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tezepelumab治疗成人和青少年未受控制的重症哮喘
Tezepelumab in Adults and Adolescents with Severe, Uncontrolled


Andrew Menzies-Gow ... 呼吸系统疾病 妇产科和儿科 • 2021.05.13
相关阅读
• 重度哮喘治疗的新靶点 • tezepelumab治疗哮喘未得到控制的成人患者

tezepelumab治疗未受控制重症哮喘获得3期试验证据

 

潘翠霞†,林镇烘†,关伟杰*

呼吸疾病国家重点实验室;呼吸疾病国家临床研究中心;广州呼吸健康研究院;广州医科大学附属第一医院

†第一作者;*通讯作者

 

支气管哮喘(简称哮喘)是一种异质性、慢性气道炎症疾病。哮喘的长期管理目标为控制哮喘相关症状,并降低未来哮喘急性加重的风险。重度、未控制哮喘指的是使用大剂量糖皮质激素和支气管舒张剂后,哮喘仍未能控制,频繁急性加重(≥2次/年,需口服糖皮质激素)或频繁严重急性发作(≥1次/年,需住院)1。临床上约3%~10%的患者患有重症哮喘,但是这部分患者的医疗成本负担占所有哮喘患者医疗成本的60%以上2。重症哮喘的症状、频繁发作及药物的副作用给患者带来巨大的负担。

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摘要


背景

tezepelumab是可阻断胸腺基质淋巴细胞生成素的人源性单克隆抗体,而淋巴细胞生成素是与哮喘发病机制有关的上皮细胞源性细胞因子。tezepelumab治疗未受控制的重症哮喘的疗效和安全性需要进一步评估。


方法

我们开展了一项3期、多中心、随机、双盲、安慰剂对照试验。患者(12~80岁)被随机分配接受每4周1次tezepelumab(每次210 mg)或安慰剂皮下给药,持续52周。主要终点是52周期间哮喘的年发作率。我们还在基线血嗜酸性粒细胞计数<300个/μL的患者中评估了这一终点。次要终点包括第1秒用力呼气量(FEV1)及哮喘控制问卷6(Asthma Control Questionnaire-6,ACQ-6;范围,0[无受损]~6[最严重受损])、哮喘生活质量问卷(Asthma Quality of Life Questionnaire,AQLQ;范围,1[最严重受损]~7[无受损])和哮喘症状日记(Asthma Symptom Diary,ASD;范围,0[无症状]~4[可能的最严重症状])评分。


结果

共计1,061例患者接受了随机分组(529例被分配接受tezepelumab,532例被分配接受安慰剂)。在tezepelumab组和安慰剂组中,哮喘的年发作率分别为0.93(95%置信区间[CI],0.80~1.07)和2.10(95% CI,1.84~2.39)(率比,0.44;95% CI,0.37~0.53;P<0.001)。在血嗜酸性粒细胞计数<300个/μL的患者中,tezepelumab组和安慰剂组的年发作率分别为1.02(95% CI,0.84~1.23)和1.73(95% CI,1.46~2.05)(率比,0.59;95% CI,0.46~0.75;P<0.001)。第52周时,在支气管扩张剂用药前FEV1(0.23 vs. 0.09 L;差异,0.13 L;95% CI,0.08~0.18;P<0.001),以及ACQ-6(-1.55 vs. -1.22;差异,-0.33;95% CI,-0.46~-0.20;P<0.001)、AQLQ(1.49 vs. 1.15;差异,0.34;95% CI,0.20~0.47;P<0.001)和ASD评分(-0.71 vs. -0.59;差异,-0.12;95% CI,-0.19~-0.04;P=0.002)方面,tezepelumab组的改善幅度超过安慰剂组。两组的不良事件发生率和类型不存在有意义的差异。


结论

在未受控制的重症哮喘患者中,接受tezepelumab的患者与接受安慰剂的患者相比,前者的哮喘发作较少,并且肺功能、哮喘控制情况和健康相关生活质量较好(由阿斯利康和安进资助,NAVIGATOR在ClinicalTrials.gov注册号为NCT03347279)。





作者信息

Andrew Menzies-Gow, M.D., Jonathan Corren, M.D., Arnaud Bourdin, M.D., Geoffrey Chupp, M.D., Elliot Israel, M.D., Michael E. Wechsler, M.D., Christopher E. Brightling, F.Med.Sci., Janet M. Griffiths, Ph.D., Åsa Hellqvist, M.Sc., Karin Bowen, M.Sc., Primal Kaur, M.D., Gun Almqvist, M.Sc., Sandhia Ponnarambil, M.D., and Gene Colice, M.D.
From Royal Brompton Hospital, London (A.M.-G.), Leicester National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester (C.E.B.), and Late-stage Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Cambridge (S.P.) — all in the United Kingdom; the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (J.C.), and Global Development, Amgen, Thousand Oaks (P.K.) — both in California; Physiologie et Médecine Expérimentale du Cœur et des Muscles, Université de Montpellier, Centre National de la Recherche Scientifique, INSERM, Centre Hospitalier Universitaire de Montpellier, Montpellier, France (A.B.); the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT (G. Chupp); the Division of Pulmonary and Critical Care Medicine and Allergy and Immunology, Brigham and Women’s Hospital, Harvard Medical School, Boston (E.I.); National Jewish Health, Denver (M.E.W.); Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology (J.M.G.), and Biometrics (K.B.), Late-stage Development, Respiratory and Immunology (G. Colice), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD; and Biometrics (Å.H.), Late-stage Development, Respiratory and Immunology (G.A.), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Address reprint requests to Dr. Menzies-Gow at Royal Brompton Hospital, Sydney St., London SW3 6NP, United Kingdom, or at a.menzies-gow@rbht.nhs.uk.

 

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