利用观察性数据模拟目标试验，比较 Casirivimab/Imdevimab 和 Bamlanivimab/Etesevimab 用于 COVID-19 非住院患者早期治疗的疗效。
Emulation of a Target Trial From Observational Data to Compare Effectiveness of Casirivimab/Imdevimab and Bamlanivimab/Etesevimab for Early Treatment of Non-Hospitalized Patients With COVID-19.
机构信息
Clinical and Infectious Diseases Research Department, National Institute for Infectious Diseases Lazzaro Spallanzani Istituiti di Ricovero e Cura a Carattere Scientifico (IRCCS), Roma, Italy.
Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London (UCL), London, United Kingdom.
出版信息
Front Immunol. 2022 Apr 20;13:868020. doi: 10.3389/fimmu.2022.868020. eCollection 2022.
OBJECTIVES
Comparative analysis between different monoclonal antibodies (mAbs) against SARS-CoV-2 are lacking. We present an emulation trial from observational data to compare effectiveness of Bamlanivimab/Etesevimab (BAM/ETE) and Casirivimab/Imdevimab (CAS/IMD) in outpatients with early mild-to-moderate COVID-19 in a real-world scenario of variants of concern (VoCs) from Alpha to Delta.
METHODS
Allocation to treatment was subject to mAbs availability, and the measured factors were not used to determine which combination to use. Patients were followed through day 30. Viral load was measured by cycle threshold (CT) on D1 (baseline) and D7.Primary outcome was time to COVID-19-related hospitalization or death from any cause over days 0-30. Weighted pooled logistic regression and marginal structural Cox model by inverse probability weights were used to compare BAM/ETE vs. CAS/IMD. ANCOVA was used to compare mean D7 CT values by intervention. Models were adjusted for calendar month, MASS score and VoCs. We evaluated effect measure modification by VoCs, vaccination, D1 CT levels and enrolment period.
RESULTS
COVID19-related hospitalization or death from any cause occurred in 15 of 237 patients in the BAM/ETE group (6.3%) and in 4 of 196 patients in the CAS/IMD group (2.0%) (relative risk reduction [1 minus the relative risk] 72%; p=0.024). Subset analysis carried no evidence that the effect of the intervention was different across stratification factors. There was no evidence in viral load reduction from baseline through day 7 across the two groups (+0.17, 95% -1.41;+1.74, p=0.83). Among patients who experienced primary outcome, none showed a negative RT-PCR test in nasopharyngeal swab (p=0.009) and 82.4% showed still high viral load (p<0.001) on D7.
CONCLUSIONS
In a pre-Omicron epidemiologic scenario, CAS/IMD reduced risk of clinical progression of COVID-19 compared to BAM/ETE. This effect was not associated with a concomitant difference in virological response.
目的
缺乏针对 SARS-CoV-2 的不同单克隆抗体（mAb）的比较分析。我们报告了一项来自观察性数据的模拟试验，以比较在 Alpha 到 Delta 变体关注（VoC）的真实世界场景中，用于门诊早期轻度至中度 COVID-19 的 Bamlanivimab/Etesevimab（BAM/ETE）和 Casirivimab/Imdevimab（CAS/IMD）的有效性。
方法
根据 mAb 的可获得性进行治疗分配，并且未使用所测量的因素来确定使用哪种组合。患者随访至第 30 天。通过 D1（基线）和 D7 的循环阈值（CT）测量病毒载量。主要结局是从第 0 天到第 30 天因任何原因引起的 COVID-19 相关住院或死亡的时间。使用逆概率权重进行加权汇总逻辑回归和边缘结构 Cox 模型来比较 BAM/ETE 与 CAS/IMD。使用干预的平均 D7 CT 值进行协方差分析。模型调整了日历月、MASS 评分和 VoC。我们通过 VoC、疫苗接种、D1 CT 水平和入组期评估了效应量修饰。
结果
在 BAM/ETE 组的 237 例患者中，有 15 例（6.3%）和 CAS/IMD 组的 196 例患者中 4 例（2.0%）发生 COVID-19 相关住院或任何原因死亡（相对风险降低[1 减去相对风险]72%；p=0.024）。亚组分析没有证据表明干预的效果在分层因素之间存在差异。两组患者在第 7 天从基线到第 7 天的病毒载量均无降低（+0.17，95%置信区间为-1.41；+1.74，p=0.83）。在发生主要结局的患者中，没有一人鼻咽拭子的 RT-PCR 检测结果为阴性（p=0.009），82.4%的患者 D7 时仍有高病毒载量（p<0.001）。
结论
在 Omicron 流行前的流行病学情况下，与 BAM/ETE 相比，CAS/IMD 降低了 COVID-19 临床进展的风险。这种效果与病毒学反应的差异无关。
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