美国礼来公司Daniel M. Skovronsky团队比较了bamlanivimab单药或联合etesevimab治疗轻中度COVID-19患者对病毒载量的影响。2021年1月21日，该研究发表在《美国医学会杂志》上。

COVID-19继续在全球迅速传播。中和抗体是一种潜在的治疗COVID-19的方法。

为了探讨bamlanivimab单药，以及联合etesevimab治疗轻中度COVID-19患者对SARS-CoV-2病毒载量的影响，研究组在美国的49个中心进行了一项临床2/3期的随机试验，共招募了613名门诊患者，这些患者的SARS-CoV-2感染检测呈阳性，有1种或多种轻中度症状。将患者随机分组，其中101例接受单次输注bamlanivimab 700 mg，107例接受单次输注bamlanivimab 2800 mg，101例接受单次输注bamlanivimab 7000 mg，112例接受输注2800 mg bamlanivimab联合2800 mg etesevimab，156例接受输注安慰剂。主要终点是第11天SARS-CoV-2对数病毒载量的变化。

577名随机接受输液的患者平均年龄为44.7岁，其中54.6%为女性，共有533名（92.4%）完成了疗效评估期（第29天）。与基线检查时相比，第11天的对数病毒载量变化为：700 mg组降低3.72，2800 mg组降低4.08，7000 mg组降低3.49，联合治疗组降低4.37，安慰剂组降低3.80。与安慰剂组相比，第11天的对数病毒载量变化差异为：700 mg组增加0.09，2800 mg组降低0.27，7000 mg组增加0.31，联合治疗组降低0.57，仅联合治疗组有显著差异。

在84个次要终点中，有10个在各治疗组与安慰剂组之间具有统计学差异。与COVID-19相关的住院或ED就诊的患者比例，安慰剂组为5.8%（9个事件），700 mg组为1.0%（1个事件），2800 mg组为1.9%（2个事件），7000 mg组为2.0%（2个事件），联合治疗组为0.9%（1个事件）。共有9例患者（bamlanivimab组有6例，联合治疗组有2例，安慰剂组有1例）出现即时超敏反应。研究治疗期间未发生死亡。

研究结果表明，对于轻中度COVID-19疾病的非住院患者，与安慰剂相比，使用bamlanivimab联合etesevimab治疗，在第11天时可显著降低SARS-CoV-2病毒载量。

附：英文原文

Title: Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19: A Randomized Clinical Trial

Author: Robert L. Gottlieb, Ajay Nirula, Peter Chen, Joseph Boscia, Barry Heller, Jason Morris, Gregory Huhn, Jose Cardona, Bharat Mocherla, Valentina Stosor, Imad Shawa, Princy Kumar, Andrew C. Adams, Jacob Van Naarden, Kenneth L. Custer, Michael Durante, Gerard Oakley, Andrew E. Schade, Timothy R. Holzer, Philip J. Ebert, Richard E. Higgs, Nicole L. Kallewaard, Janelle Sabo, Dipak R. Patel, Paul Klekotka, Lei Shen, Daniel M. Skovronsky

Issue&Volume: 2021-01-21

Abstract:

Importance  Coronavirus disease 2019 (COVID-19) continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19.

Objective  To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19.

Design, Setting, and Participants  The BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N=613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020.

Interventions  Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n=101], 2800 mg [n=107], or 7000 mg [n=101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n=112]), or placebo (n=156).

Main Outcomes and Measures  The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19–related hospitalization, an emergency department [ED] visit, or death at day 29).

Results  Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was –3.72 for 700 mg, –4.08 for 2800 mg, –3.49 for 7000 mg, –4.37 for combination treatment, and –3.80 for placebo. Compared with placebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, –0.35 to 0.52; P=.69) for 700 mg, –0.27 (95% CI, –0.71 to 0.16; P=.21) for 2800 mg, 0.31 (95% CI, –0.13 to 0.76; P=.16) for 7000 mg, and –0.57 (95% CI, –1.00 to –0.14; P=.01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group were statistically significant for 10 of 84 end points. The proportion of patients with COVID-19–related hospitalizations or ED visits was 5.8% (9 events) for placebo, 1.0% (1 event) for 700 mg, 1.9% (2 events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment.

Conclusions and Relevance  Among nonhospitalized patients with mild to moderate COVID-19 illness, treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point.

DOI: 10.1001/jama.2021.0202

Source: https://jamanetwork.com/journals/jama/fullarticle/2775647