Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis

Abstract

Objectives Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. Methods A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. Results Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. Conclusion Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.

Tocilizumab Association with Emerging Multi-drug Resistance Organisms and Mortality in critically ill patients with Coronavirus disease 2019 (COVID-19): A Multicenter, Retrospective Cohort Study

“…In one randomized control study comparing tocilizumab with usual care in non ICU COVID-19 patients with moderate to severe pneumonia, there was also no difference in mortality at 28-days (10). Similarly, a recent meta-analysis in ICU patients found no signi cant difference in mortality rates between the tocilizumab group and the comparator groups (24). Alternatively, a previous retrospective cohort study in ICU COVID-19 patients found signi cantly lower ICU mortality in the tocilizumab group but no difference in the 28-day mortality (23).…”

Single Versus Multiple Doses of Tocilizumab in Critically Ill Patients with Coronavirus Disease 2019 (COVID-19): A Two-center, Retrospective Cohort Study

“…Other RCTs also reported no mortality bene ts in patients who received multiple doses of tocilizumab than standard therapy [6], [14]Contrary to that, two large RCTs using one or more tocilizumab doses in critically ill patients with COVID-19 reported improved survival [13], [16], [18], and an increase in the duration of organ support-free days [16]. Moreover, A systemic review and meta-analysis found that tocilizumab use in critically ill patients with COVID-19 reduces mortality and improves patients' outcomes [3]. However, the exact number of patients who received single versus multiple doses was not clearly stated in any previous studies mentioned.…”

“…However, the exact number of patients who received single versus multiple doses was not clearly stated in any previous studies mentioned. Also, none of these studies compared the mortality bene ts between various tocilizumab regimens [3], [16].…”

“…Since the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) emergence, it has affected more than a hundred million individuals and caused more than three million deaths globally [2]. Patients affected with COVID-19 usually manifest with respiratory symptoms ranging from mild to severe pneumonia and acute respiratory distress syndrome (ARDS) [3], [4]. Around 10-15% of patients with moderate to severe symptoms require hospitalization, and up to 5% require intensive care unit (ICU) admission with a mortality rate ranging from 26-38% [5]- [9].…”

“…Since the CRS may induce ARDS, many studies have investigated the off-label use of tocilizumab in patients with COVID-19 pneumonia [6], [12]- [15]. These studies' results about tocilizumab e cacy and safety in critically ill patients are con icting [3], [6], [14]- [17]. Moreover, the dosing regimen of tocilizumab used varied among the previous studies [6], [12], [16]- [18].…”