Tezepelumab 在美国真实世界不同表型及代表性不足人群中的严重哮喘患者中的应用：Ⅳ 期 PASSAGE 研究
2026/06/01
摘要
背景：针对严重哮喘疗法的临床试验常常排除或未能充分代表关键患者人群。
目的：在多样化且符合真实世界情况的美国严重未控制哮喘（SUA）患者人群中，评估 tezepelumab 的有效性和安全性。
方法：PASSAGE是一项Ⅳ期、多中心、单臂、开放标签、为期12个月的研究，入组了SUA患者（年龄≥12岁），涵盖不同表型（血嗜酸性粒细胞计数≥300/<300个细胞/µL，伴或不伴过敏）以及代表性不足的人群（黑/非裔美国人患者、青少年、合并轻度至中度慢性阻塞性肺疾病的SUA患者、吸烟者[吸烟量≥10包年]）。主要结局指标是启动tezepelumab治疗前12个月（基线期）和治疗后12个月（治疗期）的年化哮喘急性发作率（AAER）。
结果 ：在286名参与者中，AAER从基线期的2.88降至治疗期的0.87，降幅为70%（95% CI:63, 75）；在不同表型和代表性不足的人群中，降幅为54–77%。至第52周时，总体人群中吸入支气管扩张剂前FEV₁的最小二乘均值较基线增加 0.122L（95%CI:0.07,0.17）；在基线时吸入支气管扩张剂前FEV₁占预计值百分比≤80%的参与者中，增加0.212L（95%CI: 0.15,0.28）。至第52周时，在哮喘控制问卷-6、哮喘损害与风险问卷以及圣乔治呼吸问卷评分方面，不同表型和代表性不足的人群中有51–91%的参与者取得了具有临床意义的改善。未发现新的安全性信号。
结论：针对多样化、真实世界美国SUA人群使用tezepelumab的PASSAGE研究表明，在不同表型和代表性不足的人群中，哮喘急性发作率显著降低，并且在肺功能、哮喘控制以及健康相关生活质量方面取得了具有临床意义的改善。
Tezepelumab in Real-World U.S. Patients with Severe Asthma Across Phenotypes and Underrepresented Populations: The Phase 4 PASSAGE Study
Lugogo NL, Akuthota P, Sumino K, et.al
Abstract
BACKGROUND:
Clinical trials of severe asthma therapies often exclude or underrepresent key patient populations.
OBJECTIVES:
To evaluate the effectiveness and safety of tezepelumab in a diverse, real-world U.S. population with severe, uncontrolled asthma (SUA).
METHODS:
PASSAGE was a phase 4, multicenter, single-arm, open-label, 12-month study enrolling patients with SUA (≥12 years old), including different phenotypes (blood eosinophil count ≥/<300 cells/µL, with/without allergy) and underrepresented populations (Black/African American patients, adolescents, SUA with comorbid mild-to-moderate COPD, smokers [≥10 pack-years]). The primary outcome was the annualized asthma exacerbation rate (AAER) in the 12 months before (baseline period) and after (treatment period) tezepelumab initiation.
RESULTS:
Among 286 participants, AAER decreased 70% (95% CI: 63, 75) from 2.88 (baseline period) to 0.87 (treatment period) and by 54-77% across phenotypes and underrepresented populations. At week 52, least-squares mean pre-bronchodilator FEV1 increased from baseline by 0.122 L (95% CI: 0.07, 0.17) overall and by 0.212 L (95% CI: 0.15, 0.28) among participants with percent predicted pre-bronchodilator FEV1 ≤ 80% at baseline. Clinically meaningful improvements in Asthma Control Questionnaire-6, Asthma Impairment and Risk Questionnaire, and St George's Respiratory Questionnaire scores were observed in 51-91% of participants across phenotypes and underrepresented populations at week 52. No new safety signals were identified.
CONCLUSIONS:
The PASSAGE study of a diverse, real-world U.S. population with SUA treated with tezepelumab demonstrated substantial reductions in asthma exacerbations across phenotypes and underrepresented populations, and clinically meaningful improvements in lung function, asthma control, and health-related quality of life.
