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Background and Objectives Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. Methods Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. Results Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1–7] and 7% [95%CI 4–11]), ICU/artificial ventilation (2% [95% CI 0–4] and 4% [95% CI 2–6]), and death (1% [95% CI 0–2] and 2% [95% CI 1–4]) (predicted marginal effects). Untreated patients had 5% (95%CI2–8),3%(95%CI1–5),and1%(95%CI0–3)higherprobabilitiesofthe3respectivelevels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. Discussion Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: the operational costs linked to this study are funded by the Multiple Sclerosis International Federation (MSIF) and the Multiple Sclerosis Data Alliance (MSDA), acting under the umbrella of the European Charcot Foundation (ECF). The MSDA receives income from a range of corporate sponsors, recently including Biogen, Bristol-Myers Squibb (formerly Celgene), Canopy Growth Corporation, Genzyme, Icometrix, Merck, Mylan, Novartis, QMENTA, Quanterix, and Roche. MSIF receives income from a range of corporate sponsors, recently including Biogen, Bristol-Myers Squibb (formerly Celgene), Genzyme, Med-Day, Merck, Mylan, Novartis, and Roche. This work was supported by the Flemish Government under the Onderzoeksprogramma Artifici¨ele Intelligentie (AI) Vlaanderen programme and the Research Foundation Fladers (FWO) for ELIXIR Belgium— Flanders (FWO) for ELIXIR Belgium. The central platform was provided by QMENTA, and the computational resources used in this work were provided by Amazon. The statistical analysis was carried out at CORe, The University of Melbourne, with support from NHMRC (1129189 and 1140766). Acknowledgment The authors thank the patients comprising the studies and registries that are part of this project, and the authors hope that the results of this work may be of benefit to them and patients like them.

Made available in DSpace on 2022-04-28T19:46:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-09 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. CORe Department of Medicine and Neuroepidemiology Unit Melbourne School of Population and Global Health Menzies Institute for Medical Research University of Tasmania ESAT-STADIUS KU Leuven Department of Neurology Melbourne MS Centre Royal Melbourne Hospital MS International Federation Department of Clinical Neuroscience Swedish MS Registry Department of Neurology CHU Pontchaillou Karolinska Institutet Biomedical Research Institute-Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Department of Computer Science and AI KU Leuven QMENTA Medpace Reference Laboratories Molecular Unit IConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData German MS-Register by the National MS Society MS Forschungs- und Projektentwicklungs-gGmbH MS Register Swansea University COViMS Division of Biostatistics Washington University in St. Louis Mellen Center for Multiple Sclerosis Cleveland Clinic Department of Neuroscience Central Clinical School Monash University Al-Amiri Hospital Kuwait City Dokuz Eylul University Neurology Department Hospital Universitario de CEMIC RELACOEM Australian MS Longitudinal Study Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset ABEM-Brazilian MS Patients Association Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista Unesp Faculdade de Medicina REDONE.br-Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders Irmandade da Santa Casa de Misericórdia de São Paulo Multiple Sclerosis University Center Ramos Mejia Hospital-EMA Imperial College Swansea University Mental Health Area MS and Demyelinating Diseases Hospital Británico de Buenos Aires EMA Servei de Neurologia-Neuroimmunologia Centre d'Esclerosi Múltiple de Catalunya Cemcat Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat Autònoma de Barcelona Institute of Experimental Neurology Ospedale San Raffaele Universidade Estadual Paulista Unesp Faculdade de Medicina

Background: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). Methods: We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Results: Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. Conclusions: The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration. We thank the sponsors of the MSDA and all the data custodians who completed and shared the questionnaire with the MSDA community. Special thanks to all the people involved in the data collection and management of the different data sources and registries. Funding/Support We thank our sponsors. The MSDA receives income from a range of corporate sponsors, recently including Biogen, Bristol Myers Squibb, Janssen Pharmaceuticals, Merck, Mylan, Novartis, QMENTA, and Roche

Made available in DSpace on 2020-12-12T02:15:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Multiple Sclerosis International Federation Background: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Objectives: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Methods: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. Results: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. Conclusions: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS. Biomedical Research Institute and Data Science Institute Hasselt University Department of Medical Informatics University Medical Center Göttingen MS International Federation ESAT-STADIUS KU Leuven Biomedical Research Institute and Data Science Institute Hasselt University Diepenbeek Belgium/ESAT-STADIUS KU Leuven Clinical Outcomes Research (CORe) Unit The University of Melbourne Department of Neurology CHU Pontchaillou Neuroepidemiology Unit Melbourne School of Population Global Health The University of Melbourne Department of Computer Science and Leuven.AI KU Leuven QMENTA Department of Clinical Neuroscience Swedish MS Registry iConquerMS People-Powered Research Network Accelerated Cure Project for MS NeuroTransData Study Group NeuroTransData MS Forschungs- und Projektentwicklungs-gGmbH UK MS Register COViMS St Louis USA/ Division of Biostatistics Washington University in St. Louis COViMS USA/National Multiple Sclerosis Society Neurology Department Hospital Universitario de CEMIC MSBase Registry Department of Neuroscience Central Clinical School Monash University The Australian MS Longitudinal Study (AMSLS) Menzies Institute for Medical Research University of Tasmania Bulgarian SmartMS COVID-19 Dataset LEOSS Department of Neurology Katholisches Klinikum Bochum Brazilian Multiple Sclerosis Association (ABEM) Cleveland Clinic MS COVID-19 Registry Mellen MS Center Cleveland Clinic Icometrix – Icompanion OptimiseMS Preventive Neurology Unit Queen Mary University of London The Danish Multiple Sclerosis Registry Department of Neurology University Hospital Rigshospitalet Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders RELACOEM Mental Health Area EMA MS and Demyelinating Diseases Hospital Británico de Buenos Aires – EMA Department of Neurology Strasbourg University Hospital COVISEP Institute of Experimental Neurology Ospedale San Raffaele Melbourne MS Centre Department of Neurology Royal Melbourne Hospital Institut du Cerveau ICM APHP – Hôpital Pitié Salpêtrière Sorbonne University Menzies Institute for Medical Research University of Tasmania Imperial College London Swansea University Multiple Sclerosis University Center Ramos Mejia Hospital – EMA Universidade Estadual Paulista (Unesp) Faculdade de Medicina Botucatu/REDONE – Brazilian Registry of Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders