Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19.
Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19.
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DOI：
10.1056/nejmoa2102685
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发表时间：
2021-10-07
期刊：
影响因子：
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通讯作者：
BLAZE-1 Investigators
中科院分区：
文献类型：
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作者：
Dougan M;Nirula A;Azizad M;Mocherla B;Gottlieb RL;Chen P;Hebert C;Perry R;Boscia J;Heller B;Morris J;Crystal C;Igbinadolor A;Huhn G;Cardona J;Shawa I;Kumar P;Adams AC;Van Naarden J;Custer KL;Durante M;Oakley G;Schade AE;Holzer TR;Ebert PJ;Higgs RE;Kallewaard NL;Sabo J;Patel DR;Dabora MC;Klekotka P;Shen L;Skovronsky DM;BLAZE-1 Investigators
患有基础疾病的患者感染2019冠状病毒病（COVID - 19）重症的风险增加。疫苗诱导的免疫是随着时间逐渐产生的，而中和性单克隆抗体治疗可提供即时的被动免疫，并可能限制疾病进展和并发症。
在这项3期试验中，我们按1∶1的比例将一组患有轻度或中度COVID - 19且病情进展为重症风险较高的非住院患者随机分组，在实验室确诊感染严重急性呼吸综合征冠状病毒2（SARS - CoV - 2）后的3天内，分别接受单次静脉输注中和性单克隆抗体联合制剂（2800mg巴尼韦单抗和2800mg依替韦单抗，一起给药）或安慰剂。主要结局是患者的总体临床状况，定义为到第29天因COVID - 19住院或任何原因导致的死亡。
共有1035名患者接受了随机分组，并接受了巴尼韦单抗 - 依替韦单抗或安慰剂的输注。患者的平均（±标准差）年龄为53.8±16.8岁，52.0%为青春期女孩或女性。到第29天，巴尼韦单抗 - 依替韦单抗组518名患者中有11名（2.1%）因COVID - 19住院或因任何原因死亡，而安慰剂组517名患者中有36名（7.0%）（绝对风险差异为 - 4.8个百分点；95%置信区间[CI]， - 7.4至 - 2.3；相对风险差异为70%；P<0.001）。巴尼韦单抗 - 依替韦单抗组无死亡病例；安慰剂组有10例死亡，其中9例被试验研究者判定与COVID - 19相关。在第7天，接受巴尼韦单抗加依替韦单抗的患者与接受安慰剂的患者相比，对数病毒载量较基线的下降幅度更大（与安慰剂相比，从基线的变化差异为 - 1.20；95%CI， - 1.46至 - 0.94；P<0.001）。
在高风险的非住院患者中，巴尼韦单抗加依替韦单抗与安慰剂相比，导致COVID - 19相关住院和死亡的发生率更低，并加速了SARS - CoV - 2病毒载量的下降。（由礼来公司资助；BLAZE - 1 ClinicalTrials.gov编号，NCT04427501）
Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications. In this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19–related hospitalization or death from any cause by day 29. A total of 1035 patients underwent randomization and received an infusion of bamlanivimab–etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab–etesevimab group had a Covid-19–related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, −4.8 percentage points; 95% confidence interval [CI], −7.4 to −2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab–etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19–related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, −1.20; 95% CI, −1.46 to −0.94; P<0.001). Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19–related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.)