Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis

Abstract

Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio <200 mmHg. However, tocilizumab showed a longer length of stay when CRP <100 mg/L than the SOC. Conclusion: This meta-analysis demonstrated that tocilizumab has a positive effect on all-cause mortality. It should be cautiously administrated for optimal results and tailored to the patient's eligibility criteria.

Keywords: COVID-19; Severe; critically ill; tocilizumab.

Figure 1.. Study selection.

Figure 2.. Forest plot outcome between SOC group and TCZ group.

A) All-cause mortality event; B) Subgroup CRP >100 mg/L; C) Subgroup PaO2:FiO2 200-300 mmHg; D) Subgroup PaO2:FiO2 <200 mmHg. SOC, standard of care; TCZ, tocilizumab; CRP, C-reactive protein; SD, standard deviation; CI, confidence intervals.

Figure 3.. A forest plot length of stay baseline criteria for administration of tocilizumab CRP < 100 mg/L.

SOC, standard of care; TCZ, tocilizumab; CRP, C-reactive protein; SD, standard deviation; CI, confidence intervals.