COVID-19 在多发性硬化症全球数据共享倡议中的更新结果：抗 CD20 和其他与 COVID-19 严重程度相关的风险因素。
Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity.
机构信息
From the CORe (S.S.-Y., T.K., S.S.), Department of Medicine, and Neuroepidemiology Unit (S.S.-Y., N.N.), Melbourne School of Population & Global Health, The University of Melbourne; Menzies Institute for Medical Research (S.S.-Y.), University of Tasmania, Australia; ESAT-STADIUS (A.P., E.D.B., L.G., T.P., Y.M.), KU Leuven; Biomedical Research Institute-Data Science Institute (A.P., L.G., T.P.), Hasselt University, Belgium; MS Centre (T.K., L.M.P.), Department of Neurology, Royal Melbourne Hospital, Australia; Department of Medical Informatics (T.K.), University Medical Center Göttingen, Germany; MS International Federation (A.H., N.R.), London, United Kingdom; Department of Clinical Neuroscience (J.A.H., T.S.), Swedish MS Registry, Karolinska Institutet, Sweden; Department of Neurology (G.E.), CHU Pontchaillou, France; iConquerMS People-Powered Research Network (R.M., H.S.), Accelerated Cure Project for MS, Waltham, MA; NeuroTransData Study Group (A.B.B., S.B.), NeuroTransData, Neuburg an der Donau, Germany; German MS-Register by the National MS Society (A. Stahmann), MS Forschungs- und Projektentwicklungs-gGmbH; UK MS Register (R.M.M., R.S.N.), Swansea University; COViMS (A. Salter, B.B.); Division of Biostatistics (A. Salter), Washington University in St. Louis; Department of Neuroscience (A.V.d.W., H.B.), Central Clinical School, Monash University, Australia; Dokuz Eylul University (S.O.), İzmir; Department of Neurology (C.B.), Karadeniz Technical University, Trabzon; Department of Neurology (R.K.), University of Hacettepe, Turkey; Amiri Hospital (R.A.), Kuwait; Neurology Department (J.I.R.), Hospital Universitario de CEMIC; RELACOEM (J.I.R., R.N.A.), Buenos Aires, Argentina; The Australian MS Longitudinal Study (I.A.v.d.M.), Menzies Institute for Medical Research, University of Tasmania; ABEM-Brazilian MS Patients Association (G.S.d.O.); The Danish Multiple Sclerosis Registry (M.M.), Departement of Neurology, University Hospital Rigshospitalet, Denmark; Multiple Sclerosis University Center (R.N.A.), Ramos Mejia Hospital-EMA, Argentina; Imperial College London (R.S.N., A.M.), United Kingdom; MS and Demyelinating Diseases, Hospital Británico de Buenos Aires (A.S.C.), EMA, Argentina; Servei de Neurologia-Neuroimmunologia (A.Z.d.T., G.A.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Spain; icometrix (A.D., L.C.), Leuven, Belgium; Queen Mary University London (R.D.), United Kingdom; QMENTA (P.R., V.P.), Barcelona, Spain; and Casa di Cura del Policlinico and Università Vita Salute San Raffaele (G.C.), Italy.
出版信息
Neurol Neuroimmunol Neuroinflamm. 2022 Aug 29;9(6). doi: 10.1212/NXI.0000000000200021. Print 2022 Nov.
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% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels 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.
背景与目的
某些人口统计学和临床特征，包括使用某些疾病修正疗法（DMT），与多发性硬化症（MS）患者的严重急性呼吸综合征冠状病毒 2 感染严重程度有关。需要在大型国际样本中全面探索这些关系。
方法
从 27 个国家收集的临床医生报告的人口统计学/临床数据汇总到一个包含 5648 名疑似/确诊 2019 年冠状病毒病（COVID-19）患者的数据集中。使用多级混合效应有序概率和逻辑回归评估 COVID-19 严重程度结局（住院、入住重症监护病房[ICU]、需要人工通气和死亡），调整年龄、性别、残疾和 MS 表型。将 DMT 与聚乙二醇干扰素β-1a 进行单独比较，将抗 CD20 DMT 与其他 DMT 联合以及与那他珠单抗进行比较。
结果
在 5648 名患者中，922 名（16.6%）疑似 COVID-19，4646 名（83.4%）确诊 COVID-19。男性、年龄较大、进展性 MS 和更高的残疾与更严重的 COVID-19 相关。与聚乙二醇干扰素β-1a 相比，奥瑞珠单抗和利妥昔单抗与更高的住院（4%[95%CI 1-7]和 7%[95%CI 4-11]）、入住 ICU/人工通气（2%[95%CI 0-4]和 4%[95%CI 2-6]）和死亡（1%[95%CI 0-2]和 2%[95%CI 1-4]）（预测边际效应）的概率相关。未治疗的患者的 COVID-19 严重程度的 3 个水平的概率分别比聚乙二醇干扰素β-1a 高 5%（95%CI 2-8）、3%（95%CI 1-5）和 1%（95%CI 0-3）。与其他 DMT 联合用药和那他珠单抗相比，奥瑞珠单抗和利妥昔单抗与 COVID-19 严重程度的关联更为显著。所有关联在限制为确诊 COVID-19 时仍然存在/增强。
讨论
分析最大的多发性硬化症患者疑似/确诊 COVID-19 的国际真实世界数据集证实，使用抗 CD20 药物（奥瑞珠单抗和利妥昔单抗）以及男性、年龄较大、进展性 MS 和更高的残疾与 COVID-19 更严重的病程有关。
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