COVID-19 Evidence Alerts
from McMaster PLUSTM

Current best evidence for clinical care (more info)

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Treatment Tharmarajah E, Buazon A, Patel V, et al. IL-6 inhibition in the treatment of COVID-19: A meta-analysis and meta-regression. J Infect. 2021 May;82(5):178-185. doi: 10.1016/j.jinf.2021.03.008. Epub 2021 Mar 18.

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: I2 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.

Discipline / Specialty Area Score
Infectious Disease
Hospital Doctor/Hospitalists
Internal Medicine
Intensivist/Critical Care
Comments from MORE raters

Hospital Doctor/Hospitalists rater

Interesting preliminary data.

Infectious Disease rater

Although this well-done meta-analysis with 6778 patients concluded that IL-6 inhibition is associated with a statistically significant reduction in 28-day mortality for patients admitted with COVID-19 (risk ratio 0.9), the 95% confidence interval 0.81 - 0.99 is worrisome.

Internal Medicine rater

As pointed out by the authors, the results of this systematic review/meta-analysis are dependent mostly on one large study.

Respirology/Pulmonology rater

Well done meta-analysis with good discussion of the study limitations. Well balanced discussion.

Respirology/Pulmonology rater

Another meta-analysis that suggests some survival benefit for patients with severe Covid-19 infection treated with IL-6 inhibitors. Most of the data are based on a single trial of 9. The studies utilized were culled from over 2000 reports in the published literature. Optimal treatment for Covid-19 infection remains a moving target.