IL-6 inhibition in the treatment of COVID-19: a meta-analysis and meta-regression

Emmanuel Tharmarajah, April Buazon, Vishit Patel, Jennifer R Hannah, Maryam Adas, Victoria B Allen, Katie Bechman, Benjamin D Clarke, Deepak Nagra, Sam Norton, Mark D Russell, Andrew I Rutherford, Mark Yates, James B Galloway

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Objectives: Multiple RCTs of interleukin-6 (IL-6) inhibitors in COVID-19 have been published, with conflicting conclusions. We performed a meta-analysis to assess the impact of IL-6 inhibition on mortality from COVID-19, utilising meta-regression to explore differences in study results. Methods: Systematic database searches were performed to identify RCTs comparing IL-6 inhibitors (tocilizumab and sarilumab) to placebo or standard of care in adults with COVID-19. Meta-analysis was used to estimate the relative risk of mortality at 28 days between arms, expressed as a risk ratio. Within-study mortality rates were compared, and meta-regression was used to investigate treatment effect modification. Results: Data from nine RCTs were included. The combined mortality rate across studies was 19% (95% CI: 18, 20%), ranging from 2% to 31%. The overall risk ratio for 28-day mortality was 0.90 (95% CI: 0.81, 0.99), in favour of benefit for IL-6 inhibition over placebo or standard of care, with low treatment effect heterogeneity: I 2 0% (95% CI: 0, 53%). Meta-regression showed no evidence of treatment effect modification by patient characteristics. Trial-specific mortality rates were explained by known patient-level predictors of COVID-19 outcome (male sex, CRP, hypertension), and country-level COVID-19 incidence. Conclusions: IL-6 inhibition is associated with clinically meaningful improvements in outcomes for patients admitted with COVID-19. Long-term benefits of IL-6 inhibition, its effectiveness across healthcare systems, and implications for differing standards of care are currently unknown.

Original languageEnglish
Pages (from-to)178-185
Number of pages8
JournalJournal of Infection
Volume82
Issue number5
Early online date18 Mar 2021
DOIs
Publication statusPublished - May 2021

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