Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.
Responses to a Neutralizing Monoclonal Antibody for Hospitalized Patients With COVID-19 According to Baseline Antibody and Antigen Levels : A Randomized Controlled Trial.
复制标题
根据基线抗体和抗原水平，对住院的Covid-19患者中和单克隆抗体的反应：一项随机对照试验。
DOI：
10.7326/m21-3507
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发表时间：
2022-03
影响因子：
39.2
通讯作者：
Neaton, J. D.
中科院分区：
文献类型：
--
作者：
Lundgren, J. D.;Gottlieb, R. L.;Sandkovsky, U.;Brown, S. M.;Baker, J., V;Ginde, A. A.;Chang, C. C.;Goodman, A. L.;Higgs, E. S.;Murray, D. D.;Murray, T. A.;Paredes, R.;Phillips, A. N.;Cao, H.;Babiker, A. G.;Davey, V. J.;Gelijns, A. C.;Kan, V. L.;Polizzotto, M. N.;Thompson, B. T.;Lane, H. C.;Neaton, J. D.
在一项随机安慰剂对照临床试验中，基于早期无效评估，bamlanivimab（一种SARS-CoV-2中和单克隆抗体）与remdesivir联合使用并没有改善住院COVID-19患者的预后。评估先验假设，即在研究开始时未检测到内源性中和抗体水平的患者中，与抗体患者相比，bamlanivimab有更大的益处，特别是在病毒水平高的情况下。随机、安慰剂对照试验。多中心试验。住院COVID-19患者无终末器官衰竭。Bamlanivimab （7000mg）或安慰剂。抗体、抗原和病毒RNA水平在基线收集的储存标本上进行集中检测。对患者进行为期90天的持续康复（定义为连续出院14天）和复合安全结果（死亡、严重不良事件、器官衰竭或严重感染）随访。在314名参与者中（163名bamlanivimab组和151名安慰剂组），持续恢复的中位时间为19天，在bamlanivimab组和安慰剂组之间没有差异，亚危险比(sHR) =0.99 (95% CI: 0.79-1.22) （sHR bbb1倾向于bamlanivimab）。入组时，50%的抗刺突中和抗体（nab）产生；50%患者的SARS-CoV-2核衣壳血浆抗原水平≥1,000 ng/L。在研究开始时没有nab和有nab的患者中，sHRs分别为1.24 （95% CI: 0.90-1.70）和0.74 (95% CI: 0.54-1.00)（相互作用的名义p=0.018）。入组时血浆抗原或鼻腔病毒RNA水平高于（低于）中位水平的患者sHR也为bbb1，无抗体和抗原或病毒RNA水平升高的患者sHR最高，分别为1.48 （95% CI: 0.99-2.23）和1.89（1.23,2.91）。复合安全性结局的危险比（< 1有利于巴兰尼韦单抗）也因入组时的血清状态而异；无nab组为0.67(0.37 ~ 1.20)，有nab组为1.79（0.92 ~ 3.48）。一项试验因无效而过早停止的亚组分析。样本量小。分析了多个亚组。bamlanivimab的有效性和安全性可能会因内源性中和抗体反应是否已经安装而有所不同。该研究的样本量有限，不能根据这些发现得出确切的结论，需要进一步的独立试验来评估在同一患者环境中其他类型的被动免疫疗法。ClinicalTrials.gov编号：NCT04501978。美国政府曲速行动和国家过敏和传染病研究所。
In a randomized, placebo controlled clinical trial, bamlanivimab, a SARS-CoV-2 neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized COVID-19 patients based on an early futility assessment. Evaluate the a priori hypothesis that there is greater benefit of bamlanivimab in patients without detectable endogenous neutralizing antibody levels at study entry compared to those with antibodies, especially if viral levels are high. Randomized, placebo-controlled trial. Multicenter trial. Hospitalized COVID-19 patients without end organ failure. Bamlanivimab (7000mg) or placebo. Antibody, antigen and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharged home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure or serious infections). Among 314 participants (163 on bamlanivimab and 151 on placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups, sub-hazard ratio (sHR) =0.99 (95% CI: 0.79–1.22) (sHR> 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike neutralizing antibodies (nAbs); 50% had SARS-CoV-2 nucleocapsid plasma antigen levels ≥ 1,000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (95% CI: 0.90–1.70) and 0.74 (95% CI: 0.54–1.00), respectively (nominal p=0.018 for interaction). The sHR was also >1 for those with plasma antigen or nasal viral RNA levels above (versus below) median level at entry and was greatest for those without antibodies and with elevated antigen or viral RNA levels: 1.48 (95% CI: 0.99–2.23), and 1.89 (1.23, 2.91), respectively. Hazard ratios for the composite safety outcome (< 1 favors bamlanivimab) also differed by serostatus at entry; 0.67 (0.37–1.20) for those without and 1.79 (0.92–3.48) for those with nAbs. Subgroup analysis of a trial prematurely stopped because of futility. Small sample size. Multiple subgroups analyzed. Efficacy and safety of bamlanivimab may differ depending on whether an endogenous neutralizing antibody response has been mounted or not. The limited sample size of the study does not allow firm conclusions based on these findings and further independent trials are required assessing other types of passive immune therapies in the same patient setting. ClinicalTrials.gov number, NCT04501978. US Government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.