TY - JOUR
T1 - Association between tocilizumab, sarilumab and all-cause mortality at 28 days in hospitalised patients with COVID-19
T2 - A network meta-analysis
AU - Godolphin, Peter J.
AU - Fisher, David J.
AU - Berry, Lindsay R.
AU - Derde, Lennie P.G.
AU - Diaz, Janet V.
AU - Gordon, Anthony C.
AU - Lorenzi, Elizabeth
AU - Marshall, John C.
AU - Murthy, Srinivas
AU - Shankar-Hari, Manu
AU - Sterne, Jonathan A.C.
AU - Tierney, Jayne F.
AU - Vale, Claire L.
N1 - Funding Information:
This study was funded by Prostate Cancer UK in the form of funds to PJG and DJF [RIA 16-ST2-020], by the National Institute for Health Research in the form of funds to PJG [NIHR301653], by the Medical Research Council in the form of funds to DJF, JFT, and CLV [MC_UU_00004/06], by the National Institute for Health Research in the form of funds to MS-H [NIHR-CS-2016-16-011], and by the National Institute for Health Research in the form of funds to ACG [RP-2015-06-018].
Publisher Copyright:
Copyright: © 2022 Godolphin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022/7
Y1 - 2022/7
N2 - 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. 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. 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.
AB - 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. 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. 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.
KW - Adrenal Cortex Hormones/therapeutic use
KW - Antibodies, Monoclonal, Humanized
KW - Humans
KW - Network Meta-Analysis
KW - Prospective Studies
KW - Randomized Controlled Trials as Topic
KW - COVID-19 Drug Treatment
UR - http://www.scopus.com/inward/record.url?scp=85133682891&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0270668
DO - 10.1371/journal.pone.0270668
M3 - Article
C2 - 35802687
AN - SCOPUS:85133682891
SN - 1932-6203
VL - 17
JO - PLoS ONE
JF - PLoS ONE
IS - 7 July
M1 - e0270668
ER -