Critical care (London, England) · 2026
Evaluating plasma ferritin and suPAR as treatable traits for critically ill patients with COVID-19 treated with anakinra: an exploratory analysis of the immune modulation domain of the REMAP-CAP randomised clinical trial.
СтатьяРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Boyle Andrew J, Ryan Elizabeth G, Berry Lindsay R, Berry Scott, Derde Lennie, Lawler Patrick R, Lorenzi Elizabeth, O'Kane Cecilia M, Shankar-Hari Manu, Veerdonk Frank van de, Gordon Anthony C, McAuley Daniel F, REMAP-CAP Immune Modulation Domain Investigators
Аннотация
BACKGROUND: Identifying treatable traits in critically ill patients offers potential to enable a precision medicine approach to treatment. The aim of this exploratory analysis of the REMAP-CAP immune modulation domain was to evaluate whether plasma ferritin or soluble urokinase plasminogen activator receptor (suPAR) represent treatable traits for anakinra in critically ill patients with coronavirus disease (COVID-19).
METHODS: An exploratory analysis of patients randomised within the COVID-19 immune modulation domain of the REMAP-CAP trial was conducted. Adults within 24 h of receiving respiratory or cardiovascular organ support in an ICU with suspected or microbiologically confirmed COVID-19 were included. Plasma ferritin was measured at study sites, and plasma suPAR measured in stored plasma samples. The primary outcome was organ support-free days (OSFD) until day 21. Analyses were performed using a Bayesian cumulative logistic regression model, and results are presented as the posterior median odds ratio (OR), along with 95% credible intervals (CrI), for anakinra being superior to control.
RESULTS: In ferritin analyses, 1243 patients were included. Patients with increasing ferritin levels had numerically fewer OSFDs. The posterior probabilities of anakinra having benefit (OR > 1) were 64%, 71%, and 21% across increasing ferritin terciles, compared to 53% in analyses that did not adjust for ferritin levels. 145 patients were included in the suPAR analyses. Patients with high baseline plasma suPAR (≥ 6 ng/ml; n = 85) had numerically fewer OSFDs than patients with low plasma suPAR (-1.0 (-1.0, 9.0) vs. 13.0 (-1.0, 17.0)). The posterior probabilities of anakinra having benefit (OR > 1) were 94.8% (OR 2.28 [0.85-6.06]) in patients with low baseline suPAR, and 38.6% (OR 0.88 [0.39-2.00]) in patients with high baseline suPAR.
CONCLUSION: Plasma ferritin does not identify patients with COVID-19 who benefit from treatment with anakinra, whilst anakinra may be beneficial in patients with low, rather than high, baseline plasma suPAR. These hypothesis-generating findings contrast with the results of clinical trials in non-critically ill patients with COVID-19.
TRIAL REGISTRATION: NCT02735707. Date of trial registration: 06/04/2016.
METHODS: An exploratory analysis of patients randomised within the COVID-19 immune modulation domain of the REMAP-CAP trial was conducted. Adults within 24 h of receiving respiratory or cardiovascular organ support in an ICU with suspected or microbiologically confirmed COVID-19 were included. Plasma ferritin was measured at study sites, and plasma suPAR measured in stored plasma samples. The primary outcome was organ support-free days (OSFD) until day 21. Analyses were performed using a Bayesian cumulative logistic regression model, and results are presented as the posterior median odds ratio (OR), along with 95% credible intervals (CrI), for anakinra being superior to control.
RESULTS: In ferritin analyses, 1243 patients were included. Patients with increasing ferritin levels had numerically fewer OSFDs. The posterior probabilities of anakinra having benefit (OR > 1) were 64%, 71%, and 21% across increasing ferritin terciles, compared to 53% in analyses that did not adjust for ferritin levels. 145 patients were included in the suPAR analyses. Patients with high baseline plasma suPAR (≥ 6 ng/ml; n = 85) had numerically fewer OSFDs than patients with low plasma suPAR (-1.0 (-1.0, 9.0) vs. 13.0 (-1.0, 17.0)). The posterior probabilities of anakinra having benefit (OR > 1) were 94.8% (OR 2.28 [0.85-6.06]) in patients with low baseline suPAR, and 38.6% (OR 0.88 [0.39-2.00]) in patients with high baseline suPAR.
CONCLUSION: Plasma ferritin does not identify patients with COVID-19 who benefit from treatment with anakinra, whilst anakinra may be beneficial in patients with low, rather than high, baseline plasma suPAR. These hypothesis-generating findings contrast with the results of clinical trials in non-critically ill patients with COVID-19.
TRIAL REGISTRATION: NCT02735707. Date of trial registration: 06/04/2016.