Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis

Abstract

This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82-0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71-0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81-0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70-0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71-0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89-1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events.Trial registration: Clinical Trials Registry India identifier: CTRI/2020/05/025369.The proper registration is PROSPERO: registration number CRD42021294120.

Keywords: COVID-19; meta-analysis; sarilumab; systematic review; tocilizumab.

Figure 1.

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) study flowchart.

Figure 2.

Forest plot of all-cause 28-day mortality. Forest plot showing the risk ratio in mortality between patients treated with IL-6 receptor antagonist compared with standard of care (SOC). Meta-analysis on 17 randomized controlled studies comprising 8455 patients showed that mortality was significantly 11% lower for patients with COVID-19 treated with tocilizumab compared to SOC and not significant but with lowering 19% mortality in patients treated with sarilumab. Abbreviations: CI, confidence interval; M-H, Mantel-Haenszel random-effects; SOC, standard of care.

Figure 3.

Forest plot of progression to invasive mechanical ventilation. Forest plot showing the risk ratio in progression to invasive mechanical ventilation (IMV) between patients treated with tocilizumab compared with standard of care (SOC). Meta-analysis on 9 randomized controlled studies comprising 5507 patients showed that progression to IMV was significantly 21% lower for patients with COVID-19 treated with tocilizumab compared to SOC, and not significantly different in patients treated with sarilumab. Abbreviations: CI, confidence interval; M-H, Mantel-Haenszel random-effects; SOC, standard of care; IMV, invasive mechanical ventilation.

Figure 4.

Forest plot of serious adverse events. Forest plot showing the risk ratio in serious adverse events between patients treated with IL-6 receptor antagonist compared with standard of care (SOC). Meta-analysis on 15 randomized controlled studies comprising 3952 patients showed that serious adverse events was significantly 17% lower for patients with COVID-19 treated with tocilizumab compared to SOC and not significant in patients treated with sarilumab. Abbreviations: CI, confidence interval; M-H, Mantel-Haenszel random-effects; SOC, standard of care.