Tocilizumab for COVID-19: A systematic review and meta-analysis of randomized controlled trials

The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I² statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I² value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.