Tocilizumab in the treatment of COVID-19-a meta-analysis

Background: Interleukin-6 inhibitors showed promising results in observational trials of patients with coronavirus disease 2019 (COVID-19). Aim: To evaluate whether interleukin-6 inhibitor tocilizumab (TCZ) reduces mortality among hospitalized COVID-19 patients. Design: A systematic review and meta-analysis. Methods: Systematic review and meta-analysis of randomized controlled trials (RCTs) comparing TCZ vs. placebo/control, for treatment of adults with COVID-19. Primary outcome was 28-30 days all-cause mortality. Search was conducted up to 1 April 2021. Two independent reviewers screened citations, extracted data and assessed risk of bias. Relative risk (RR) with 95% confidence intervals (CI) were pooled. We performed subgroup analysis for patients with critical illness and sensitivity analyses. Results: Eight RCTs were included, assessing 6481 patients with mostly severe non-critical COVID-19 infection. TCZ was associated with a reduction in all-cause 28-30-day mortality compared to placebo/control (RR=0.89, 95% CI 0.82-0.96). Among the subgroup of critically ill patients no reduced mortality was demonstrated (RR=0.94, 95% CI 0.74-1.19). No mortality benefit with TCZ was demonstrated in trials that used steroids for >80% of patients. TCZ was associated with significantly reduced risk for mechanical ventilation (MV); for combined endpoint of death or MV and for intensive care unit (ICU) admission. No significant difference in adverse events was demonstrated. Risk of serious superinfection was significantly lower with TCZ (RR=0.57, 95% CI 0.35-0.93). Conclusion: The treatment with TCZ reduces 28-30 days all-cause mortality, ICU admission, superinfections, MV and the combined endpoint of death or MV. Among critically ill patients, and when steroids were used for most patients, no mortality benefit was demonstrated. Additional research should further define sub-groups that would benefit most and preferred timing of administration of TCZ in severe COVID-19.

Automated summary

Interleukin-6 inhibitor tocilizumab reduces 28-30 days all-cause mortality, mechanical ventilation risk, ICU admission rate, and superinfection risk in COVID-19 patients. However, no mortality benefit was found in critically ill patients and those who were predominantly treated with steroids. Further research is needed to determine sub-groups that benefit most and the optimal timing of TCZ administration in severe COVID-19.