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 2.0 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.

Treatment of severe covid-19 with interleukin 6 receptor inhibition

“…In a linked BMJ Medicine paper (doi:10.1136/bmjmed-2022-000144), Zeraatkar and colleagues conducted a systematic review and network meta-analysis including 36 trials and 19 350 patients to help answer these questions. 4 In their network meta-analysis, Zeraatkar and colleagues combined both direct and indirect comparisons of corticosteroids, tocilizumab, and sarilumab use for severe or critical covid-19. 4 The scope of this study serves to increase the breadth of randomised trial data considered, thus generating more relevant effect estimates than conventional static, pairwise meta-analysis.…”

“…4 In their network meta-analysis, Zeraatkar and colleagues combined both direct and indirect comparisons of corticosteroids, tocilizumab, and sarilumab use for severe or critical covid-19. 4 The scope of this study serves to increase the breadth of randomised trial data considered, thus generating more relevant effect estimates than conventional static, pairwise meta-analysis. The researchers found that, in combination with corticosteroids, tocilizumab probably reduces mortality (odds ratio 0.79, 95% credible interval 0.70 to 0.88, moderate certainty of evidence) and sarilumab could reduce mortality (0.73, 0.58 to 0.92, low certainty of evidence).…”

The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study

“…In the RECOV-ERY trial patients allocated to tocilizumab were more likely to be discharged from the hospital alive within 28 days and had a lower risk of invasive mechanical ventilation or death [21]. Overall, based on the results of REMAP-CAP and RECOVERY trials the use of tocilizumab and sarilumab in combination with dexamethasone was recommended in certain hospitalized patients who are exhibiting rapid respiratory decompensation due to COVID-19 [22].…”

Molecular signaling pathways, pathophysiological features in various organs, and treatment strategies in SARS-CoV2 infection

“…In one systematic review, the role of sarilumab as a potential regimen has been investigated for the treatment of COVID-19 patients, and it has been concluded that sarilumab is a safe and efficient drug with good clinical outcomes ( Chamlagain et al, 2021 ). Also, a network meta-analysis demonstrated that sarilumab and tocilizumab alone or in combination with standard care such as corticosteroids might have similar effects and probably decrease the mortality rate in severe COVID-19 patients ( Zeraatkar et al, 2021 ). In one double-blind and placebo-controlled phase III clinical trial, the efficacy and safety of levilimab have been investigated in severe COVID-19 patients who do not need mechanical ventilation, and it was shown that administration of levilimab combined with standard treatment leads to an enhanced sustained clinical improvement rate ( Lomakin et al, 2021 ).…”