Systematic Review and Meta-Analysis of Tocilizumab Administration for the Treatment of Hospitalised Patients with COVID-19

Background: Tocilizumab, an IL-6 inhibitor, has been repurposed against the “cytokine storm” in the setting of COVID-19. In this systematic review and meta-analysis, we evaluated the efficacy of tocilizumab in the management of hospitalised COVID-19. Methods: We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalised COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalisation and differences in mortality in ICU and non-ICU patients and in those receiving concomitantly corticosteroids. Findings: We included 52 studies (9 randomised controlled trials (RCTs) and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio, RR, 0.89, 95% CI 0.82 to 0.96; I 2 =0.3%) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83; I 2 =84.0%). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while a non-significant 19% reduction was observed in observational studies (RR 0.81, 95% CI 0.57 to 1.14). Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while there was a trend in favour of the concomitant use in the RCTs. We observed large heterogeneity in data from observational studies and small heterogeneity in RCTs. Interpretation: Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalised patients with moderate to critical COVID-19. Funding Statement: No funding was received for this study. Declaration of Interests: All authors declare no conflict of interest pertaining to this work.