Cremer Paul C, Abbate Antonio, Hudock Kristin, McWilliams Carla, Mehta Jinesh, Chang Steven Y, Sheng Calvin C, Van Tassell Benjamin, Bonaventura Aldo, Vecchié Alessandra, Carey Brenna, Wang Qiuqing, Wolski Katherine E, Rajendram Prabalini, Duggal Abhijit, Wang Tisha S, Paolini John F, Trapnell Bruce C
Department of Cardiovascular Medicine, The Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, OH, USA.
Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, USA.
Lancet Rheumatol. 2021 Jun;3(6):e410-e418. doi: 10.1016/S2665-9913(21)00070-9. Epub 2021 Mar 17.
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.
在新型冠状病毒肺炎（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炎症反应的介质。我们旨在评估抗GM-CSF受体单克隆抗体mavrilimumab是否能改善COVID-19肺炎和全身炎症反应患者的预后。
本研究由研究者发起，为多中心、双盲、随机试验，在美国的7家医院进行。纳入标准包括住院治疗、COVID-19肺炎、低氧血症以及C反应蛋白浓度超过5mg/dL。如果患者需要机械通气则被排除。患者通过中心随机分组（1:1），并按医院地点分层，分别接受6mg/kg的mavrilimumab单次静脉输注或安慰剂。参与者以及所有临床和研究人员均对治疗分配不知情。主要终点是第14天时存活且无需补充氧气治疗的患者比例。在意向性治疗人群中分析主要结局和安全性。本试验已在ClinicalTrials.gov注册，注册号为NCT04399980、NCT04463004和NCT04492514。
2020年5月28日至9月15日期间，40例患者入组并随机分配至mavrilimumab组（n = 21）或安慰剂组（n = 19）。原计划纳入60例患者，但由于入组缓慢，该研究提前终止，以了解疾病自然史和潜在治疗效果。在第14天时，mavrilimumab组中有12例（57%）患者存活且无需补充氧气治疗，而安慰剂组中有9例（47%）患者存活且无需补充氧气治疗（优势比1.48 [95%CI 0.43 - 5.16]；p = 0.76）。没有与治疗相关的死亡病例，两组间不良事件相似。
尽管由于置信区间较宽，mavrilimumab治疗在该患者群体中的益处或危害仍有可能存在，但在第14天时存活且无需氧气治疗的患者比例并无显著差异，应完成更大规模的试验。
Kiniksa制药公司。
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