School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Rev Med Virol. 2022 Nov;32(6):e2388. doi: 10.1002/rmv.2388. Epub 2022 Aug 27.
Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 10 /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.
托珠单抗是一种白细胞介素 (IL)-6 受体抑制剂，已被提议作为治疗 2019 年冠状病毒病 (COVID-19) 的治疗药物。本伞式评价旨在确定托珠单抗治疗 COVID-19 的疗效，并对该主题的所有系统评价进行概述。我们系统地检索了 PubMed、Scopus、Web of Science 集合、Cochrane 图书馆、Epistemonikos 和 Google Scholar，以及 medRxiv 预印本服务器。这些数据库截至 2021 年 9 月 30 日进行了搜索，使用了以下关键字：'SARS-CoV-2'、'COVID-19'、'tocilizumab'、'RHPM-1'、'systematic review' 和'meta-analysis'。如果研究是系统评价（无论是否进行了荟萃分析），调查了托珠单抗在确诊 COVID-19 患者中的疗效或安全性，则将其纳入研究。使用 AMSTAR 2 清单评估纳入文章的质量，同时使用 Egger 检验检查发表偏倚。共纳入 50 项合格的系统评价。汇总估计显示，与对照组相比，接受托珠单抗治疗的患者临床失败（风险比 (RR) 0.75；95%置信区间 (CI)，0.61-0.93）、死亡（RR 0.78；95%CI，0.71-0.85）和需要机械通气（RR 0.77；95%CI，0.64-0.92）的风险显著降低。此外，对于接受托珠单抗治疗的患者，与对照组相比，生存获益也有所增加（调整后的危险比 (aHR) 0.52；95%CI，0.43-0.63）。此外，与对照组相比，托珠单抗治疗组呼吸机脱机天数显著增加（加权均数差 (WMD) 3.38；95%CI，0.51-6.25）。此外，淋巴细胞计数（WMD 0.26×10 /L；95%CI，0.14-0.37）、白细胞介素-6（WMD 176.99 pg/mL；95%CI，76.34-277.64）和 D-二聚体（WMD 741.08 ng/mL；95%CI，109.42-1372.75）在接受托珠单抗治疗的患者中均显著升高。然而，托珠单抗治疗后乳酸脱氢酶（LDH）（WMD -30.88 U/L；95%CI，-51.52，-10.24）和 C 反应蛋白（CRP）（WMD -104.83 mg/L；95%CI，-133.21，-76.46）的水平均显著降低。托珠单抗治疗降低了 COVID-19 患者插管、死亡和住院时间的风险，而不会增加继发感染的风险。因此，托珠单抗可被视为治疗 COVID-19 患者的有效治疗药物。
