Abstract Rationale 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. Measurements and Main 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. Clinical trial registered with www.clinicaltrials.gov (NCT05329194).
Lugogo et al. (Fri,) studied this question.