Abstract / Description of output
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 allcause mortality 28 days after randomisation were estimated using a frequentist contrastbased 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 allcause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.
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 allcause mortality 28 days after randomisation were estimated using a frequentist contrastbased 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 allcause mortality compared with usual care or placebo. The association is not dependent on the choice of interleukin-6 receptor antagonist.
| Original language | English |
|---|---|
| Article number | e0270668 |
| Number of pages | 13 |
| Journal | PLoS ONE |
| Volume | 17 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 8 Jul 2022 |