Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study.
Effects of tocilizumab on mortality in hospitalized patients with COVID-19: a multicentre cohort study.
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DOI：
10.1016/j.cmi.2020.09.021
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Serrano-Villar S
中科院分区：
文献类型：
--
作者：
Martínez-Sanz J;Muriel A;Ron R;Herrera S;Pérez-Molina JA;Moreno S;Serrano-Villar S
托珠单抗已被提议作为2019年严重冠状病毒病（COVID-19）患者的候选疗法，特别是那些全身炎症较高的患者。我们在一个大型的住院患者队列中调查了接受托珠单抗治疗与死亡率之间的关系。在这项针对西班牙COVID-19住院患者的队列研究中，主要结局是至死亡的时间，次要结局是至入住重症监护室（ICU）或死亡的时间。我们使用逆概率加权来拟合调整时变协变量的边际结构模型，以确定接受托珠单抗治疗与结局之间的因果关系。分析了1229例患者的数据，其中托珠单抗组261例（61例死亡），对照组969例（120例死亡）。在调整的边际结构模型中，检测到托珠单抗治疗与高C反应蛋白（CRP）水平之间存在显著的相互作用。在基线CRP >150 mg/L的患者中，托珠单抗与死亡（校正风险比0.34，95%置信区间0.16-0.72，p 0.005）和ICU入院或死亡（校正风险比0.39，95%置信区间0.19-0.80，p 0.011）风险降低相关，但在CRP ≤ 150 mg/L的患者中不相关。探索性亚组分析得出的点估计值与这些结果一致。在这项大型观察性研究中，托珠单抗与CRP水平较高患者的死亡或ICU入院或死亡风险降低相关。虽然正在进行的托珠单抗在COVID-19患者中的临床试验结果对于确定其安全性和有效性非常重要，但我们的研究结果对未来临床试验的设计具有影响。
Tocilizumab has been proposed as a candidate therapy for patients with severe coronavirus disease 2019 (COVID-19), especially among those with higher systemic inflammation. We investigated the association between receipt of tocilizumab and mortality in a large cohort of hospitalized patients. In this cohort study of patients hospitalized with COVID-19 in Spain, the primary outcome was time to death and the secondary outcome time to intensive care unit (ICU) admission or death. We used inverse probability weighting to fit marginal structural models adjusted for time-varying covariates to determine the causal relationship between receipt of tocilizumab and outcome. Data from 1229 patients were analysed, with 261 patients (61 deaths) in the tocilizumab group and 969 patients (120 deaths) in the control group. In the adjusted marginal structural models, a significant interaction between receipt of tocilizumab and high C-reactive protein (CRP) levels was detected. Tocilizumab was associated with decreased risk of death (adjusted hazard ratio 0.34, 95% confidence interval 0.16–0.72, p 0.005) and ICU admission or death (adjusted hazard ratio 0.39, 95% confidence interval 0.19–0.80, p 0.011) among patients with baseline CRP >150 mg/L but not among those with CRP ≤150 mg/L. Exploratory subgroup analyses yielded point estimates that were consistent with these findings. In this large observational study, tocilizumab was associated with a lower risk of death or ICU admission or death in patients with higher CRP levels. While the results of ongoing clinical trials of tocilizumab in patients with COVID-19 will be important to establish its safety and efficacy, our findings have implications for the design of future clinical trials.
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