Abstract：
OBJECTIVE: To systematically evaluate the efficacy of subcutaneous tocilizumab in the treatment of patients with severe COVID-19 and provide evidence for the rational use of subcutaneous tocilizumab in patients with severe COVID-19.
METHODS: This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched the Cochrane Library, PubMed, Embase, CNKI, SinoMed, and Wanfang Medical Network electronic databases up to 11 January 2023 to identify relevant studies. To obtain the most recent clinical studies of subcutaneous injection of tocilizumab for the treatment of patients with severe COVID-19, we also searched the preprint platforms medRxiv and ChinaXiv. Furthermore, we searched ClinicalTrials.gov for relevant unpublished studies. The studies were screened based on the PICOS principle. The included studies were classified and evaluated for quality based on research type. The RevMan 5.3 software was used to conduct the meta-analysis, and a descriptive analysis was performed to examine relevant outcome indicators.
RESULTS: Five observational studies were obtained, involving a total of 498 patients (240 patients in the subcutaneous injection group and 258 patients in the intravenous injection group). All of the studies were of the highest quality. The meta-analysis of the included studies revealed that the mortality rate of patients who received subcutaneous tocilizumab to treat COVID-19 was not significantly higher than that of the intravenous injection group [23.3% (45/193) vs. 18.4% (39/212), RD = 0.06, 95% CI = - 0.01 ~ 0.13, P = 0.11]. Furthermore, there was no significant difference in the proportion of patients requiring mechanical ventilation between the two groups [24.5% (35/143) vs. 22% (35/159), RD = 0.03, 95% CI = - 0.07 ~ 0.12, P = 0.56].
CONCLUSIONS: The meta-analyses do not provide evidence that subcutaneous and intravenous tocilizumab formulations for the treatment of severe COVID-19 infection differ regarding their effectiveness. Considering that the meta-analyses cannot replace an appropriately powered non-inferiority study, subcutaneous formulations still need to be used with caution and only when intravenous formulations are in short supply. At present, there is a lack of randomized controlled trials of subcutaneous injection of tocilizumab for the treatment of severe COVID-19, and more clinical research should be conducted.
METHODS: This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched the Cochrane Library, PubMed, Embase, CNKI, SinoMed, and Wanfang Medical Network electronic databases up to 11 January 2023 to identify relevant studies. To obtain the most recent clinical studies of subcutaneous injection of tocilizumab for the treatment of patients with severe COVID-19, we also searched the preprint platforms medRxiv and ChinaXiv. Furthermore, we searched ClinicalTrials.gov for relevant unpublished studies. The studies were screened based on the PICOS principle. The included studies were classified and evaluated for quality based on research type. The RevMan 5.3 software was used to conduct the meta-analysis, and a descriptive analysis was performed to examine relevant outcome indicators.
RESULTS: Five observational studies were obtained, involving a total of 498 patients (240 patients in the subcutaneous injection group and 258 patients in the intravenous injection group). All of the studies were of the highest quality. The meta-analysis of the included studies revealed that the mortality rate of patients who received subcutaneous tocilizumab to treat COVID-19 was not significantly higher than that of the intravenous injection group [23.3% (45/193) vs. 18.4% (39/212), RD = 0.06, 95% CI = - 0.01 ~ 0.13, P = 0.11]. Furthermore, there was no significant difference in the proportion of patients requiring mechanical ventilation between the two groups [24.5% (35/143) vs. 22% (35/159), RD = 0.03, 95% CI = - 0.07 ~ 0.12, P = 0.56].
CONCLUSIONS: The meta-analyses do not provide evidence that subcutaneous and intravenous tocilizumab formulations for the treatment of severe COVID-19 infection differ regarding their effectiveness. Considering that the meta-analyses cannot replace an appropriately powered non-inferiority study, subcutaneous formulations still need to be used with caution and only when intravenous formulations are in short supply. At present, there is a lack of randomized controlled trials of subcutaneous injection of tocilizumab for the treatment of severe COVID-19, and more clinical research should be conducted.
摘要：
目的：系统评价托珠单抗皮下治疗重症COVID-19患者的疗效，为临床合理使用托珠单抗治疗重症COVID-19患者提供依据。
方法：本荟萃分析是根据系统评价和荟萃分析（PRISMA）声明的首选报告项目进行的。我们搜查了Cochrane图书馆,PubMed,Embase,CNKI,SinoMed,和万方医疗网电子数据库截至2023年1月11日，以确定相关研究。为了获得皮下注射托珠单抗治疗重症COVID-19患者的最新临床研究，我们还搜索了预印本平台medRxiv和ChinaXiv。此外，我们搜索了ClinicalTrials.gov的相关未发表的研究。这些研究是根据PICOS原理进行筛选的。根据研究类型对纳入的研究进行分类和质量评价。采用RevMan5.3软件进行荟萃分析，并进行描述性分析以检查相关结果指标.
结果：获得了五项观察性研究，共涉及498例患者（皮下注射组240例，静脉注射组258例）。所有的研究都是最高质量的。纳入研究的荟萃分析显示，接受托珠单抗皮下治疗COVID-19的患者死亡率并不明显高于静脉注射组[23.3%(45/193)vs.18.4%（39/212），RD=0.06,95%CI=-0.01~0.13,P=0.11。此外，两组之间需要机械通气的患者比例没有显着差异[24.5％（35/143）与22%（35/159），RD=0.03,95%CI=-0.07~0.12,P=0.56。
结论：荟萃分析没有提供证据表明皮下和静脉内托珠单抗制剂治疗严重COVID-19感染的有效性存在差异。考虑到荟萃分析不能取代适当有力的非劣效性研究，皮下制剂仍然需要谨慎使用，并且仅在静脉内制剂供应短缺时使用。目前,缺乏皮下注射托珠单抗治疗重症COVID-19的随机对照试验,应开展更多的临床研究.
方法：本荟萃分析是根据系统评价和荟萃分析（PRISMA）声明的首选报告项目进行的。我们搜查了Cochrane图书馆,PubMed,Embase,CNKI,SinoMed,和万方医疗网电子数据库截至2023年1月11日，以确定相关研究。为了获得皮下注射托珠单抗治疗重症COVID-19患者的最新临床研究，我们还搜索了预印本平台medRxiv和ChinaXiv。此外，我们搜索了ClinicalTrials.gov的相关未发表的研究。这些研究是根据PICOS原理进行筛选的。根据研究类型对纳入的研究进行分类和质量评价。采用RevMan5.3软件进行荟萃分析，并进行描述性分析以检查相关结果指标.
结果：获得了五项观察性研究，共涉及498例患者（皮下注射组240例，静脉注射组258例）。所有的研究都是最高质量的。纳入研究的荟萃分析显示，接受托珠单抗皮下治疗COVID-19的患者死亡率并不明显高于静脉注射组[23.3%(45/193)vs.18.4%（39/212），RD=0.06,95%CI=-0.01~0.13,P=0.11。此外，两组之间需要机械通气的患者比例没有显着差异[24.5％（35/143）与22%（35/159），RD=0.03,95%CI=-0.07~0.12,P=0.56。
结论：荟萃分析没有提供证据表明皮下和静脉内托珠单抗制剂治疗严重COVID-19感染的有效性存在差异。考虑到荟萃分析不能取代适当有力的非劣效性研究，皮下制剂仍然需要谨慎使用，并且仅在静脉内制剂供应短缺时使用。目前,缺乏皮下注射托珠单抗治疗重症COVID-19的随机对照试验,应开展更多的临床研究.
