Publication date: May 14, 2025
This study aims to identify parameters predicting COVID-19 inflammation score (CIS) response and survival probability in critically ill patients with hyperinflammation treated with the Janus kinase (JAK) 1/2 inhibitor ruxolitinib. This is a single arm, non-randomized, open-label, phase-II study for frontline treatment in adults in the intensive care unit (ICU). Ninety-two critically ill COVID-19 patients with CIS ≥ 10 were treated in the RuxCoFlam trial (NCT04338958) with ruxolitinib between April 2020 and June 2021. Median ICU treatment duration was 15 days (range, 2-73). Out of 81 evaluable patients, 62 (77%) showed CIS reduction ≥ 25% on day 7 (CIS response). In multiple logistic regression analyses, higher CIS on day 0 (odds ratio (OR), 1. 56; 95% confidence interval (CI), 1. 01-2. 41; p = 0. 046) and male gender (OR, 4. 76; 95% CI, 1. 22-16. 67; p = 0. 024) were significantly associated with CIS response. Sixty-day survival probability was higher in CIS-responders compared to non-responders (74% vs. 32%; p < 0. 001). Multiple Cox regression analysis revealed younger age (10-year difference) (hazard ratio (HR), 0. 65; 95% CI, 0. 46-0. 91; p = 0. 012) and CIS response (HR, 0. 19; 95% CI, 0. 08-0. 45; p < 0. 001) as significant parameters for survival probability. In conclusion, reduced risk of death in CIS-responders underlines the usefulness of CIS for the assessment of hyperinflammatory disorders, such as COVID-19, under JAK1/2 inhibitor therapy.
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| Concepts | Keywords |
|---|---|
| Death | COVID-19 |
| June | critically ill |
| Nct04338958 | cytokine storm |
| Therapy | hyperinflammation |
| JAK inhibitors | |
| mortality |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| disease | MESH | Inflammation |
| disease | MESH | Critically Ill |
| drug | DRUGBANK | Ruxolitinib |
| disease | MESH | death |
| disease | MESH | cytokine storm |
| disease | MESH | viral infections |
| drug | DRUGBANK | Baricitinib |
| drug | DRUGBANK | Oxygen |
| drug | DRUGBANK | Nonoxynol-9 |
| disease | MESH | macrophage activation syndrome |
| disease | MESH | splenomegaly |
| disease | MESH | cytopenias |
| disease | MESH | hypertriglyceridemia |
| disease | IDO | blood |
| drug | DRUGBANK | Prothrombin |
| disease | MESH | blood clot |
| drug | DRUGBANK | Aspartame |
| disease | MESH | pneumonia |
| disease | MESH | hypoxia |
| drug | DRUGBANK | Pentaerythritol tetranitrate |
| disease | MESH | hypersensitivity pneumonitis |
| drug | DRUGBANK | Fibrinogen Human |
| disease | IDO | assay |