Eculizumab as an emergency treatment for adult patients with severe COVID-19 in the intensive care unit: A proof-of-concept study.
Eculizumab as an emergency treatment for adult patients with severe COVID-19 in the intensive care unit: A proof-of-concept study.
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DOI：
10.1016/j.eclinm.2020.100590
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发表时间：
2020-11
影响因子：
15.1
通讯作者：
Garches COVID 19 Collaborative Group
中科院分区：
文献类型：
--
作者：
Annane D;Heming N;Grimaldi-Bensouda L;Frémeaux-Bacchi V;Vigan M;Roux AL;Marchal A;Michelon H;Rottman M;Moine P;Garches COVID 19 Collaborative Group
抑制补体途径可能对新冠肺炎等病毒感染引起的严重急性呼吸道疾病有利。我们介绍了补体C5抑制剂eculizumab治疗重症新冠肺炎的非随机概念验证研究的结果。纳入2020年3月10日至5月5日期间入住我们重症监护病房的所有确诊为SARS-CoV-2感染和严重新冠肺炎的患者(N=1080)。45名患者接受了标准护理，35名患者接受了标准护理加Eulizumab通过扩大准入的紧急治疗。预先指定的主要结果是第15天的存活率。临床化验值和生物标记物、补体水平和治疗紧急严重不良事件(TESAE)也被评估。在第15天，使用eculizumab的估计存活率为82.9%(95%CI：70.4%~95.3%)，而不使用eculizumab的估计存活率为62.2%(48.1%~76.4%)(对数等级检验，P=0.04)。接受eculizumab治疗的患者与未接受eculizumab治疗的患者相比，乳酸盐、血尿素氮、总胆红素和结合胆红素水平的下降明显更快，而血小板计数、凝血酶原时间和动脉血氧分压/吸入氧分数的比率上升明显更快。与Eculizumab相关的补体水平、实验室数值和生物标志物的变化与终末补体抑制、减少缺氧和减轻炎症是一致的。在接受Eulizumab或不接受Eulizumab治疗的患者中，有5%的患者发生了特别感兴趣的TESAE，包括呼吸机相关性肺炎(51%/24%)、菌血症(11%/2%)、胃十二指肠出血(14%/16%)和溶血(3%/18%)。这项概念验证研究的结果表明，eculizumab可以提高重度新冠肺炎患者的存活率，减少缺氧。评估这种治疗方法的有效性和安全性的随机研究是必要的。投资大道方案：ANR-18-RHUS60004。
Complement pathway inhibition may provide benefit for severe acute respiratory illnesses caused by viral infections such as COVID-19. We present results from a nonrandomized proof-of-concept study of complement C5 inhibitor eculizumab for treatment of severe COVID-19. All patients (N = 80) with confirmed SARS-CoV-2 infection and severe COVID-19 admitted to our intensive care unit between March 10 and May 5, 2020 were included. Forty-five patients were treated with standard care and 35 with standard care plus eculizumab through expanded-access emergency treatment. The prespecified primary outcome was day-15 survival. Clinical laboratory values and biomarkers, complement levels, and treatment-emergent serious adverse events (TESAEs) were also assessed. At day 15, estimated survival was 82.9% (95% CI: 70.4%‒95.3%) with eculizumab and 62.2% (48.1%‒76.4%) without eculizumab (log-rank test, P = 0.04). Patients treated with eculizumab experienced a significantly more rapid decrease in lactate, blood urea nitrogen, total and conjugated bilirubin levels and a significantly more rapid increase in platelet count, prothrombin time, and in the ratio of arterial oxygen tension over fraction of inspired oxygen versus patients treated without eculizumab. Eculizumab-associated changes in complement levels, laboratory values, and biomarkers were consistent with terminal complement inhibition, reduced hypoxia, and decreased inflammation. TESAEs of special interest occurring in >5% of patients treated with/without eculizumab were ventilator-associated pneumonia (51%/24%), bacteremia (11%/2%), gastroduodenal hemorrhage (14%/16%), and hemolysis (3%/18%). Findings from this proof-of-concept study suggest eculizumab may improve survival and reduce hypoxia in patients with severe COVID-19. Randomized studies evaluating the efficacy and safety of this treatment approach are needed. Programme d'Investissements d'Avenir: ANR-18-RHUS60004.
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影响因子：
8.1
作者：
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通讯作者：
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影响因子：
64.8
作者：
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影响因子：
158.5
作者：
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影响因子：
120.7
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LEGALL, JR;LEMESHOW, S;SAULNIER, F
通讯作者：
SAULNIER, F