Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
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DOI：
10.1016/s2665-9913(20)30277-0
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发表时间：
2020-10-01
影响因子：
25.4
通讯作者：
Goldberg, Stuart L.
中科院分区：
文献类型：
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作者：
Biran, Noa;Ip, Andrew;Goldberg, Stuart L.
Tocilizumab是一种针对白细胞介素-6受体的单克隆抗体，已被提出用于减轻与严重COVID-19相关的细胞因子风暴综合征。我们的目的是调查在COVID-19需要重症监护病房（ICU）支持的患者中，托珠单抗暴露与医院相关死亡率之间的关系。方法在美国新泽西州哈肯萨克子午线健康网络的13家医院进行回顾性观察队列研究。我们纳入了实验室确诊的COVID-19患者（年龄>= 18岁），他们需要在ICU得到支持。我们从前瞻性观察数据库中获得数据，并比较了接受tocilizumab治疗和未接受tocilizumab治疗的患者的结果。我们采用倾向评分匹配的多变量Cox模型来减少混杂效应。主要终点是医院相关死亡率。前瞻性观察数据库已在ClinicalTrials.gov注册，编号NCT04347993。在2020年3月1日至4月22日期间，764名COVID-19患者在ICU需要支持，其中210名（27%）接受了托珠单抗治疗。与接受托珠单抗相关的因素是患者的年龄、性别、肾功能和治疗地点。630例患者纳入倾向评分匹配人群，其中210例接受托珠单抗治疗，420例未接受托珠单抗治疗。630例患者中有358例（57%）死亡，102例（49%）接受tocilizumab治疗，256例（61%）未接受tocilizumab治疗。接受托珠单抗的患者从入院时起的总中位生存期未达到（95% CI为23天-未达到），未接受托珠单抗的患者为19天（16-26天）（风险比[HR] 0.71, 95% CI 0.56-0.89; p=0.0027）。在倾向匹配的主要多变量Cox回归分析中，注意到接受托珠单抗与降低医院相关死亡率之间存在关联（HR 0.64, 95% CI 0.47-0.87; p=0.0040）。在需要机械通气支持和基线c反应蛋白为15mg /dL或更高的亚组中，也注意到与托珠单抗的类似关联。在这项观察性研究中，接受托珠单抗治疗的需要ICU支持的COVID-19患者死亡率降低。正在进行的随机对照试验的结果正在等待中。
Background Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19.Methods We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged >= 18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993.Findings Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days-not reached) among patients receiving tocilizumab and was 19 days (16-26) for those who did not receive tocilizumab (hazard ratio [HR] 0.71, 95% CI 0.56-0.89; p=0.0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0.64, 95% CI 0.47-0.87; p=0.0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher.Interpretation In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited.