The effect of tocilizumab on COVID-19 patient mortality: A systematic review and meta-analysis of randomized controlled trials

Lin, Wei-Ting; Hung, Shun-Hsing; Lai, Chih-Cheng; Wang, Cheng-Yi; Chen, Chao-Hsien

Objectives This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of tocilizumab for treating patients with COVID-19. Methods The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and the preprint server of medRxiv.org were searched from their inception to February 20, 2021. Only RCTs that compared the treatment efficacy and safety of tocilizumab with the placebo or the standard of care for adult patients with COVID-19 were included in this meta-analysis. The primary outcome was 28-day mortality. Results This meta-analysis included eight RCTs which enrolled a total of 6,314 patients for randomization, in which 3,267 and 3,047 patients were assigned to the tocilizumab and control groups, respectively. The mortality at day 28 was 24.4% and 29.9% in patients in the tocilizumab and control groups, respectively, meaning there was no significant difference observed between these two groups (OR, 0.92; 95% CI, 0.66-1.28; I2 = 62). This finding did not change in the subgroup analysis according to the initial use of MV or steroid while enrollment. The patients receiving tocilizumab had a lower rate of mechanical ventilation (MV) and intensive care unit (ICU) admission at day 28 compared with the control group (MV use: OR, 0.75; 95% CI, 0.62-0.90; I2 = 11; ICU admission: OR, 0.51; 95% CI, 0.28-0.92; I2 = 30). There were no significant differences between these two treatment groups in terms of the risk of treatment-emergent adverse events (AEs) (OR, 1.03; 95% CI, 0.71-1.49; I2 = 43), serious AEs (OR, 0.86; 95% CI, 0.67-1.12; I2 = 0) or infection (OR, 0.87; 95% CI, 0.63-1.20; I2 = 0). Conclusions Tocilizumab does not provide a survival benefit for patients with COVID-19, but it may help reduce the risk of MV and ICU admission. In addition, tocilizumab is a safe agent to use for the treatment of COVID-19.