C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.
C reactive protein utilisation, a biomarker for early COVID-19 treatment, improves lenzilumab efficacy: results from the randomised phase 3 'LIVE-AIR' trial.
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新冠肺炎的严重程度与粒细胞-巨噬细胞集落刺激因子和C反应蛋白水平相关。在第三阶段的现场试验中，抗粒细胞巨噬细胞集落刺激因子的单抗Lenzilumab可提高新冠肺炎患者在不使用呼吸机的情况下存活的可能性，其中基线C反应蛋白中值低于79 mg/L的受试者效果最好。这是一项随机、盲目、对照、现场试验的子分析，在该试验中，在第0天给予lenzilumab或安慰剂，并对参与者进行跟踪，直到第28天。住院的新冠肺炎参与者(N=520)，SpO2≤94%在室内空气中或需要补充氧气但不需要有创机械通气。Lenzilumab(1800毫克；分三次剂量，每8小时一次，24小时内)或安慰剂输注，同时给予皮质类固醇和雷米西韦治疗。主要终点是Lenzilumab和安慰剂治疗之间的SWOV在第28天的事件发生时间分析差异，按基线CRP分层。CRP150 mg/L(HR：2.54；95%CI 1.46~4.41；p=0.0009)的Lenzilumab组和144例(79%；72~84)安慰剂治疗组的受试者获得了SWOV，但CRP150 mg/≥组(HR：1.04；95%CI 0.51~2.14；p=0.9058)未达到SWOV。观察到C反应蛋白和伦齐鲁单抗治疗之间有统计学意义的交互作用(p=0.044)。在两组≥中，使用来昔洛单抗的CRP3级不良事件与安慰剂相当。没有治疗紧急严重不良事件归因于伦齐卢单抗。基线C反应蛋白水平为150毫克/L的新冠肺炎低氧血症住院患者从伦齐卢单抗治疗中获得了最大的临床益处。NCT04351152；ClinicalTrials.gov
COVID-19 severity is correlated with granulocyte macrophage colony-stimulating factor (GM-CSF) and C reactive protein (CRP) levels. In the phase three LIVE-AIR trial, lenzilumab an anti-GM-CSF monoclonal antibody, improved the likelihood of survival without ventilation (SWOV) in COVID-19, with the greatest effect in participants having baseline CRP below a median of 79 mg/L. Herein, the utility of baseline CRP to guide lenzilumab treatment was assessed. A subanalysis of the randomised, blinded, controlled, LIVE-AIR trial in which lenzilumab or placebo was administered on day 0 and participants were followed through Day 28. Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. SWOV was achieved in 152 (90%; 95% CI 85 to 94) lenzilumab and 144 (79%; 72 to 84) placebo-treated participants with baseline CRP <150 mg/L (HR: 2.54; 95% CI 1.46 to 4.41; p=0.0009) but not with CRP ≥150 mg/L (HR: 1.04; 95% CI 0.51 to 2.14; p=0.9058). A statistically significant interaction between CRP and lenzilumab treatment was observed (p=0.044). Grade ≥3 adverse events with lenzilumab were comparable to placebo in both CRP strata. No treatment-emergent serious adverse events were attributed to lenzilumab. Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. NCT04351152; ClinicalTrials.gov
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影响因子：
7.4
作者：
Blot M;Bour JB;Quenot JP;Bourredjem A;Nguyen M;Guy J;Monier S;Georges M;Large A;Dargent A;Guilhem A;Mouries-Martin S;Barben J;Bouhemad B;Charles PE;Chavanet P;Binquet C;Piroth L;LYMPHONIE study group
通讯作者：
LYMPHONIE study group
影响因子：
2.9
作者：
Hodges G;Pallisgaard J;Schjerning Olsen AM;McGettigan P;Andersen M;Krogager M;Kragholm K;Køber L;Gislason GH;Torp-Pedersen C;Bang CN
通讯作者：
Bang CN
影响因子：
8
作者：
Plaçais L;Richier Q;Noël N;Lacombe K;Mariette X;Hermine O
通讯作者：
Hermine O
DOI：
10.1016/s2213-2600(21)00494-x
发表时间：
2022-03
期刊：
The Lancet. Respiratory medicine
影响因子：
--
作者：
Temesgen Z;Burger CD;Baker J;Polk C;Libertin CR;Kelley CF;Marconi VC;Orenstein R;Catterson VM;Aronstein WS;Durrant C;Chappell D;Ahmed O;Chappell G;Badley AD;LIVE-AIR Study Group
通讯作者：
LIVE-AIR Study Group
DOI：
10.1016/j.cmi.2020.09.021
发表时间：
2021-03
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Martínez-Sanz J;Muriel A;Ron R;Herrera S;Pérez-Molina JA;Moreno S;Serrano-Villar S
通讯作者：
Serrano-Villar S