Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
Dupilumab Efficacy and Safety in Moderate-to-Severe Uncontrolled Asthma
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DOI：
10.1056/nejmoa1804092
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发表时间：
2018-06-28
影响因子：
158.5
通讯作者：
Teper, A.
中科院分区：
文献类型：
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作者：
Castro, M.;Corren, J.;Teper, A.
背景：抗白介素4受体单抗是一种完全人源性抗白介素4受体的单抗，可阻断白介素4和白介素13的信号传导。我们评估了它在未得到控制的哮喘患者中的有效性和安全性。方法我们随机将1902名12岁或12岁以上的未控制哮喘患者按2：2：1：1的比例分为两组，每两周皮下注射200或300 mg的杜匹罗单抗，或服用等量的安慰剂，疗程为52周。主要终点是在所有试验人群中使用支气管扩张剂前1秒用力呼气量(FEV1)从基线到第12周的绝对变化和严重哮喘恶化的年化比率。次要终点包括血嗜酸性粒细胞计数在每立方毫米300或以上的患者的恶化率和FEV1。结果在每2周服用200 mg杜匹单抗的患者中，严重哮喘加重的年化发生率为0.46(95%可信区间，0.39~0.53)，在配对的安慰剂组中为0.87(95%可信区间，0.72~1.05)，杜匹单抗的年发病率比安慰剂组低47.7%(P
BACKGROUNDDupilumab is a fully human anti-interleukin-4 receptor a monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. We assessed its efficacy and safety in patients with uncontrolled asthma.METHODSWe randomly assigned 1902 patients 12 years of age or older with uncontrolled asthma in a 2:2:1:1 ratio to receive add-on subcutaneous dupilumab at a dose of 200 or 300 mg every 2 weeks or matched-volume placebos for 52 weeks. The primary end points were the annualized rate of severe asthma exacerbations and the absolute change from baseline to week 12 in the forced expiratory volume in 1 second (FEV 1) before bronchodilator use in the overall trial population. Secondary end points included the exacerbation rate and FEV 1 in patients with a blood eosinophil count of 300 or more per cubic millimeter. Asthma control and dupilumab safety were also assessed.RESULTSThe annualized rate of severe asthma exacerbations was 0.46 (95% confidence interval [CI], 0.39 to 0.53) among patients assigned to 200 mg of dupilumab every 2 weeks and 0.87 (95% CI, 0.72 to 1.05) among those assigned to a matched placebo, for a 47.7% lower rate with dupilumab than with placebo (P