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tezepelumab治疗哮喘未得到控制的成人患者
Tezepelumab in Adults with Uncontrolled Asthma


Jonathan Corren ... 呼吸系统疾病 • 2017.09.07
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摘要


背景

在某些中度至重度哮喘患者,特别是有非嗜酸性粒细胞性炎症的患者中,病情未得到控制。tezepelumab(AMG 157/MEDI9929)是针对上皮细胞来源的细胞因子胸腺基质淋巴细胞生成素(TSLP)的特异性人单克隆抗体,本试验在使用长效β受体激动剂(LABA)和中到大剂量吸入型糖皮质激素后仍未得到控制的哮喘患者中评估了该抗体的疗效和安全性。

 

方法

在这项2期、随机、双盲、安慰剂对照试验中,我们对皮下用药的三种剂量tezepelumab和安慰剂进行了比较,治疗期为52周。主要终点为第52周时的年度哮喘加重率(每患者年的事件数)。

 

结果

tezepelumab每4周使用70 mg(小剂量,145例)、每4周使用210 mg(中剂量,145例)或者每2周使用280 mg(大剂量,146例)的患者,第52周时的年度哮喘加重率分别为0.26、0.19和0.22,安慰剂组(148例)为0.67。因此,tezepelumab各剂量组的加重率比安慰剂组分别降低61%、71%和66%(P<0.001)。无论入组时血嗜酸性粒细胞计数如何,均观察到类似的结果。所有tezepelumab组在第52周的吸入支气管扩张剂前第一秒用力呼气量(FEV1)均高于安慰剂组(小剂量组差异为0.12 L [P=0.01],中等剂量组0.11 L [P=0.02],大剂量组0.15 L [P=0.002])。共有中剂量组2例、大剂量组3例、安慰剂组1例患者由于不良事件而停止试验治疗。

 

结论

在使用长效β受体激动剂和中到大剂量吸入型糖皮质激素治疗的患者中,接受tezepelumab的患者比接受安慰剂的患者临床哮喘加重率显著降低,与基线血嗜酸性粒细胞计数无关(由MedImmune [阿斯利康集团成员]和安进公司资助;PATHWAY在ClinicalTrials.gov注册号为NCT02054130)。





作者信息

Jonathan Corren, M.D., Jane R. Parnes, M.D., Liangwei Wang, Ph.D., May Mo, M.S., Stephanie L. Roseti, A.P.N., M.S.N., Janet M. Griffiths, Ph.D., and René van der Merwe, M.B., Ch.B.
From the David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles (J.C.), and Amgen, Thousand Oaks (J.R.P., M.M.) — both in California; MedImmune, Gaithersburg, MD (L.W., S.L.R., J.M.G.); and MedImmune, Cambridge, United Kingdom (R.M.). Address reprint requests to Dr. Corren at 10780 Santa Monica Blvd., Suite 280, Los Angeles, CA 90025, or at jcorren@ucla.edu.

 

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