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托珠单抗对 COVID-19 住院患者死亡率的影响:一项随机对照试验的荟萃分析。

The effect of tocilizumab on mortality in hospitalized patients with COVID-19: a meta-analysis of randomized controlled trials.

机构信息

School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia.

School of Applied Sciences, University of Huddersfield, Huddersfield, United Kingdom.

出版信息

Eur J Clin Pharmacol. 2021 Aug;77(8):1089-1094. doi: 10.1007/s00228-021-03087-z. Epub 2021 Feb 2.

Abstract

OBJECTIVE

We aimed to perform a meta-analysis of randomized controlled trials (RCTs) to summarize the overall effect of tocilizumab on the risk of mortality among patients with coronavirus disease 2019 (COVID-19).

METHODS

We systematically searched PubMed, Cochrane Central Register of Controlled Trials, Google Scholar, and medRxiv (preprint repository) databases (up to 7 January 2021). Pooled effect sizes with 95% confidence interval (CI) were generated using random-effects and inverse variance heterogeneity models. The risk of bias of the included RCTs was appraised using version 2 of the Cochrane risk-of-bias tool for randomized trials.

RESULTS

Six RCTs were included: two trials with an overall low risk of bias and four trials had some concerns regarding the overall risk of bias. Our meta-analysis did not find significant mortality benefits with the use of tocilizumab among patients with COVID-19 relative to non-use of tocilizumab (pooled hazard ratio = 0.83; 95% CI 0.66-1.05, n = 2,057). Interestingly, the estimated effect of tocilizumab on the composite endpoint of requirement for mechanical ventilation and/or all-cause mortality indicated clinical benefits, with some evidence against our model hypothesis of no significant effect at the current sample size (pooled hazard ratio = 0.62; 95% CI 0.42-0.91, n = 749).

CONCLUSION

Despite no clear mortality benefits in hospitalized patients with COVID-19, tocilizumab appears to reduce the likelihood of progression to mechanical ventilation.

摘要

目的

我们旨在进行一项随机对照试验(RCT)的荟萃分析,以总结托珠单抗对 2019 年冠状病毒病(COVID-19)患者死亡风险的总体影响。

方法

我们系统地检索了 PubMed、Cochrane 对照试验中心注册库、Google Scholar 和 medRxiv(预印本存储库)数据库(截至 2021 年 1 月 7 日)。使用随机效应和逆方差异质性模型生成具有 95%置信区间(CI)的汇总效应大小。使用 Cochrane 随机试验风险偏倚工具版本 2 评估纳入 RCT 的风险偏倚。

结果

纳入了六项 RCT:两项试验总体风险偏倚较低,四项试验总体风险偏倚存在一些担忧。我们的荟萃分析没有发现 COVID-19 患者使用托珠单抗相对于不使用托珠单抗在死亡率方面有显著获益(汇总风险比=0.83;95%CI 0.66-1.05,n=2057)。有趣的是,托珠单抗对机械通气和/或全因死亡率复合终点的估计效果表明具有临床获益,有证据表明当前样本量下我们模型假设的无显著效果不成立(汇总风险比=0.62;95%CI 0.42-0.91,n=749)。

结论

尽管 COVID-19 住院患者没有明显的死亡率获益,但托珠单抗似乎降低了进展为机械通气的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eafc/7853160/2a806c29ca90/228_2021_3087_Fig1_HTML.jpg

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