Tezepelumab in real-world US patients with severe asthma across phenotypes and underrepresented populations: the phase 4 PASSAGE study.

Abstract

Clinical trials of severe asthma therapies often exclude or underrepresent key patient populations. To evaluate the effectiveness and safety of tezepelumab in a diverse, real-world US population with severe, uncontrolled asthma (SUA). 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 or <300 cells/µL, with or without allergy) and underrepresented populations (Black/African American patients, adolescents, those with SUA with comorbid mild-to-moderate chronic obstructive pulmonary disease, people with a significant smoking history [≥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. Among 286 participants, AAER decreased by 70% (95% CI, 63%-75%) from 2.88 (baseline period) to 0.87 (treatment period) and by 54% to 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% to 91% of participants across phenotypes and underrepresented populations at week 52. No new safety signals were identified. The PASSAGE study of a diverse, real-world US population with SUA treated with tezepelumab demonstrated substantial reductions in asthma exacerbations across phenotypes and underrepresented populations as well as clinically meaningful improvements in lung function, asthma control, and health-related quality of life. www.clinicaltrials.gov (NCT05329194).