Efficacy and safety of IL-6 inhibitors in patients with COVID-19 pneumonia: a systematic review and meta-analysis of multicentre, randomized trials

Abstract

Abstract Purpose COVID-19 is characterized by dysregulated immune response, respiratory failure and a relevant mortality rate among hospitalized patients. Interleukin-6 (IL-6) is involved in COVID-19-associated cytokine storm, and several trials investigated whether its inhibition could improve patients’ outcome. We performed a meta-analysis of randomized trials (RCT) to test this hypothesis. Materials and methods Two independent investigators searched PubMed, Scopus, ClnicalTrials.gov and medRxiv up to September 1st, 2021. Inclusion criteria were: administration of tocilizumab or sarilumab; COVID-19 adult patients with pneumonia; and being a RCT. Primary outcome was mortality at the longest follow-up. Secondary outcomes included intubation rate and incidence of adverse events. Two independent investigators extracted data from eligible trials. Results Of the 763 studies assessed, 15 RCTs were included (9,320 patients), all were multicentre, and the majority open-label vs standard treatment. IL-6 inhibitors were associated with reduced all-cause mortality at the longest follow-up (1315/5,380 [24.4%] in the IL-6 inhibitors group versus 1080/3,814 [28.3%] in the control group, RR = 0.90; 95% CI 0.84 to 0.96; p for effect = 0.003, I2 = 0%, with 13 studies included), with reduction in 28/30-day mortality and intubation rates, and with no increase in adverse events and secondary infections. Conclusion IL-6 inhibitors reduced longest follow-up mortality and intubation in COVID-19 patients. Findings need to be confirmed in high-quality RCTs.