GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study
GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study
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DOI：
10.1016/s2665-9913(20)30170-3
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发表时间：
2020-08-01
影响因子：
25.4
通讯作者：
Dagna, Lorenzo
中科院分区：
文献类型：
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作者：
De Luca, Giacomo;Cavalli, Giulio;Dagna, Lorenzo
背景COVID-19肺炎和全身性炎症过度患者的死亡率很高。我们的目的是检查在标准治疗中加入抗粒细胞-巨噬细胞集落刺激因子受体α单克隆抗体mavrilimumab是否能改善COVID-19肺炎和全身性炎症过度患者的临床结局。方法这项单中心前瞻性队列研究包括18岁或以上的患者，他们在San Raffaele医院住院（米兰，意大利），患有严重的COVID-19肺炎、缺氧和全身性炎症过度。患者接受单次静脉内剂量（6 mg/kg）的mavrilimumab，添加到当时医院提供的标准护理中。对照组由在同一家医院接受标准治疗的具有相似基线特征的同期患者组成。主要结局是至临床改善的时间（定义为临床状态七分制量表上两个或更多分的改善）。其他结果包括实现临床改善的患者比例、生存率、无机械通气生存率和发热消退时间。在2020年3月17日至4月15日期间，13名非机械通气患者（中位年龄57岁[IQR 52 - 58]，12名[92%]男性）接受了mavrilimumab，对照组中的26名患者（中位年龄60岁[IQR 53 - 67]，17名[65%]男性）接受了标准治疗。在28天的随访期间，mavrilimumab组没有患者死亡，对照组有7例（27%）患者死亡（p = 0.086）。在第28天，马威利姆单抗组的所有患者和对照组的17名（65%）患者显示出临床改善（p = 0.030），马威利姆单抗组的改善早于对照组（平均改善时间为8天[IQR 5至11] vs 19天[IQR 11至> 28]，p = 0.0001）。到第28天，mavrilimumab组中有1例（8%）患者进展为机械通气，而对照组中有9例（35%）患者进展为机械通气或死亡（p = 0.14）。到第14天，马威利姆单抗组11例发热患者中有10例（91%）发热消退，而对照组18例发热患者中有11例（61%）发热消退（p = 0.18）;与对照组相比，马威利姆单抗接受者的发热消退更快（中位消退时间为1天[IQR 1至2] vs 7天[3至> 14]，p = 0.0093）。Mavrilimumab耐受性良好，无输注反应。对照组中有3例（12%）患者出现感染并发症。解释在患有严重COVID-19肺炎和全身性炎症过度的非机械通气患者中，与标准治疗相比，Mavrilimumab治疗与改善的临床结局相关。治疗耐受性良好。有效性的确认需要受控测试。版权所有（C）2020爱思唯尔有限公司保留所有权利。
Background Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte-macrophage colony-stimulating factor receptor-alpha monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation.Methods This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily.Findings Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52-58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53-67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0.086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0.030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0.0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0.14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0.18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0.0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications.Interpretation Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Copyright (C) 2020 Elsevier Ltd. All rights reserved.