Tocilizumab and sarilumab alone or in combination with corticosteroids for COVID-19: A systematic review and network meta-analysis

Abstract Objective To compare the effects of interleukin-6 (IL-6) receptor blockers, with or without corticosteroids, on mortality in patients with COVID-19. Design Systematic review and network meta-analysis Data sources WHO COVID-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses Study selection Trials in which people with suspected, probable, or confirmed COVID-19 were randomized to IL-6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. Results We assessed the risk of bias of included trials using a modification of the Cochrane risk of bias tool. We performed a Bayesian fixed effect network meta-analysis and assessed the certainty of evidence using the GRADE approach. We identified 45 eligible trials (20,650 patients), 36 (19,350 patients) of which could be included in the network meta-analysis. 27 of 36 trials were rated at high risk of bias, primarily due to lack of blinding. Tocilizumab (20 more per 1000, 15 fewer to 59 more; low certainty) and sarilumab (11 more per 1000, 38 fewer to 55 more; low certainty) alone may not reduce the risk of death. Tocilizumab, in combination with corticosteroids, probably reduces the risk of death compared to corticosteroids alone (35 fewer per 1000, 52 fewer to 18 more; moderate certainty) and sarilumab, in combination with corticosteroids, may reduce the risk of death compared to corticosteroids alone (43 fewer, 73 fewer to 12 more; low certainty). Tocilizumab and sarilumab, both in combination with corticosteroids, may have similar effects (8 more per 1000, 20 fewer to 35 more; low certainty). Conclusion IL-6 receptor blockers, when added to standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab may have similar effectiveness. Systematic review registration NA What is already known on this topic? IL-6 receptor blockers have immunosuppressive effects that may be important in COVID-19 patients with immune system dysfunction and inflammation Corticosteroids reduce the risk of death in patients with severe or critical COVID-19 What this study adds Our systematic review and network meta-analysis provides a comprehensive review of the evidence addressing the effects of IL-6 receptor blockers, alone or in combination with corticosteroids, in COVID-19 IL-6 receptor blockers when added to a standard care that includes corticosteroids, in patients with severe or critical COVID-19, probably reduce mortality. Tocilizumab and sarilumab in combination with corticosteroids may have similar effectiveness for reducing mortality.