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Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis

Author

Listed:
  • Peter J Godolphin
  • David J Fisher
  • Lindsay R Berry
  • Lennie P G Derde
  • Janet V Diaz
  • Anthony C Gordon
  • Elizabeth Lorenzi
  • John C Marshall
  • Srinivas Murthy
  • Manu Shankar-Hari
  • Jonathan A C Sterne
  • Jayne F Tierney
  • Claire L Vale

Abstract

Background: A recent prospective meta-analysis demonstrated that interleukin-6 antagonists are associated with lower all-cause mortality in hospitalised patients with COVID-19, compared with usual care or placebo. However, emerging evidence suggests that clinicians are favouring the use of tocilizumab over sarilumab. A new randomised comparison of these agents from the REMAP-CAP trial shows similar effects on in-hospital mortality. Therefore, we initiated a network meta-analysis, to estimate pairwise associations between tocilizumab, sarilumab and usual care or placebo with 28-day mortality, in COVID-19 patients receiving concomitant corticosteroids and ventilation, based on all available direct and indirect evidence. Methods: Eligible trials randomised hospitalised patients with COVID-19 that compared tocilizumab or sarilumab with usual care or placebo in the prospective meta-analysis or that directly compared tocilizumab with sarilumab. Data were restricted to patients receiving corticosteroids and either non-invasive or invasive ventilation at randomisation. Findings: One trial (REMAP-CAP) was identified that directly compared tocilizumab with sarilumab and supplied results on all-cause mortality at 28-days. This network meta-analysis was based on 898 eligible patients (278 deaths) from REMAP-CAP and 3710 eligible patients from 18 trials (1278 deaths) from the prospective meta-analysis. Summary ORs were similar for tocilizumab [0·82 [0·71–0·95, p = 0·008]] and sarilumab [0·80 [0·61–1·04, p = 0·09]] compared with usual care or placebo. The summary OR for 28-day mortality comparing tocilizumab with sarilumab was 1·03 [95%CI 0·81–1·32, p = 0·80]. The p-value for the global test of inconsistency was 0·28. Conclusions: Administration of either tocilizumab or sarilumab was associated with lower 28-day all-cause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.

Suggested Citation

  • Peter J Godolphin & David J Fisher & Lindsay R Berry & Lennie P G Derde & Janet V Diaz & Anthony C Gordon & Elizabeth Lorenzi & John C Marshall & Srinivas Murthy & Manu Shankar-Hari & Jonathan A C Ste, 2022. "Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19: A network meta-analysis," PLOS ONE, Public Library of Science, vol. 17(7), pages 1-13, July.
    • Handle: RePEc:plo:pone00:0270668
    DOI: 10.1371/journal.pone.0270668
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    References listed on IDEAS

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    1. Ian R. White, 2011. "Multivariate random-effects meta-regression: Updates to mvmeta," Stata Journal, StataCorp LLC, vol. 11(2), pages 255-270, June.
    2. Ian R. White, 2015. "Network meta-analysis," Stata Journal, StataCorp LLC, vol. 15(4), pages 951-985, December.
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