Pb2583: ruxolitinib in severe and critical covid19 requiring cpap

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Northern Italy has been one of the first European areas which experienced a major COVID-19 outbreak in 2020. The most common complication triggered by COVID-19 is the acute respiratory distress syndrome often seen in the presence of cytokine storm and immune system hyperactivation, leading to an extremely high mortality rate in older and frail patients. Several immune modulators have been studied in this setting, as well as steroids or interleukin 1 or 6 antagonists. Janus kinase (JAK) – STAT signaling is another critical cellular pathway involved in the inflammatory response. Thus, the JAK 1/2 inhibitor Ruxolitinib, recently approved for the treatment of steroid-refractory graft-versus-host disease, appeared as a promising agent for patients with severe or critical COVID-19. Aims: To assess the clinical impact of Ruxolitinib on patients with severe or critical COVID-19. Methods: We collected data of all COVID-19 patients admitted to the Aosta Valley Regional Hospital, Italy, since the beginning of the pandemic. We restricted the analysis on patients requiring continue positive airway pressure (CPAP) support. Ruxolitinib was given through a compassionate use program (CUP) approved by the Italian National Health Authorities and the Ethics Committee at Spallanzani Hospital in Rome, Italy. Written informed consent was obtained for all patients. We compared the outcome of patients admitted before April the 11th, date of Ruxolitinib availability in our Center, with all patients consequently enrolled in the Ruxolitinib CUP until its closure, on December the 15th 2020. The primary objective of the study was time to recovery, defined as the time from hospital admission to the end of oxygen requirement or discharge, or death for any cause. The 30-day cumulative incidence of recovery comparison was estimated with the Gray test. The impact of variables on outcome was estimated accordingly to the Fine&Gray model for competing risks. The study was performed before COVID-19 vaccines availability. Results: Overall, 178 patients were considered eligible for the analysis, 89 (50%) in the standard of care (SOC) group, 89 (50%) in the Ruxolitinib group. Ruxolitinib was given at the dosage of 5mg BID for 7 days, followed by 3 days of 5mg once a day. The median age of patients in the SOC group was 70.4 (IQR 63.3 - 79.4) years, versus 76.0 (IQR 68.8 – 82.2) years of patients in the Ruxolitinib group (p= 0.005). No statistically significant differences emerged between the two groups among the other variables analyzed, such as gender, comorbidities, COVID-19 symptoms, previous treatment with anti-aggregants or anti-coagulants, chest X-ray Brixia severity score at admission. 30-day cumulative incidence of recovery were 43.8% and 58.8% in SOC group and Ruxolitinib group, respectively (p= 0.0075). When covariates were included in the Fine&Gray model, patients in the Ruxolitinib group showed significantly better time to recovery [Hazard Ratio 1.54 (95%CI 1.05 – 2.26, p= 0.028)]. The propensity score on time to recovery, estimated using multinomial logistic modelling on the same variables used in the covariates adjustment, showed an hazard ratio of 1.91 (95%CI 1.29 – 2.83, p= 0.001) between patients in the Ruxolitinib group compared to SOC. No severe adverse events have been reported in patients treated with Ruxolitinib. Summary/Conclusion: Despite a significantly higher median age, patient with severe and critical COVID-19 requiring CPAP treated with Ruxolitinib showed a significantly better time to recovery and reduced mortality compared to SOC patients, in a single-Center experience. No severe drug-related toxicity has been reported. Ruxolitinib immune-modulating potential should be further explored.Keywords: Adult, Ruxolitinib, Infection, COVID-19