Tezepelumab治疗重症未控制哮喘和常年性过敏患者的疗效
2021/08/24
摘要
背景：Tezepelumab是一种抗胸腺基质淋巴细胞生成素单克隆抗体。在PATHWAY IIb期研究（NCT02054130）中，与安慰剂相比，tezepelumab显著降低了重症未控制成人哮喘患者的年度哮喘加重率（AAER）。
目的：这项事后分析评估了tezepelumab对PATHWAY中常年性变态反应参与者的疗效。
方法：患有重症、未控制的成人哮喘患者（N=550）随机接受tezepelumab（每4周70mg或210mg，或每2周280mg）或安慰剂治疗52周。根据美国或欧盟的处方信息，对常年性空气过敏原敏感的及奥马珠单抗治疗的患者进行分组，并分析不同组别52周的AAER。在常年性变态反应亚组中评估从基线到第52周支气管扩张剂前1秒用力呼气量（FEV1）和2型（T2）生物标记物的变化。
结果：长期过敏患者（n=254）和无长期过敏患者（n=261）的AAER分别比安慰剂降低66-78%和67-71%。在52周内，无论常年过敏状态如何，tezepelumab改善了支气管扩张剂前FEV1，降低了血嗜酸性粒细胞计数和呼出一氧化氮分数。与安慰剂相比，tezepelumab在奥马珠单抗合格患者中AAER降低了61-82%（美国，n=159；欧洲，n=101），在非奥马珠单抗合格患者中AAER降低了63-70%的（美国，n=372；欧洲，n=440）。
结论：与安慰剂相比，在伴有或不伴有常年性变态反应的重症、未控制哮喘患者中，使用tezepelumab治疗可减少病情恶化，改善肺功能，减少T2生物标记物，进一步表明其在大人群的重症、未控制哮喘患者中的有效性。
Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy
Jonathan Corren, Christopher S Ambrose, Kinga Sałapa, Stephanie L Roseti, Janet M Griffiths, Jane R Parnes, Gene Colice.
Abstract
BACKGROUND:Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody. In the PATHWAY phase IIb study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma.
OBJECTIVE:This post hoc analysis assessed the efficacy of tezepelumab in PATHWAY participants with perennial allergy.
METHODS:Adults (N=550) with severe, uncontrolled asthma were randomized to receive tezepelumab (70 mg or 210 mg every 4 weeks or 280 mg every 2 weeks) or placebo, for 52 weeks. The AAER over 52 weeks was analyzed in patients grouped by sensitivity to perennial aeroallergens and by eligibility for omalizumab treatment according to the US or EU prescribing information. Change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and type 2 (T2) biomarkers were assessed in the perennial allergy subgroups.
RESULTS:Across doses, tezepelumab reduced the AAER versus placebo by 66-78% in patients with perennial allergy (n=254) and 67-71% in patients without perennial allergy (n=261). Tezepelumab improved pre-bronchodilator FEV1 and reduced blood eosinophil counts and fractional exhaled nitric oxide levels over 52 weeks, irrespective of perennial allergy status. Tezepelumab reduced the AAER versus placebo by 61-82% in omalizumab-eligible patients (US, n=159; EU, n=101) and 63-70% in omalizumab-ineligible patients (US, n=372; EU, n=440), respectively.
CONCLUSIONS:Treatment with tezepelumab reduced exacerbations, improved lung function and reduced T2 biomarkers versus placebo in patients with severe, uncontrolled asthma with or without perennial allergy, further supporting its efficacy in a broad population of patients with severe, uncontrolled asthma.
