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多发性硬化症患者的 COVID-19:与疾病修正治疗的关联

COVID-19 in Patients with Multiple Sclerosis: Associations with Disease-Modifying Therapies.

作者信息

Reder Anthony T, Centonze Diego, Naylor Maria L, Nagpal Anjali, Rajbhandari Rajani, Altincatal Arman, Kim Michelle, Berdofe Aaron, Radhakrishnan Maha, Jung Eunice, Sandrock Alfred W, Smirnakis Karen, Popescu Catrinel, de Moor Carl

机构信息

Department of Neurology and Brain Research Institute, University of Chicago, Chicago, IL, USA.

Laboratory of Synaptic Immunopathology, Department of Systems Medicine, Tor Vergata University, Rome, Italy.

出版信息

CNS Drugs. 2021 Mar;35(3):317-330. doi: 10.1007/s40263-021-00804-1. Epub 2021 Mar 20.

Abstract

BACKGROUND

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS).

OBJECTIVE

The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies.

METHODS

The IBM Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database.

RESULTS

30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine.

CONCLUSIONS

Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.

摘要

背景

用于治疗多发性硬化症(MS)的疾病修正疗法(DMTs)作用于免疫系统,有可能增加严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的风险并改变其临床病程。我们评估了MS患者(PwMS)的这些风险。

目的

本研究的目的是描述2019冠状病毒病(COVID-19)感染的总体风险、严重疾病病程以及PwMS中COVID-19感染的潜在人群水平预测因素,并通过一组系统性红斑狼疮(SLE)患者提供背景信息。此外,还评估了不同的MS DMTs与COVID-19发病率和临床病程之间的关联。还展示了来自渤健全球安全数据库的关于接受渤健MS疗法治疗的患者中COVID-19报告的安全数据。

方法

来自美国医疗网络的超过7200万患者的IBM Explorys电子健康记录数据库识别出患有MS或SLE的患者,无论是否经聚合酶链反应确诊为COVID-19。使用逻辑回归比较DMT类别中的COVID-19累积发病率、住院率和死亡率(根据年龄、性别、体重指数、合并症和种族/族裔进行调整)。作为评估安全数据的二级数据源,从渤健全球安全数据库中提取并描述了关于渤健MS疗法的COVID-19报告。

结果

在Explorys中识别出30478例开具了DMT处方的PwMS;344例为COVID-19阳性。感染COVID-19的最显著风险因素是合并症评分≥1、体重指数≥30以及黑人/非洲血统。SLE患者也发现了类似的风险因素。与所有其他MS DMTs相比,MS患者接受干扰素(0.61%)和醋酸格拉替雷(0.51%)治疗时发生COVID-19的可能性较小(均p<0.001);抗CD20疗法的风险最高(3.45%;p<0.0001)。在渤健全球安全数据库中,我们识别出1217例接受肌肉注射干扰素β-1a、聚乙二醇干扰素β-1a、那他珠单抗、富马酸二甲酯、二甲基富马酸酯或氨吡啶治疗的COVID-19阳性患者。

结论

合并症、肥胖和黑人/非洲血统而非年龄与PwMS中SARS-CoV-2感染风险较高相关。在接受治疗的MS队列中,干扰素和醋酸格拉替雷与降低COVID-19风险相关,而抗CD20疗法与增加风险相关。接受渤健MS疗法治疗的患者的COVID-19安全报告与Explorys数据库和MS文献一致,说明了这种方法的可重复性和有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5e3/8005391/2005b98d805d/40263_2021_804_Fig1_HTML.jpg

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