Objective 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. Design 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. Participants Hospitalised COVID-19 participants (N=520) with SpO2 ≤94% on room air or requiring supplemental oxygen but not invasive mechanical ventilation. Interventions Lenzilumab (1800 mg; three divided doses, q8h, within 24 hours) or placebo infusion alongside corticosteroid and remdesivir treatments. Main outcome measures The primary endpoint was the time-to-event analysis difference in SWOV through day 28 between lenzilumab and placebo treatments, stratified by baseline CRP. Results 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. Conclusion Hospitalised hypoxemic patients with COVID-19 with baseline CRP <150 mg/L derived the greatest clinical benefit from treatment with lenzilumab. Trial registration number [NCT04351152; ClinicalTrials.gov][1] All data relevant to the study are included in the article or uploaded as supplementary information. Not Applicable. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04351152&atom=%2Fthoraxjnl%2F78%2F6%2F606.atom

中文翻译：

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C 反应蛋白利用是早期 COVID-19 治疗的生物标志物，可提高 lenzilumab 疗效：随机 3 期“LIVE-AIR”试验的结果


目的 COVID-19 严重程度与粒细胞巨噬细胞集落刺激因子 (GM-CSF) 和 C 反应蛋白 (CRP) 水平相关。在第三阶段的 LIVE-AIR 试验中，lenzilumab（一种抗 GM-CSF 单克隆抗体）提高了 COVID-19 患者无通气生存 (SWOV) 的可能性，对基线 CRP 中位数低于 79 mg/的参与者效果最大L。在此，评估了基线 CRP 指导 lenzilumab 治疗的效用。设计 对随机、盲法、对照、LIVE-AIR 试验进行亚分析，其中在第 0 天给予 lenzilumab 或安慰剂，并对参与者进行随访至第 28 天。 参与者 住院的 COVID-19 参与者 (N=520)，其 SpO2 ≤ 94%室内空气或需要补充氧气但不需要有创机械通气。干预 Lenzilumab（1800 mg；分三剂量，每 8 小时一次，24 小时内）或安慰剂输注，同时进行皮质类固醇和瑞德西韦治疗。主要结局指标 主要终点是 lenzilumab 和安慰剂治疗之间截至第 28 天 SWOV 的时间到事件分析差异，按基线 CRP 分层。结果 152 名（90%；95% CI 85 至 94）lenzilumab 和 144 名（79%；72 至 84）名安慰剂治疗参与者（基线 CRP <150 mg/L）实现了 SWOV（HR：2.54；95% CI 1.46 至 94）。 4.41；p=0.0009），但 CRP ≥150 mg/L 则不然（HR：1.04；95% CI 0.51 至 2.14；p=0.9058）。观察到 CRP 和 lenzilumab 治疗之间存在统计学上显着的相互作用 (p=0.044)。在两个 CRP 层中，lenzilumab 的 ≥3 级不良事件与安慰剂相当。没有因治疗引起的严重不良事件归因于lenzilumab。 结论 基线 CRP <150 mg/L 的住院低氧血症 COVID-19 患者从 lenzilumab 治疗中获得最大的临床获益。试用注册号[NCT04351152； ClinicalTrials.gov][1] 与研究相关的所有数据均包含在文章中或作为补充信息上传。不适用。 [1]：/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04351152&atom=%2Fthoraxjnl%2F78%2F6%2F606。原子