Abstract
Abstract
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