REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.
REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19.
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DOI：
10.1056/nejmoa2108163
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发表时间：
2021-12-02
期刊：
影响因子：
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通讯作者：
Trial Investigators
中科院分区：
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作者：
Weinreich DM;Sivapalasingam S;Norton T;Ali S;Gao H;Bhore R;Xiao J;Hooper AT;Hamilton JD;Musser BJ;Rofail D;Hussein M;Im J;Atmodjo DY;Perry C;Pan C;Mahmood A;Hosain R;Davis JD;Turner KC;Baum A;Kyratsous CA;Kim Y;Cook A;Kampman W;Roque-Guerrero L;Acloque G;Aazami H;Cannon K;Simón-Campos JA;Bocchini JA;Kowal B;DiCioccio AT;Soo Y;Geba GP;Stahl N;Lipsich L;Braunstein N;Herman G;Yancopoulos GD;Trial Investigators
在适应性试验的1-2期部分，REGEN-COV（单克隆抗体casirivimab和imdevimab的组合）减少了2019冠状病毒病（Covid-19）患者的病毒载量和就医次数。REGEN-COV在体外对当前严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变异株具有活性。在一项适应性试验的3期部分，我们随机分配患有新冠肺炎和严重疾病风险因素的门诊患者接受不同剂量的静脉注射REGEN-COV或安慰剂。患者随访至第29天。采用预先设定的分层分析评估住院或死亡的终点和症状缓解的时间。还评价了安全性。REGEN-COV 2400-mg组1355例患者中有18例发生与COVID-19相关的住院或全因死亡（1.3%），安慰剂组1341例同时接受随机化的患者中有62例（百分之四点六）（相对危险度降低[1-相对危险度]，71.3%; P<0.001）; REGEN-COV 1200 mg组736例患者中有7例发生这些结局（1.0%）和安慰剂组748例同时接受随机化的患者中的24例（3.2%）（相对风险降低，70.4%; P=0.002）。每个REGEN-COV剂量的症状缓解的中位时间比安慰剂短4天（10天vs. 14天;两种比较P<0.001）。REGEN-COV在各个亚组中有效，包括基线时SARS-CoV-2血清抗体阳性的患者。两种REGEN-COV剂量均比安慰剂更快地降低病毒载量;病毒载量从基线到第7天的最小二乘平均差异为-0.71 log 10拷贝/毫升（95%置信区间[CI]，−0.90至−0.53），2400 mg组为−0.86 log 10拷贝/毫升（95% CI，−1.00至−0.72）。安慰剂组（4.0%）严重不良事件的发生率高于1200 mg组（1.1%）和2400 mg组（1.3%）;所有组中2级或以上输注相关反应的发生率均低于0.3%。REGEN-COV降低了Covid-19相关住院或任何原因死亡的风险，并且与安慰剂相比，它更快地解决了症状并降低了SARS-CoV-2病毒载量。（由Regeneron Pharmaceuticals和其他公司资助; ClinicalTrials.gov编号，NCT 04425629。
In the phase 1–2 portion of an adaptive trial, REGEN-COV, a combination of the monoclonal antibodies casirivimab and imdevimab, reduced the viral load and number of medical visits in patients with coronavirus disease 2019 (Covid-19). REGEN-COV has activity in vitro against current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern. In the phase 3 portion of an adaptive trial, we randomly assigned outpatients with Covid-19 and risk factors for severe disease to receive various doses of intravenous REGEN-COV or placebo. Patients were followed through day 29. A prespecified hierarchical analysis was used to assess the end points of hospitalization or death and the time to resolution of symptoms. Safety was also evaluated. Covid-19–related hospitalization or death from any cause occurred in 18 of 1355 patients in the REGEN-COV 2400-mg group (1.3%) and in 62 of 1341 patients in the placebo group who underwent randomization concurrently (4.6%) (relative risk reduction [1 minus the relative risk], 71.3%; P<0.001); these outcomes occurred in 7 of 736 patients in the REGEN-COV 1200-mg group (1.0%) and in 24 of 748 patients in the placebo group who underwent randomization concurrently (3.2%) (relative risk reduction, 70.4%; P=0.002). The median time to resolution of symptoms was 4 days shorter with each REGEN-COV dose than with placebo (10 days vs. 14 days; P<0.001 for both comparisons). REGEN-COV was efficacious across various subgroups, including patients who were SARS-CoV-2 serum antibody–positive at baseline. Both REGEN-COV doses reduced viral load faster than placebo; the least-squares mean difference in viral load from baseline through day 7 was −0.71 log10 copies per milliliter (95% confidence interval [CI], −0.90 to −0.53) in the 1200-mg group and −0.86 log10 copies per milliliter (95% CI, −1.00 to −0.72) in the 2400-mg group. Serious adverse events occurred more frequently in the placebo group (4.0%) than in the 1200-mg group (1.1%) and the 2400-mg group (1.3%); infusion-related reactions of grade 2 or higher occurred in less than 0.3% of the patients in all groups. REGEN-COV reduced the risk of Covid-19–related hospitalization or death from any cause, and it resolved symptoms and reduced the SARS-CoV-2 viral load more rapidly than placebo. (Funded by Regeneron Pharmaceuticals and others; ClinicalTrials.gov number, NCT04425629.)