背景：针对严重哮喘疗法的临床试验常常排除或未能充分代表关键患者人群。
目的：在多样化且符合真实世界情况的美国严重未控制哮喘（SUA）患者人群中，评估 tezepelumab 的有效性和安全性。
方法：PASSAGE是一项Ⅳ期、多中心、单臂、开放标签、为期12个月的研究，入组了SUA患者（年龄≥12岁），涵盖不同表型（血嗜酸性粒细胞计数≥300/<300个细胞/µL，伴或不伴过敏）以及代表性不足的人群（黑/非裔美国人患者、青少年、合并轻度至中度慢性阻塞性肺疾病的SUA患者、吸烟者[吸烟量≥10包年]）。主要结局指标是启动tezepelumab治疗前12个月（基线期）和治疗后12个月（治疗期）的年化哮喘急性发作率（AAER）。
结果 ：在286名参与者中，AAER从基线期的2.88降至治疗期的0.87，降幅为70%（95% CI:63, 75）；在不同表型和代表性不足的人群中，降幅为54–77%。至第52周时，总体人群中吸入支气管扩张剂前FEV₁的最小二乘均值较基线增加 0.122L（95%CI:0.07,0.17）；在基线时吸入支气管扩张剂前FEV₁占预计值百分比≤80%的参与者中，增加0.212L（95%CI: 0.15,0.28）。至第52周时，在哮喘控制问卷-6、哮喘损害与风险问卷以及圣乔治呼吸问卷评分方面，不同表型和代表性不足的人群中有51–91%的参与者取得了具有临床意义的改善。未发现新的安全性信号。
结论：针对多样化、真实世界美国SUA人群使用tezepelumab的PASSAGE研究表明，在不同表型和代表性不足的人群中，哮喘急性发作率显著降低，并且在肺功能、哮喘控制以及健康相关生活质量方面取得了具有临床意义的改善。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Am J Respir Crit Care Med. 2026 May 18:aamag225.DOI: 10.1093/ajrccm/aamag225）
（Am J Respir Crit Care Med. 2026 May 18:aamag225.DOI: 10.1093/ajrccm/aamag225）
Tezepelumab in Real-World U.S. Patients with Severe Asthma Across Phenotypes and Underrepresented Populations: The Phase 4 PASSAGE Study
Lugogo NL, Akuthota P, Sumino K, et.al
Abstract
BACKGROUND:
Clinical trials of severe asthma therapies often exclude or underrepresent key patient populations.
OBJECTIVES:
To evaluate the effectiveness and safety of tezepelumab in a diverse, real-world U.S. population with severe, uncontrolled asthma (SUA).
METHODS:
PASSAGE was a phase 4, multicenter, single-arm, open-label, 12-month study enrolling patients with SUA (≥12 years old), including different phenotypes (blood eosinophil count ≥/<300 cells/µL, with/without allergy) and underrepresented populations (Black/African American patients, adolescents, SUA with comorbid mild-to-moderate COPD, smokers [≥10 pack-years]). The primary outcome was the annualized asthma exacerbation rate (AAER) in the 12 months before (baseline period) and after (treatment period) tezepelumab initiation.
RESULTS:
Among 286 participants, AAER decreased 70% (95% CI: 63, 75) from 2.88 (baseline period) to 0.87 (treatment period) and by 54-77% across phenotypes and underrepresented populations. At week 52, least-squares mean pre-bronchodilator FEV1 increased from baseline by 0.122 L (95% CI: 0.07, 0.17) overall and by 0.212 L (95% CI: 0.15, 0.28) among participants with percent predicted pre-bronchodilator FEV1 ≤ 80% at baseline. Clinically meaningful improvements in Asthma Control Questionnaire-6, Asthma Impairment and Risk Questionnaire, and St George's Respiratory Questionnaire scores were observed in 51-91% of participants across phenotypes and underrepresented populations at week 52. No new safety signals were identified.
CONCLUSIONS:
The PASSAGE study of a diverse, real-world U.S. population with SUA treated with tezepelumab demonstrated substantial reductions in asthma exacerbations across phenotypes and underrepresented populations, and clinically meaningful improvements in lung function, asthma control, and health-related quality of life.
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Tezepelumab治疗重度哮喘的一年期临床缓解：TERESA单臂前瞻性研究
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人工智能整合多组学方法在重度哮喘中的当前认识与未来方向
