Prognostic Impact of COVID-19 Inflammation Score Response: A Sub-Group Analysis on Critically Ill Patients of the RuxCoFlam Trial

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; <i>p</i> = 0.046) and male gender (OR, 4.76; 95% CI, 1.22-16.67; <i>p</i> = 0.024) were significantly associated with CIS response. Sixty-day survival probability was higher in CIS-responders compared to non-responders (74% vs. 32%; <i>p</i> < 0.001). Multiple Cox regression analysis revealed younger age (10-year difference) (hazard ratio (HR), 0.65; 95% CI, 0.46-0.91; <i>p</i> = 0.012) and CIS response (HR, 0.19; 95% CI, 0.08-0.45; <i>p</i> < 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.