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羟氯喹和托珠单抗治疗 COVID-19 患者:一项观察性研究。

Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study.

机构信息

Division of Outcomes and Value Research, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States of America.

Berry Consultants LLC, Austin, Texas, United States of America.

出版信息

PLoS One. 2020 Aug 13;15(8):e0237693. doi: 10.1371/journal.pone.0237693. eCollection 2020.

Abstract

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

摘要

羟氯喹被吹捧为 COVID-19 的一种潜在治疗方法。白细胞介素-6(IL-6)抑制剂托珠单抗也被提议作为重症患者的治疗方法。在这项从电子健康记录中提取的回顾性观察性队列研究中,我们旨在描述羟氯喹或托珠单抗治疗与住院 COVID-19 患者死亡率之间的关联。患者于 2020 年 3 月 1 日至 2020 年 4 月 22 日在美国新泽西州的一个由 13 家医院组成的网络中住院,聚合酶链反应(PCR)结果对 SARS-CoV-2 呈阳性。随访至 2020 年 5 月 5 日。在 2512 名患有 COVID-19 的住院患者中,有 547 人(22%)死亡,1539 人(61%)出院,426 人(17%)仍住院。1914 人(76%)至少接受了一剂羟氯喹,1473 人(59%)接受了羟氯喹联合阿奇霉素。通过倾向评分模型调整不平衡后,与未接受任何药物治疗相比,住院期间接受任何羟氯喹治疗的患者死亡率没有显著差异(HR,0.99 [95%CI,0.80-1.22]),单独使用羟氯喹(HR,1.02 [95%CI,0.83-1.27])或羟氯喹联合阿奇霉素(HR,0.98 [95%CI,0.75-1.28])。单独使用羟氯喹、单独使用阿奇霉素、联合使用或不使用任何药物的患者的 30 天未调整死亡率分别为 25%、20%、18%和 20%。在 547 名可评估 ICU 患者中,包括 134 名在 ICU 接受托珠单抗治疗的患者,一项探索性分析发现,托珠单抗治疗与生存获益呈趋势相关(调整后的 HR,0.76 [95%CI,0.57-1.00]),30 天未调整死亡率分别为 46%和 56%。这项观察性队列研究表明,羟氯喹,单独使用或联合使用阿奇霉素,与住院 COVID-19 患者的生存获益无关。托珠单抗在 ICU 患者中显示出死亡率降低的趋势关联。我们的发现仅限于住院患者,在等待随机试验结果时必须谨慎解释。试验注册:Clinicaltrials.gov 标识符:NCT04347993。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a316/7425928/2298fad8448e/pone.0237693.g001.jpg

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