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: . The proper registration is PROSPERO: registration number CRD42021294120.

Lethal synergy between SARS-CoV-2 and Streptococcus pneumoniae in hACE2 mice and protective efficacy of vaccination

“…We considered also testing the efficacy of IL-1 and IL-6 neutralization. Recent findings have supported the use of anti-IL-1/IL-1R and anti-IL-6 mAbs in patients with severe COVID-19 (45)(46)(47), and these treatments have been approved by the US Food and Drug Administration for emergency usage in hospitalized patients with COVID-19 with systemic inflammation. Testing the potential of neutralizing these cytokine pathways in combination with GM-CSF administration for prevention of lethality during SARS-CoV-2/S.…”

Inhibiteurs du récepteur de l’IL-6 dans le traitement de la COVID-19 : que savons-nous ?

“…Un bénéfice des inhibiteurs du récepteur de l’IL-6 sur la mortalité brute a été observé dans de nombreux travaux [ [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] ]. Ce bénéfice est présent dans certaines méta-analyses seulement lorsque le modèle statistique utilisé est à effet fixe.…”

Efficacy of tocilizumab in the treatment of COVID‐19: An umbrella review

“…146 Furthermore, research by Yu et al found that sarilumab was not significantly associated with a reduced risk of invasive mechanical ventilation (RR 1.15; 95%CI, 0.38-3.51), whereas tocilizumab reduced the risk by 21% (RR 0.79; 95%CI, 0.71-0.88). 147 The differences between the two may be due to the limited number of studies which have evaluated the effects of sarilumab, compared with tocilizumab, or the different mechanisms of action. Sarilumab blocks IL-6 and IL-6 receptors, but tocilizumab is only an IL-6 receptor antagonist.…”