Meta-analysis Of Clinical Efficacy And Safety Of IL-1Ra In Treatment Of COVID-19

Objective:Immunosuppressive agents have attracted much attention as an important therapeutic agent for COVID-19,and interleukin 1 receptor antagonist(IL-1Ra)as one of them is controversial in its efficacy and safety.The representative drugs of IL-1Ra are anakinra and canakinumab.The purpose of this study was to meta analyze the clinical efficacy and safety of IL-1Ra(anakinra/canakinumab)in the treatment of COVID-19,so as to provide evidence-based medical evidence for clinical medication.Methods:PubMed,Embase,the Cochrane Library,CBMdisc,CNKI,Wanfang,VIP and other databases were used to retrieve the published randomized controlled trials(RCTs)of IL-1Ra in the treatment of COVID-19 at home and abroad.The retrieval time was limited to December 2019 to December 2021.After two researchers screened the literature,evaluated the literature quality and extracted the data,then conducted a meta-analysis with Revman5.4 software.Results:After literature search,screening and quality evaluation,a total of 7 RCT studies were included,including five anakinra studies and two canakinumab studies,involving2165 patients with COVID-19,including 1164 in the experimental group and 1001 in the control group.Meta analysis was conducted from the all-cause mortality,28 day clinical improvement rate,incidence of adverse events(AES)and serious adverse events(SAEs)of COVID-19 patients treated with IL-1Ra.The results showed that: 1.Anakinra may slightly increase the clinical improvement rate D28 of COVID-19 patients[RR=1.09,95%CI(1.01,1.18),P=0.04],while the effect of canakinumab on the clinical improvement rate D28 is uncertain[RR=1.05,95%CI(0.98,1.13),P=0.19].2.Compared with the control group,anakinra treatment had no definite effect on all-cause mortality D14 and all-cause mortality D28[RR=0.67,95%CI(0.37,1.20),P=0.18;RR=0.68,95%CI(0.42,1.12),P=0.13],but the all-cause mortality(≥ D60)was slightly higher[RR=1.19,95%CI(1.01,1.40),P=0.04].Canakinumab had no clear effect on all-cause mortality D28[RR=0.75,95%CI(0.39,1.42),P=0.37] and ≥ D60[RR=0.55,95%CI(0.16,1.91),P=0.35 ].3.The relationship between anakinra treatment and the incidence of AEs and SAEs is not clear [ RR=1.03,95%CI(0.95,1.12),P=0.48;RR=0.95,95%CI(0.57,1.56),P=0.83].Similarly,the relationship between canakinumab treatment and the incidence of AEs and SAEs is not clear[RR=1.02,95%CI(0.86,1.21),P=0.85;RR=0.80,95%CI(0.56,1.13),P=0.20].Conclusion:Anakinra may be beneficial to the clinical improvement D28 of moderate and severe COVID-19 patients,but the risk of death(≥ D60)may be slightly increased;Canakinumab had no definite benefit in the clinical improvement D28 and all-cause mortality at all stages;The relationship between COVID-19 treated with the two drugs and the incidence of AES and SAEs is not clear.