tezepelumab在美国不同严重哮喘患者群体中的有效性和安全性：PASSAGE研究的初步结果

Effectiveness and Safety of Tezepelumab in a Diverse Population of US Patients with Severe Asthma: Initial Results of the PASSAGE Study.

作者信息

Lugogo Njira L, Akuthota Praveen, Sumino Kaharu, Mathur Sameer K, Burnette Autumn F, Lindsley Andrew W, Llanos Jean-Pierre, Marchese Claudio, Ambrose Christopher S, Emmanuel Benjamin

机构信息

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA.

Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla, CA, USA.

出版信息

Adv Ther. 2025 Jul;42(7):3334-3353. doi: 10.1007/s12325-025-03231-6. Epub 2025 May 19.

DOI:10.1007/s12325-025-03231-6

PMID:40388086

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12182456/

Abstract

INTRODUCTION

Clinical trials for severe uncontrolled asthma (SUA) often underrepresent or exclude key patient populations. The phase 4 PASSAGE study assesses the effectiveness and safety of tezepelumab in a diverse, real-world US population of patients with SUA.

METHODS

PASSAGE is an ongoing, multicenter, single-arm, open-label study of patients (≥ 12 years) with SUA. The study enrolled participants across asthma phenotypes, based on blood eosinophil counts (BECs) (≥/< 300 cells/µL) and perennial aeroallergen sensitization, and underrepresented subgroups (Black/African Americans, adolescents, participants with comorbid mild to moderate chronic obstructive pulmonary disease (COPD) and smokers [≥ 10 pack-years]). Participants receive tezepelumab 210 mg subcutaneously every 4 weeks for 52 weeks. This interim analysis assessed annualized asthma exacerbation rates (AAERs) in the 12-month baseline period (before starting tezepelumab) and the treatment period, and changes from baseline to week 24 in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV), Asthma Control Questionnaire-6 (ACQ-6) score and health-related quality of life (HRQoL) outcomes.

RESULTS

Of 208 participants in this analysis, 41% had BEC ≥ 300 cells/µL, 56% had confirmed allergy, 17% were Black/African American, 5% were adolescents, 13% had comorbid COPD, and 23% were smokers. The AAER decreased by 76% (95% CI (confidence interval): 69, 81) from baseline to the treatment period; comparable reductions were observed across asthma phenotypes and underrepresented subgroups. The least squares mean change from baseline to week 24 in pre-BD FEV was 0.11 L (95% CI: 0.06, 0.17) overall and 0.19 L (95% CI: 0.12, 0.25) among participants with baseline pre-BD FEV ≤ 80% predicted. Clinically meaningful improvements from baseline to week 24 were observed for ACQ-6 score and HRQoL outcomes. No new safety signals were identified.

CONCLUSION

The PASSAGE study of US patients with SUA treated with tezepelumab demonstrates substantial reductions in AAERs across asthma phenotypes and underrepresented subgroups, with clinically meaningful improvements in lung function, asthma control and HRQoL.

TRIAL REGISTRATION

ClinicalTrials.gov identifier, NCT05329194.

摘要

引言

重度未控制哮喘（SUA）的临床试验往往不能充分代表或排除关键患者群体。4期PASSAGE研究评估了tezepelumab在美国不同的真实世界SUA患者群体中的有效性和安全性。

方法

PASSAGE是一项正在进行的、多中心、单臂、开放标签的研究，纳入了年龄≥12岁的SUA患者。该研究根据血液嗜酸性粒细胞计数（BECs）（≥/<300个细胞/μL）和常年性气传变应原致敏情况，纳入了各种哮喘表型的参与者，以及代表性不足的亚组（黑人/非裔美国人、青少年、合并轻度至中度慢性阻塞性肺疾病（COPD）的参与者和吸烟者[≥10包年]）。参与者每4周皮下注射一次210mg的tezepelumab，持续52周。这项中期分析评估了12个月基线期（开始使用tezepelumab之前）和治疗期的年化哮喘加重率（AAERs），以及支气管扩张剂前（BD）1秒用力呼气量（FEV）、哮喘控制问卷-6（ACQ-6）评分和健康相关生活质量（HRQoL）结果从基线到第24周的变化。

结果

在本次分析的208名参与者中，41%的人BEC≥300个细胞/μL，56%的人确诊过敏，17%为黑人/非裔美国人，5%为青少年，13%合并COPD，23%为吸烟者。从基线期到治疗期，AAER下降了76%（95%置信区间（CI）：69，81）；在各种哮喘表型和代表性不足的亚组中观察到了类似程度的降低。支气管扩张剂前FEV从基线到第24周的最小二乘均值变化总体为0.11L（95%CI：0.06，0.17），基线支气管扩张剂前FEV≤预测值80%的参与者中为0.19L（95%CI：0.12，0.25）。从基线到第24周，ACQ-6评分和HRQoL结果有临床意义的改善。未发现新的安全信号。