Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma
Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma
复制标题
DOI：
10.1056/nejmoa2034975
复制
发表时间：
2021-05-13
影响因子：
158.5
通讯作者：
Colice, Gene
中科院分区：
文献类型：
--
作者：
Menzies-Gow, Andrew;Corren, Jonathan;Colice, Gene
Tezepelumab治疗严重、失控的哮喘Tezepelumab是一种单抗，可以阻断胸腺基质淋巴生成素，后者是一种上皮细胞衍生的细胞因子，与哮喘的发病有关。这项随机、安慰剂对照的临床试验显示，在接受替赛乐单抗治疗的严重、未控制哮喘的患者中，哮喘恶化的年化比率降低。替赛乐单抗是一种人类单抗，可以阻断胸腺基质淋巴生成素，这是一种与哮喘发病有关的上皮细胞衍生细胞因子。我们进行了一项3阶段的多中心、随机、双盲、安慰剂对照试验。患者(12-80岁)被随机分配接受替赛乐单抗(210 Mg)或安慰剂皮下注射，每4周一次，共52周。主要终点是52周期间哮喘恶化的年化比率。这一终点也在基线血嗜酸性粒细胞计数低于每微升300个的患者中进行了评估。次要终点包括1秒用力呼气量(FEV1)和哮喘控制问卷-6(ACQ-6；范围为0[无损害]至6[最大损害])、哮喘生活质量问卷(AQLQ；范围为1[最大损害]至7[无损害])和哮喘症状日记(ASD；范围为0[无症状]至4[最严重症状])的评分。替赛乐单抗和安慰剂组的年哮喘加重率分别为0.93(95%可信区间，0.80~1.07)和2.10(95%可信区间，1.84~2.39)(比率比，0.44；95%可信区间，0.37~0.53；P
Tezepelumab in Severe, Uncontrolled AsthmaTezepelumab is a monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. This randomized, placebo-controlled clinical trial showed a reduction in the annualized rate of asthma exacerbations among patients with severe, uncontrolled asthma treated with tezepelumab.BackgroundTezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial-cell-derived cytokine implicated in the pathogenesis of asthma. The efficacy and safety of tezepelumab in patients with severe, uncontrolled asthma require further assessment.MethodsWe conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients (12 to 80 years of age) were randomly assigned to receive tezepelumab (210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The primary end point was the annualized rate of asthma exacerbations over a period of 52 weeks. This end point was also assessed in patients with baseline blood eosinophil counts of less than 300 cells per microliter. Secondary end points included the forced expiratory volume in 1 second (FEV1) and scores on the Asthma Control Questionnaire-6 (ACQ-6; range, 0 [no impairment] to 6 [maximum impairment]), Asthma Quality of Life Questionnaire (AQLQ; range, 1 [maximum impairment] to 7 [no impairment]), and Asthma Symptom Diary (ASD; range, 0 [no symptoms] to 4 [worst possible symptoms]).ResultsOverall, 1061 patients underwent randomization (529 were assigned to receive tezepelumab and 532 to receive placebo). The annualized rate of asthma exacerbations was 0.93 (95% confidence interval [CI], 0.80 to 1.07) with tezepelumab and 2.10 (95% CI, 1.84 to 2.39) with placebo (rate ratio, 0.44; 95% CI, 0.37 to 0.53; P