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.

中文翻译：

---

多发性硬化症患者的 COVID-19：与疾病改善疗法的关联

背景

多发性硬化症 (MS) 的疾病改善疗法 (DMT) 以免疫为目标，并有可能增加严重急性呼吸系统综合症冠状病毒-2 (SARS-CoV-2) 感染的风险并改变其临床病程。我们评估了 MS (PwMS) 患者的这些风险。

客观的

本研究的目的是描述 PwMS 中 2019 年冠状病毒病 (COVID-19) 感染的总体风险、严重病程和 COVID-19 感染的潜在人群水平预测因素，并使用一组患者提供背景系统性红斑狼疮（SLE）。此外，还评估了不同 MS DMT 与 COVID-19 发病率和临床病程的关联。来自 Biogen 全球安全数据库的安全数据还提供了在接受 Biogen MS 疗法治疗的患者中报告的 COVID-19 病例。

方法

IBM ^® Explorys 电子健康记录数据库包含来自美国医疗保健网络的超过 72,000,000 名患者，确定了 MS 或 SLE 患者，无论是否有聚合酶链反应确认的 COVID-19。使用逻辑回归（根据年龄、性别、体重指数、合并症和种族/民族进行调整）比较了 DMT 类别中 COVID-19 的累积发病率、住院率和死亡人数。作为评估安全性数据的辅助数据源，Biogen MS 疗法的 COVID-19 报告是从 Biogen 的全球安全数据库中提取和描述的。

结果

在 Explorys 中发现了 30,478 个具有开放 DMT 处方的 PwMS；344 人 COVID-19 呈阳性。获得 COVID-19 的最重要风险因素是合并症评分 ≥ 1、体重指数 ≥ 30 和黑人/非洲血统。SLE 患者也发现了类似的危险因素。与所有其他 MS DMT 相比，MS 患者在接受干扰素 (0.61%) 和醋酸格拉替雷 (0.51%) 治疗后患 COVID-19 的可能性较小（均p < 0.001）；抗 CD20 治疗与最高风险相关（3.45%；p < 0.0001）。在 Biogen 全球安全数据库中，我们确定了 1217 名 COVID-19 阳性患者，他们接受了肌内干扰素 β-1a、聚乙二醇干扰素 β-1a、那他珠单抗、富马酸二甲酯、富马酸地罗西美或氨吡啶的治疗。

结论

合并症、肥胖和黑人/非洲血统，但与年龄无关，与 PwMS 中较高的 SARS-CoV-2 感染风险相关。在接受治疗的 MS 队列中，干扰素和醋酸格拉替雷与 COVID-19 风险降低相关，而抗 CD20 疗法与风险增加相关。接受 Biogen MS 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复制性和效力。