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Interleukin-6 inhibitors reduce mortality in coronavirus disease-2019: An individual patient data meta-analysis from
Panagiotis T Tasoudis1, Christina K Arvaniti1, Anastasia T Adamou1
1Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Insights
Interleukin-6 (IL-6) inhibitors significantly reduced mortality risk in COVID-19 patients compared to standard of care. These inhibitors also improved outcomes regarding intubation and discharge rates.
Area of Science:
- Infectious Diseases
- Immunology
- Critical Care Medicine
Background:
- COVID-19 is a significant global health concern.
- Cytokine storm, involving Interleukin-6 (IL-6), plays a critical role in COVID-19 pathogenesis.
- Standard of care (SOC) for severe COVID-19 has evolved, but mortality remains high.
Purpose of the Study:
- To evaluate the efficacy of IL-6 inhibitors versus SOC in hospitalized COVID-19 patients.
- To synthesize individual patient data from randomized controlled trials (RCTs).
- To assess the impact of IL-6 inhibitors on mortality, intubation, and discharge rates.
Main Methods:
- Systematic review of MEDLINE and Scopus databases following PRISMA guidelines.
- Inclusion of RCTs comparing IL-6 inhibitors to SOC in hospitalized COVID-19 patients.
- Individual patient data extraction from Kaplan-Meier curves and author correspondence; data abstraction and quality assessment by independent reviewers.
Main Results:
- Eleven studies with 7467 patients were analyzed (IL-6 inhibitors: 4103, SOC: 3364).
- IL-6 inhibitors were associated with a significantly decreased risk of death (one-stage meta-analysis HR: 0.75, 95% CI: 0.69-0.82; two-stage meta-analysis HR: 0.85, 95% CI: 0.77-0.93).
- IL-6 inhibitors showed decreased odds for intubation (OR: 0.74) and increased odds for discharge (OR: 1.28) compared to SOC.
Conclusions:
- IL-6 inhibitors significantly reduce the risk of death in COVID-19 patients compared to standard of care.
- IL-6 inhibitors demonstrate improved outcomes, including lower intubation rates and higher discharge rates.
- These findings support the use of IL-6 inhibitors as an effective treatment strategy for hospitalized COVID-19 patients.
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 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.
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