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托珠单抗治疗新型冠状病毒肺炎患者的倾向评分匹配队列研究

A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019.

作者信息

Lewis Tyler C, Adhikari Samrachana, Tatapudi Vasishta, Holub Meredith, Kunichoff Dennis, Troxel Andrea B, Montgomery Robert A, Sterman Daniel H

机构信息

Department of Pharmacy, NYU Langone Health, New York, NY.

Transplant Institute, NYU Langone Health, New York, NY.

出版信息

Crit Care Explor. 2020 Nov 16;2(11):e0283. doi: 10.1097/CCE.0000000000000283. eCollection 2020 Nov.

Abstract

UNLABELLED

To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.

DESIGN

Observational cohort study of patients hospitalized with coronavirus disease 2019 between March 1, 2020, and April 24, 2020. A propensity-matched (1:1) analysis was used to compare patients who received tocilizumab to controls who did not. Competing risk survival analysis was used to determine the primary outcome of time to mortality, and adjusted log-linear and logistic regression for secondary outcomes.

SETTING

Three hospitals within the NYU Langone Health system in New York.

PATIENTS

Consecutive adult patients hospitalized with coronavirus disease 2019.

INTERVENTION

Tocilizumab 400-mg IV once in addition to standard of care or standard of care alone.

MEASUREMENTS AND MAIN RESULTS

Data from 3,580 severe acute respiratory syndrome coronavirus 2 positive qualifying hospitalized patients were included, of whom 497 (13.9%) were treated with tocilizumab. In the analysis of tocilizumab-treated patients and matched controls, fewer tocilizumab-treated patients died (145/497, 29.2%) than did controls (211/497, 42.4%). In the adjusted competing risk regression model, tocilizumab therapy was associated with improved survival relative to controls (hazard ratio = 0.24, 95% CI = 0.18-0.33, < 0.001). Tocilizumab-treated patients and controls had similar adjusted time to discharge from hospital (hazard ratio = 0.96, 95% CI = 0.78-1.17, = 0.67). However, they had longer adjusted ICU length of stay (rate ratio = 3.1, 95% CI = 2.5-3.7, < 0.001) and a higher adjusted infection rate (odds ratio = 4.18, 95% CI = 2.72-6.52, < 0.001) than controls.

CONCLUSIONS

Tocilizumab therapy was associated with significantly improved survival in coronavirus disease 2019 patients. This survival benefit was associated with increased ICU length of stay and increased infection rate, even as more patients in the tocilizumab group were rescued from rapid death. A prospective, randomized, placebo-controlled trial is needed to confirm these findings.

摘要

未标注

为确定抗白细胞介素6受体单克隆抗体托珠单抗对2019冠状病毒病患者生存率的影响。

设计

对2020年3月1日至2020年4月24日期间因2019冠状病毒病住院的患者进行观察性队列研究。采用倾向评分匹配(1:1)分析,比较接受托珠单抗治疗的患者与未接受治疗的对照患者。采用竞争风险生存分析确定至死亡时间的主要结局,并采用调整后的对数线性和逻辑回归分析次要结局。

地点

纽约大学朗格尼健康系统内的三家医院。

患者

因2019冠状病毒病住院的连续成年患者。

干预措施

除标准治疗外,静脉注射一次400mg托珠单抗或仅采用标准治疗。

测量指标和主要结果

纳入了3580例严重急性呼吸综合征冠状病毒2检测呈阳性的符合条件的住院患者的数据,其中497例(13.9%)接受了托珠单抗治疗。在对接受托珠单抗治疗的患者和匹配对照的分析中,接受托珠单抗治疗的患者死亡人数(145/497,29.2%)少于对照患者(211/497,42.4%)。在调整后的竞争风险回归模型中,与对照相比,托珠单抗治疗与生存率提高相关(风险比=0.24,95%置信区间=0.18-0.33,P<0.001)。接受托珠单抗治疗的患者和对照患者的调整后出院时间相似(风险比=0.96,95%置信区间=0.78-1.17,P=0.67)。然而,与对照相比,他们的调整后重症监护病房住院时间更长(率比=3.1,95%置信区间=2.5-3.7,P<0.001),调整后的感染率更高(比值比=4.18,95%置信区间=2.72-6.52,P<0.001)。

结论

托珠单抗治疗与2019冠状病毒病患者生存率显著提高相关。这种生存获益与重症监护病房住院时间延长和感染率增加有关,即使托珠单抗组更多患者从快速死亡中获救。需要进行一项前瞻性、随机、安慰剂对照试验来证实这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f562/7671881/7153b4c3c2bd/cc9-2-e0283-g001.jpg

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