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

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 sari...

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Veröffentlicht in:PloS one Jg. 17; H. 7; S. e0270668
Hauptverfasser: Godolphin, Peter J., Fisher, David J., Berry, Lindsay R., Derde, Lennie P. G., Diaz, Janet V., Gordon, Anthony C., Lorenzi, Elizabeth, Marshall, John C., Murthy, Srinivas, Shankar-Hari, Manu, Sterne, Jonathan A. C., Tierney, Jayne F., Vale, Claire L.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 08.07.2022
Public Library of Science (PLoS)
Schlagworte:
Adrenal Cortex Hormones - therapeutic use
Antibodies, Monoclonal, Humanized
Bias
Biology and Life Sciences
Clinical trials
Computer and Information Sciences
Coronaviruses
Corticoids
Corticosteroids
COVID-19
COVID-19 Drug Treatment
Cytokines
Extracorporeal membrane oxygenation
Fatalities
Health aspects
Health risks
Humans
Interleukin 6
Medicine and Health Sciences
Meta-analysis
Monoclonal antibodies
Mortality
Patients
Physical Sciences
Placebos
Prospective Studies
Randomization
Randomized Controlled Trials as Topic
Research and Analysis Methods
Review boards
Steroids
Ventilation
Ventilators
United Kingdom
ISSN:1932-6203, 1932-6203
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Zusammenfassung: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. 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. Pairwise associations between tocilizumab, sarilumab and usual care or placebo for all-cause mortality 28 days after randomisation were estimated using a frequentist contrast-based network meta-analysis of odds ratios (ORs), implementing multivariate fixed-effects models that assume consistency between the direct and indirect evidence. 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. 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.
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Competing Interests: LPGD is a member of the COVID-19 guideline committee for the Society of Critical Care Medicine/European Society of Intensive Care Medicine/Surviving Sepsis Campaign. ACG has received personal fees from Thirty Respiratory Ltd and GlaxoSmithKline. JCM received personal fees from AM Pharma (for serving as the chair of a data and safety monitoring board), Gilead (for serving as a consultant), and Critical Care Medicine (for serving as associate editor). This does not alter our adherence to PLOS ONE policies on sharing data and materials.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0270668