背景：Tezepelumab是一种抗胸腺基质淋巴细胞生成素单克隆抗体。在PATHWAY IIb期研究（NCT02054130）中，与安慰剂相比，tezepelumab显著降低了重症未控制成人哮喘患者的年度哮喘加重率（AAER）。
目的：这项事后分析评估了tezepelumab对PATHWAY中常年性变态反应参与者的疗效。
方法：患有重症、未控制的成人哮喘患者（N=550）随机接受tezepelumab（每4周70mg或210mg，或每2周280mg）或安慰剂治疗52周。根据美国或欧盟的处方信息，对常年性空气过敏原敏感的及奥马珠单抗治疗的患者进行分组，并分析不同组别52周的AAER。在常年性变态反应亚组中评估从基线到第52周支气管扩张剂前1秒用力呼气量（FEV1）和2型（T2）生物标记物的变化。
结果：长期过敏患者（n=254）和无长期过敏患者（n=261）的AAER分别比安慰剂降低66-78%和67-71%。在52周内，无论常年过敏状态如何，tezepelumab改善了支气管扩张剂前FEV1，降低了血嗜酸性粒细胞计数和呼出一氧化氮分数。与安慰剂相比，tezepelumab在奥马珠单抗合格患者中AAER降低了61-82%（美国，n=159；欧洲，n=101），在非奥马珠单抗合格患者中AAER降低了63-70%的（美国，n=372；欧洲，n=440）。
结论：与安慰剂相比，在伴有或不伴有常年性变态反应的重症、未控制哮喘患者中，使用tezepelumab治疗可减少病情恶化，改善肺功能，减少T2生物标记物，进一步表明其在大人群的重症、未控制哮喘患者中的有效性。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol Pract. 2021 Aug 3;S2213-2198(21)00886-2. doi: 10.1016/j.jaip.2021.07.045.)
(J Allergy Clin Immunol Pract. 2021 Aug 3;S2213-2198(21)00886-2. doi: 10.1016/j.jaip.2021.07.045.)
Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma and Perennial Allergy
Jonathan Corren, Christopher S Ambrose, Kinga Sałapa, Stephanie L Roseti, Janet M Griffiths, Jane R Parnes, Gene Colice.
Abstract
BACKGROUND:Tezepelumab is an anti-thymic stromal lymphopoietin monoclonal antibody. In the PATHWAY phase IIb study (NCT02054130), tezepelumab significantly reduced annualized asthma exacerbation rates (AAERs) versus placebo in adults with severe, uncontrolled asthma.
OBJECTIVE:This post hoc analysis assessed the efficacy of tezepelumab in PATHWAY participants with perennial allergy.
METHODS:Adults (N=550) with severe, uncontrolled asthma were randomized to receive tezepelumab (70 mg or 210 mg every 4 weeks or 280 mg every 2 weeks) or placebo, for 52 weeks. The AAER over 52 weeks was analyzed in patients grouped by sensitivity to perennial aeroallergens and by eligibility for omalizumab treatment according to the US or EU prescribing information. Change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 second (FEV1) and type 2 (T2) biomarkers were assessed in the perennial allergy subgroups.
RESULTS:Across doses, tezepelumab reduced the AAER versus placebo by 66-78% in patients with perennial allergy (n=254) and 67-71% in patients without perennial allergy (n=261). Tezepelumab improved pre-bronchodilator FEV1 and reduced blood eosinophil counts and fractional exhaled nitric oxide levels over 52 weeks, irrespective of perennial allergy status. Tezepelumab reduced the AAER versus placebo by 61-82% in omalizumab-eligible patients (US, n=159; EU, n=101) and 63-70% in omalizumab-ineligible patients (US, n=372; EU, n=440), respectively.
CONCLUSIONS:Treatment with tezepelumab reduced exacerbations, improved lung function and reduced T2 biomarkers versus placebo in patients with severe, uncontrolled asthma with or without perennial allergy, further supporting its efficacy in a broad population of patients with severe, uncontrolled asthma.
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支气管热成形术治疗哮喘:对不同哮喘内型/表型的探索性组织病理学评估
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成年患者自我相关依从性、哮喘相关生活质量与哮喘控制的相关性
