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 8th, 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 OR0.74, 95%CI0.65-0.85, p<0.001, I2=0.0%). IL-6 inhibitors were associated with increased odds for discharge compared to SOC (OR1.28, 95% CI1.15-1.42, 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.