Open Access

Manfred Weiss, Jakob Hammersen, Sebastian Rudolphi, Isabell Formann, Karl Träger, Frank G. Rücker, Beate Grüner, Andreas Allgöwer, Sebastian Birndt, Christian Fabisch, Andreas Hochhaus, Konstanze Döhner, Paul La Rosée, Frank Stegelmann

• 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 toThis 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.…