Boppana Tarun Krishna, Mittal Saurabh, Madan Karan, Mohan Anant, Hadda Vijay, Guleria Randeep
Department of Pulmonary, Critical Care and Sleep Medicine, All India Institute of Medical Sciences (AIIMS), New Delhi.
Monaldi Arch Chest Dis. 2022 Feb 4;92(4). doi: 10.4081/monaldi.2022.2136.
The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.
需要有效的2019冠状病毒病（COVID-19）治疗方法。由于死亡的主要原因是过度炎症状态，白细胞介素-6拮抗剂托珠单抗已在多项临床研究中使用。我们进行了这项系统评价和荟萃分析，以评估托珠单抗降低COVID-19所致死亡率的有效性。对PubMed和Embase数据库进行了系统检索，以提取关于使用托珠单抗治疗COVID-19的随机对照试验（RCT）。进行了总体合并死亡率分析，并报告了比值比。使用Cochrane偏倚风险评估工具评估偏倚风险。使用I2统计量评估异质性。选择了9项RCT（包括6489例患者）进行荟萃分析。7项试验报告了28天死亡率，各有1项试验报告了21天和30天死亡率。在随机分配至类固醇组的3358名参与者中有846人死亡，而在随机分配至对照组的3131名患者中有943人死亡（随机效应比值比0.87，95%置信区间0.73-1.03，p=0.11）。试验之间存在一定异质性，I2值为15%，p值为0.31。托珠单抗组入住重症监护病房（ICU）的需求有所减少。托珠单抗组继发性感染风险较高（固定效应比值比0.72，95%置信区间0.55-0.95，p=0.02）。这项RCT的荟萃分析表明，使用托珠单抗与降低COVID-19患者的全因死亡率无关，且继发性感染几率更高。
