Bauer, Johana Chertcoff, Aníbal Sebastián Zabalza, Anna Arrambide, Georgina Fidao, Alexander Comi, Giancarlo Peeters, Liesbet |
author_role |
author |
author2 |
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 [UNESP] Mendes, Maria Fernanda Alonso, Ricardo N. Nicholas, Richard S. Bauer, Johana Chertcoff, Aníbal Sebastián Zabalza, Anna Arrambide, Georgina Fidao, Alexander Comi, Giancarlo Peeters, Liesbet |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
and Neuroepidemiology Unit Melbourne School of Population and Global Health University of Tasmania KU Leuven Royal Melbourne Hospital MS International Federation Swedish MS Registry CHU Pontchaillou Karolinska Institutet Hasselt University University Medical Center QMENTA Molecular Unit Accelerated Cure Project for MS NeuroTransData MS Forschungs- und Projektentwicklungs-gGmbH Swansea University COViMS Washington University in St. Louis Cleveland Clinic Monash University Kuwait City Dokuz Eylul University Hospital Universitario de CEMIC RELACOEM Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association University Hospital Rigshospitalet Universidade Estadual Paulista (UNESP) REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Ramos Mejia Hospital-EMA Imperial College Mental Health Area EMA Cemcat Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Ospedale San Raffaele |
dc.contributor.author.fl_str_mv |
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 [UNESP] Mendes, Maria Fernanda Alonso, Ricardo N. Nicholas, Richard S. Bauer, Johana Chertcoff, Aníbal Sebastián Zabalza, Anna Arrambide, Georgina Fidao, Alexander Comi, Giancarlo Peeters, Liesbet |
description |
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. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11-09 2022-04-28T19:46:29Z 2022-04-28T19:46:29Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1212/WNL.0000000000012753 Neurology, v. 97, n. 19, p. E1870-E1885, 2021. 1526-632X 0028-3878 http://hdl.handle.net/11449/222740 10.1212/WNL.0000000000012753 2-s2.0-85118110317 |
url |
http://dx.doi.org/10.1212/WNL.0000000000012753 http://hdl.handle.net/11449/222740 |
identifier_str_mv |
Neurology, v. 97, n. 19, p. E1870-E1885, 2021. 1526-632X 0028-3878 10.1212/WNL.0000000000012753 2-s2.0-85118110317 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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Neurology |
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info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
E1870-E1885 |
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Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
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1808129220357914624 |