Tezepelumab in Adults with Uncontrolled Asthma
Tezepelumab in Adults with Uncontrolled Asthma
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DOI：
10.1056/nejmoa1704064
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发表时间：
2017-09-07
影响因子：
158.5
通讯作者：
van der Merwe, Rene
中科院分区：
文献类型：
--
作者：
Corren, Jonathan;Parnes, Jane R.;van der Merwe, Rene
研究背景在一些中重度哮喘患者中，尤其是那些非嗜酸性粒细胞性炎症患者，疾病仍然不受控制。本试验评价了tezepelumab的疗效和安全性（AMG 157/MEDI 9929），一种特异于上皮细胞衍生的细胞因子胸腺基质淋巴细胞生成素（TSLP）的人单克隆抗体，在尽管用长效β-激动剂和中高剂量的吸入性糖皮质激素治疗但哮喘仍然不受控制的患者中。我们在52周的治疗期内比较了三种剂量水平的皮下替泽匹鲁单抗与安慰剂。主要终点是哮喘急性发作的年发生率第52周时（事件/患者-年）。（低剂量; 145例患者），210 mg，每4周一次（中等剂量; 145例患者）或280 mg每2周一次（高剂量; 146例患者）导致第52周的年哮喘加重率分别为0.26、0.19和0.22，而安慰剂组（148例患者）为0.67。因此，各tezepelumab组的急性加重率分别比安慰剂组低61%、71%和66%（P
BACKGROUNDIn some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab (AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.METHODSIn this phase 2, randomized, double-blind, placebo-controlled trial, we compared subcutaneous tezepelumab at three dose levels with placebo over a 52-week treatment period. The primary end point was the annualized rate of asthma exacerbations (events per patient-year) at week 52.RESULTSThe use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P