JAK抑制剂治疗中重度COVID-19患者临床疗效及安全性的Meta分析

Meta-analysis of clinical efficacy and safety of JAK inhibitors in patients with moderate to severe COVID-19

目的:采用Meta分析方法评估JAK抑制剂治疗中重度COVID-19患者的临床疗效及安全性。方法:从PubMed、Web of Science,Cochrane Library数据库检索了2020年1月1日至2022年4月的685篇相关文章,最终纳入13篇文献到RevMan 5.4.1软件中进行主要临床结局的研究。Cochrane风险评估工具和Newcastle-Ottawa Scale(NOS)量表分别评估随机对照实验和队列研究的文献质量。亚组分析研究了用药剂量、种类、合并用药对临床死亡率的影响。结果:最终纳入13项研究,包括4402名患者,大多为感染SARS-CoV-2的中重度或重度老年患者。研究全因死亡率时,实验组与对照组相比有更低的临床死亡风险(RR=0.55,95%CI:0.47~0.65),且实验组总体严重不良反应风险和机械通气的需求率均低于对照组(总体严重不良反应:RR=0.78,95%CI:0.67~0.91;机械通气:RR=0.63,95%CI:0.46~0.85)。按照系统分析了实验组和对照组发生严重不良反应的差异。实验组发生继发性感染、泌尿系统和呼吸系统严重不良事件的风险更低,心血管系统严重不良事件的发生风险差异无统计学意义。此外对用药种类、剂量、合并用药进行了亚组分析,希望对临床治疗提供更多思路。结论:JAK抑制剂治疗中重度或重度COVID-19患者的临床疗效及安全性较好,且临床严重不良事件的发生风险更低,尚无试验证明相关不良反应发生与JAK抑制剂的直接相关性。

OBJECTIVE To assess clinical efficacy and safety of JAK inhibitors in treating moderate to severe COVID-19 patients by a meta-analysis.METHODS This study retrieved 685 relevant articles from the PubMed,Web of Science,and Cochrane Library databases between January 1,2020 and April 20,2022,and 13 literature were included in the RevMan 5.4.1 to examine the safety and therapeutic effectiveness of JAK inhibitors in patients with moderate to severe COVID-19.The Cochrane risk assessment tool and the Newcastle-Ottawa scale(NOS)were used to evaluate the quality of randomized controlled trials and cohort studies.The effects of dosage and mode of medication on clinical mortality were analyzed in the subgroup.RESULTS Totally 13 studies were eventually included,and 4402 patients were enrolled,most were elderly patients with moderately severe or severe SARS-CoV-2 infection.When all-cause mortality was studied,the experimental group had a lower clinical mortality risk than the control group(RR=0.55,95%CI:0.47-0.65).Moreover,the overall risk of severe adverse reactions and the need for mechanical ventilation in the experimental group were lower than those in the control group(overall adverse severe reactions:RR=0.78,95%CI:0.67-0.91;mechanical ventilation:RR=0.63,95%CI:0.46-0.85).We also systematically analyzed the differences in severe adverse reactions between the experimental and control groups.The experimental group had lower risks of secondary infections,and severe adverse reactions to urinary system and respiratory system,but there was no significant difference in the risk of cardiovascular system between the two groups.In addition,a subgroup analysis was conducted on the types of drugs,doses,and concomitant drugs,so as to provide more ideas for clinical treatment.CONCLUSION The clinical efficacy and safety of JAK inhibitors in treating patients with moderate to severe or severe COVID-19 are promising with lower risks of related clinical serious adverse events.No test has demonstrated a direct correlation between the occurrence of related adverse effects and JAK inhibitors yet.