Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study

Abstract

To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.

Keywords: ARDS (acute respiratory distress syndrome); COVID-19; JAK inhibitor; SARS-CoV-2; eculizumab.

Figure 1

Clinical outcomes in ruxolitinib and eculizumab treated COVID-19 patients. (A) PaO₂, FiO₂, and PaO₂/FiO₂ ratios are reported for ruxolitinib–eculizumab treated (red lines) and best available therapy (blue lines) subjects at days 0, + 3, and +7. Mean ± SD are shown. (B) D-dimer levels and platelet counts are displayed for treated (red lines) and best available therapy (blue lines) subjects at days 0, + 3, and +7, and platelet counts are compared by unpaired t-test between groups at day +7. Mean ± SD are shown. (C) CT scan imaging at day 0 (Day 0) and after 14 days (Day +14) of ruxolitinib and eculizumab in two representative patients.