Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.
Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial.
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DOI：
10.1016/s2665-9913(21)00070-9
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
MASH-COVID study group
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文献类型：
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作者：
Cremer PC;Abbate A;Hudock K;McWilliams C;Mehta J;Chang SY;Sheng CC;Van Tassell B;Bonaventura A;Vecchié A;Carey B;Wang Q;Wolski KE;Rajendram P;Duggal A;Wang TS;Paolini JF;Trapnell BC;MASH-COVID study group
在 COVID-19 患者中，粒细胞巨噬细胞集落刺激因子 (GM-CSF) 可能是与呼吸衰竭和死亡相关的过度活跃炎症反应的介质。我们的目的是评估 mavrilimumab（一种针对 GM-CSF 受体的单克隆抗体）是否会改善 COVID-19 肺炎和全身性过度炎症患者的预后。这项由研究者发起的、多中心、双盲、随机试验在美国七家医院进行。纳入需要住院治疗、COVID-19 肺炎、低氧血症和 C 反应蛋白浓度超过 5 mg/dL。如果患者需要机械通气则被排除在外。患者被随机分配（1:1），按医院地点分层，接受马夫利木单抗 6 mg/kg 单次静脉输注或安慰剂。参与者和所有临床和研究人员都不知道治疗分配。主要终点是第 14 天存活和停止补充氧疗的患者比例。主要终点和安全性在意向治疗人群中进行了分析。该试验已在 ClinicalTrials.gov 上注册，编号为 NCT04399980、NCT04463004 和 NCT04492514。 2020年5月28日至9月15日期间，入组了40名患者，并随机分配至mavrilimumab组（n=21）或安慰剂组（n=19）。计划对 60 名患者进行试验，但由于入组缓慢，该研究提前停止，以了解自然史和潜在的治疗效果。第 14 天时，马夫利木单抗组中有 12 名患者 (57%) 存活并停止补充氧疗，而安慰剂组有 9 名患者 (47%)（比值比 1·48 [95% CI 0·43–5·16]；p=0·76）。没有出现与治疗相关的死亡，各组之间的不良事件相似。第 14 天时存活和停止氧疗的患者比例没有显着差异，尽管考虑到宽置信区间，马夫利木单抗治疗对该患者群体的益处或危害仍然可能存在，并且应该完成更大规模的试验。基尼克萨制药公司。
In patients with COVID-19, granulocyte-macrophage colony stimulating factor (GM-CSF) might be a mediator of the hyperactive inflammatory response associated with respiratory failure and death. We aimed to evaluate whether mavrilimumab, a monoclonal antibody to the GM-CSF receptor, would improve outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. This investigator-initiated, multicentre, double-blind, randomised trial was done at seven hospitals in the USA. Inclusion required hospitalisation, COVID-19 pneumonia, hypoxaemia, and a C-reactive protein concentration of more than 5 mg/dL. Patients were excluded if they required mechanical ventilation. Patients were randomly assigned (1:1) centrally, with stratification by hospital site, to receive mavrilimumab 6 mg/kg as a single intravenous infusion, or placebo. Participants and all clinical and research personnel were masked to treatment assignment. The primary endpoint was the proportion of patients alive and off supplemental oxygen therapy at day 14. The primary outcome and safety were analysed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04399980, NCT04463004, and NCT04492514. Between May 28 and Sept 15, 2020, 40 patients were enrolled and randomly assigned to mavrilimumab (n=21) or placebo (n=19). A trial of 60 patients was planned, but given slow enrolment, the study was stopped early to inform the natural history and potential treatment effect. At day 14, 12 (57%) patients in the mavrilimumab group were alive and off supplemental oxygen therapy compared with nine (47%) patients in the placebo group (odds ratio 1·48 [95% CI 0·43–5·16]; p=0·76). There were no treatment-related deaths, and adverse events were similar between groups. There was no significant difference in the proportion of patients alive and off oxygen therapy at day 14, although benefit or harm of mavrilimumab therapy in this patient population remains possible given the wide confidence intervals, and larger trials should be completed. Kiniksa Pharmaceuticals.