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使用CD20抑制剂治疗免疫介导疾病患者的COVID-19结局:一项比较队列研究。

COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study.

作者信息

Patel Naomi J, D'Silva Kristin M, Hsu Tiffany Y-T, DiIorio Michael, Fu Xiaoqing, Cook Claire, Prisco Lauren, Martin Lily, Vanni Kathleen M M, Zaccardelli Alessandra, Zhang Yuqing, Sparks Jeffrey A, Wallace Zachary S

机构信息

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA.

Clinical Epidemiology Program, Mongan Institute, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

medRxiv. 2021 Aug 9:2021.08.05.21261643. doi: 10.1101/2021.08.05.21261643.

Abstract

OBJECTIVE

Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown.

METHODS

We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression.

RESULTS

We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis.

CONCLUSIONS

Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic.

KEY MESSAGES

Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown. CD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar. There is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic.

摘要

目的

接受CD20抑制剂治疗的免疫介导疾病患者可能因体液免疫受损而出现更差的新冠病毒病(COVID-19)结局,但与普通人群的差异尚不清楚。

方法

我们确定了在2020年1月31日至2021年1月31日期间,在PCR确诊COVID-19的索引日期前一年内接受CD20抑制剂治疗的免疫介导疾病患者。将COVID-19患者的对照者按年龄、性别和PCR日期以5:1的比例进行匹配。使用Cox回归估计CD20抑制剂使用者与对照者住院、机械通气和死亡的风险比(HR)及95%置信区间(CI)。

结果

我们确定了114例因免疫介导疾病接受CD20抑制剂治疗的COVID-19患者(平均年龄55岁,70%为女性)和559例匹配的COVID-19对照者(平均年龄54岁,女性占70%)。接受CD20抑制剂治疗的患者死亡率高于匹配的对照者(调整后HR 2.16;95%CI:1.03至4.54)。住院风险(调整后HR 0.88;95%CI:0.62至1.26)和机械通气风险(调整后HR 0.82;95%CI:0.36至1.87)相似。根据适应证类型(如风湿性或神经疾病)和CD20抑制剂使用时间(<1年或≥1年)进行分析,以及排除间质性肺疾病、癌症患者和COVID-19诊断前使用糖皮质激素的患者后,也观察到了类似趋势。

结论

在COVID-19之前因免疫介导疾病接受CD20抑制剂治疗的患者,COVID-19后的死亡率高于匹配的对照者,这凸显了在当前大流行期间降低CD20抑制剂使用者额外风险的迫切需求。

关键信息

接受CD20抑制剂治疗的免疫介导疾病患者的COVID-19结局可能比接受其他免疫调节药物治疗的患者更差,但与普通人群的差异尚不清楚。接受CD20抑制剂治疗的患者死亡率比匹配的普通人群对照者高出两倍多,尽管住院和机械通气风险相似。在当前COVID-19大流行期间,迫切需要为接受CD20抑制剂治疗的免疫介导疾病患者制定降低风险的策略,如使用严重急性呼吸综合征冠状病毒2单克隆抗体或加强疫苗接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12a0/8366799/8397ee378191/nihpp-2021.08.05.21261643v1-f0001.jpg

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