Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis.
Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis.
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DOI：
10.1016/j.cmi.2020.10.036
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Kashour T
中科院分区：
文献类型：
--
作者：
Tleyjeh IM;Kashour Z;Damlaj M;Riaz M;Tlayjeh H;Altannir M;Altannir Y;Al-Tannir M;Tleyjeh R;Hassett L;Kashour T
细胞因子释放综合征伴白细胞介素-6（IL-6）水平升高与2019年严重冠状病毒病（COVID-19）的多器官损伤和死亡相关。我们的目的是对关于IL-6受体拮抗剂托珠单抗在COVID-19患者中的疗效和毒性的文献进行一项实时系统综述。数据来源为奥维德MEDLINE（R）和Epub Ahead of Print、In-Process & Other Non-Indexed Citations和Daily、奥维德Embase、奥维德Cochrane对照试验中心登记处、奥维德科克伦系统评价数据库、Web of Science、Scopus up、预印本服务器和Google，截至2020年10月8日。研究资格标准是随机对照试验（RCT）和低或中度偏差风险的观察性研究。参与者是住院的COVID-19患者。干预措施包括托珠单抗与安慰剂或标准治疗。我们分别汇总了随机对照试验的粗风险比（RR）和队列的调整后RR。我们评估了I2研究之间的不一致性。我们使用GRADE方法评估证据的确定性。在1156篇引文中，24项研究符合条件（5项RCT和19个队列）。5项低偏倚风险的随机对照试验，共1325例患者，研究了托珠单抗对短期死亡率的影响;合并RR为1.09（95%CI 0.80-1.49，I2 = 0%）。4项随机对照试验（RCT）共纳入771例患者，研究了托珠单抗对机械通气风险的影响;合并RR为0.71（95%CI 0.52-0.96，I2 = 0%），需要治疗的相应数量为17例（95%CI 9-100）。在18个有中度偏倚风险的队列（9850例患者）中，死亡率的合并校正RR为0.58（95%CI 0.51-0.66，I2 = 2.5%）。在所有COVID-19严重程度上都观察到了这种关联。来自随机对照试验的数据并未显示托珠单抗的感染或不良事件风险更高：合并RR分别为0.63（95%CI 0.38-1.06，5项随机对照试验）和0.83（95%CI 0.55-1.24，5项随机对照试验）。累积的中等确定性证据显示，托珠单抗可降低住院COVID-19患者的机械通气风险。虽然RCT显示托珠单抗不能降低短期死亡率，但队列研究的低确定性证据表明托珠单抗与较低死亡率之间存在关联。我们没有观察到使用托珠单抗的感染或不良事件风险更高。本综述将持续评估托珠单抗在COVID-19治疗中的作用。
Cytokine release syndrome with elevated interleukin-6 (IL-6) levels is associated with multiorgan damage and death in severe coronavirus disease 2019 (COVID-19). Our objective was to perform a living systematic review of the literature concerning the efficacy and toxicity of the IL-6 receptor antagonist tocilizumab in COVID-19 patients. Data sources were Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus up, preprint servers and Google up to October 8, 2020. Study eligibility criteria were randomized controlled trials (RCTs) and observational studies at low or moderate risk of bias. Participants were hospitalized COVID-19 patients. Interventions included tocilizumab versus placebo or standard of care. We pooled crude risk ratios (RRs) of RCTs and adjusted RRs from cohorts, separately. We evaluated inconsistency between studies with I2. We assessed the certainty of evidence using the GRADE approach. Of 1156 citations, 24 studies were eligible (five RCTs and 19 cohorts). Five RCTs at low risk of bias, with 1325 patients, examined the effect of tocilizumab on short-term mortality; pooled RR was 1.09 (95%CI 0.80–1.49, I2 = 0%). Four RCTs with 771 patients examined the effect of tocilizumab on risk of mechanical ventilation; pooled RR was 0.71 (95%CI 0.52–0.96, I2 = 0%), with a corresponding number needed to treat of 17 (95%CI 9–100). Among 18 cohorts at moderate risk of bias with 9850 patients, the pooled adjusted RR for mortality was 0.58 (95%CI 0.51–0.66, I2 = 2.5%). This association was observed over all degrees of COVID-19 severity. Data from the RCTs did not show a higher risk of infections or adverse events with tocilizumab: pooled RR 0.63 (95%CI 0.38–1.06, five RCTs) and 0.83 (95%CI 0.55–1.24, five RCTs), respectively. Cumulative moderate-certainty evidence shows that tocilizumab reduces the risk of mechanical ventilation in hospitalized COVID-19 patients. While RCTs showed that tocilizumab did not reduce short-term mortality, low-certainty evidence from cohort studies suggests an association between tocilizumab and lower mortality. We did not observe a higher risk of infections or adverse events with tocilizumab use. This review will continuously evaluate the role of tocilizumab in COVID-19 treatment.
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影响因子：
25.4
作者：
Guaraldi, Giovanni;Meschiari, Marianna;Mussini, Cristina
通讯作者：
Mussini, Cristina
影响因子：
158.5
作者：
Benson, K;Hartz, AJ
通讯作者：
Hartz, AJ
DOI：
10.1016/0197-2456(86)90046-2
发表时间：
1986-09-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
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作者：
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通讯作者：
LAIRD, N
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作者：
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通讯作者：
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影响因子：
25.4
作者：
De Luca, Giacomo;Cavalli, Giulio;Dagna, Lorenzo
通讯作者：
Dagna, Lorenzo