COVID-19 单克隆抗体的疗效比较：一个学习健康系统的随机临床试验。
The comparative effectiveness of COVID-19 monoclonal antibodies: A learning health system randomized clinical trial.
机构信息
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Wolff Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
出版信息
Contemp Clin Trials. 2022 Aug;119:106822. doi: 10.1016/j.cct.2022.106822. Epub 2022 Jun 11.
BACKGROUND
Monoclonal antibodies (mAb) that neutralize SARS-CoV-2 decrease hospitalization and death compared to placebo in patients with mild to moderate COVID-19; however, comparative effectiveness is unknown. We report the comparative effectiveness of bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab.
METHODS
A learning health system platform trial in a U.S. health system enrolled patients meeting mAb Emergency Use Authorization criteria. An electronic health record-embedded application linked local mAb inventory to patient encounters and provided random mAb allocation. Primary outcome was hospital-free days to day 28. Primary analysis was a Bayesian model adjusting for treatment location, age, sex, and time. Inferiority was defined as 99% posterior probability of an odds ratio < 1. Equivalence was defined as 95% posterior probability the odds ratio is within a given bound.
FINDINGS
Between March 10 and June 25, 2021, 1935 patients received treatment. Median hospital-free days were 28 (IQR 28, 28) for each mAb. Mortality was 0.8% (1/128), 0.8% (7/885), and 0.7% (6/922) for bamlanivimab, bamlanivimab-etesevimab, and casirivimab-imdevimab, respectively. Relative to casirivimab-imdevimab (n = 922), median adjusted odds ratios were 0.58 (95% credible interval [CI] 0.30-1.16) and 0.94 (95% CI 0.72-1.24) for bamlanivimab (n = 128) and bamlanivimab-etesevimab (n = 885), respectively. These odds ratios yielded 91% and 94% probabilities of inferiority of bamlanivimab versus bamlanivimab-etesevimab and casirivimab-imdevimab, and an 86% probability of equivalence between bamlanivimab-etesevimab and casirivimab-imdevimab.
INTERPRETATION
Among patients with mild to moderate COVID-19, bamlanivimab-etesevimab or casirivimab-imdevimab treatment resulted in 86% probability of equivalence. No treatment met prespecified criteria for statistical equivalence. Median hospital-free days to day 28 were 28 (IQR 28, 28) for each mAb.
FUNDING AND REGISTRATION
This work received no external funding. The U.S. government provided the reported mAb. This trial is registered at ClinicalTrials.gov, NCT04790786.
背景
与安慰剂相比，中和 SARS-CoV-2 的单克隆抗体（mAb）可降低轻度至中度 COVID-19 患者的住院和死亡风险；然而，其比较疗效尚不清楚。我们报告了 bamlanivimab、bamlanivimab-etesevimab 和 casirivimab-imdevimab 的比较疗效。
方法
在美国医疗系统中，一项学习健康系统平台试验招募了符合 mAb 紧急使用授权标准的患者。一个嵌入电子健康记录的应用程序将当地的 mAb 库存与患者就诊情况联系起来，并提供随机的 mAb 分配。主要结局是无住院天数至第 28 天。主要分析是一种贝叶斯模型，调整了治疗地点、年龄、性别和时间。劣势定义为后验概率 99%的优势比<1。等效性定义为后验概率在给定范围内的优势比的 95%概率。
结果
2021 年 3 月 10 日至 6 月 25 日期间，共有 1935 名患者接受了治疗。每个 mAb 的中位无住院天数为 28（IQR 28，28）。死亡率分别为 0.8%（1/128）、0.8%（7/885）和 0.7%（6/922），分别为 bamlanivimab、bamlanivimab-etesevimab 和 casirivimab-imdevimab。与 casirivimab-imdevimab（n=922）相比，bamlanivimab（n=128）和 bamlanivimab-etesevimab（n=885）的中位调整后的优势比分别为 0.58（95%可信区间[CI]0.30-1.16）和 0.94（95% CI 0.72-1.24）。这些优势比产生了 91%和 94%的 bamlanivimab 相对于 bamlanivimab-etesevimab 和 casirivimab-imdevimab 的劣势概率，以及 86%的 bamlanivimab-etesevimab 和 casirivimab-imdevimab 之间的等效概率。
解释
在轻度至中度 COVID-19 患者中，bamlanivimab-etesevimab 或 casirivimab-imdevimab 治疗的等效概率为 86%。没有一种治疗方法符合预设的统计学等效标准。无住院天数至第 28 天的中位数分别为 28（IQR 28，28）。
资金和注册
这项工作没有得到外部资金的支持。报告的 mAb 由美国政府提供。该试验在 ClinicalTrials.gov 注册，NCT04790786。
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