Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study
Combination of Ruxolitinib and Eculizumab for Treatment of Severe SARS-CoV-2-Related Acute Respiratory Distress Syndrome: A Controlled Study
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DOI：
10.3389/fphar.2020.00857
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发表时间：
2020-06-05
影响因子：
5.6
通讯作者：
Selleri, Carmine
中科院分区：
文献类型：
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作者：
Giudice, Valentina;Pagliano, Pasquale;Selleri, Carmine
迄今为止，尚无治疗 COVID-19 的具体治疗策略。基于补体和凝血级联被病毒感染激活，并可能引发急性呼吸窘迫综合征 (ARDS) 的假设，我们报告了连续 17 例 SARS-CoV-2 相关 ARDS 病例的临床结果，这些病例采用鲁索替尼（一种 JAK1/2 抑制剂，10 毫克/每天两次，持续 14 天）和依库丽单抗（一种抗 C5a 补体单克隆抗体，900 毫克）的新型组合治疗。每周静脉注射，最多三周，或采用最佳可用疗法 (N = 10)。与最佳可用治疗组相比，接受联合治疗的患者呼吸道症状和放射学肺部病变显着改善，循环 D-二聚体水平降低。我们的结果支持联合使用鲁索替尼和依库丽珠单抗，通过同时关闭异常的先天性和适应性免疫反应来治疗严重的 SARS-CoV-2 相关 ARDS。
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.