Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from randomized controlled trials

Abstract

Objective: To assess the efficacy of IL-6 inhibitors compared to standard of care (SOC) in COVID-19 patients.

Data sources: A systematic review of the MEDLINE and Scopus databases (last search: October 8^th, 2021) was performed according to the PRISMA statement.

Study selection: Randomized control trials (RCTs) comparing IL-6 inhibitors to SOC in hospitalized COVID-19 patients were deemed eligible.

Data extraction and synthesis: Individual patient data were extracted from the Kaplan-Meier curves or were obtained from authors of included studies. Additionally, the reviewers independently abstracted data and assessed study quality of each eligible report.

Results: Eleven studies were identified, incorporating 7467 patients (IL-6 inhibitors: 4103, SOC: 3364). IL-6 inhibitors were associated with decreased risk for death compared to SOC at the one-stage meta-analysis (Hazard Ratio [HR]: 0.75, 95% Confidence interval [CI]: 0.69-0.82, p<0.0001) and the two-stage meta-analysis (HR: 0.85, 95%CI: 0.77-0.93, p<0.001, I² = 0.0%). Meta-regression analysis revealed that the difference in OS between the two groups was not influenced by the mean age of patients. At secondary meta-analyses, IL-6 inhibitors were associated with decreased odds for intubation OR:0.74, 95%CI:0.65-0.85, p<0.001, I²=0.0%). IL-6 inhibitors were associated with increased odds for discharge compared to SOC (OR:1.28, 95% CI:1.15-1.42, p<0.001, I²=0.0%).

Conclusions and relevance: This meta-analysis of individual patient data from randomized trials shows that IL-6 inhibitors significantly reduce the risk of death compared to SOC. IL-6 inhibitors are also associated with better outcomes in terms of intubation and discharge rates compared to SOC.

Keywords: COVID-19; Inteleukin-6; SOC.