Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction

Background: The 52-week, phase 3 LIBERTY ASTHMA QUEST study (NCT02414854) in patients aged above or equal to 12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilu-mab 200 mg and 300 mg every 2 weeks vs matched placebo.Objective: To assess whether dupilumab improves clinical outcomes in QUEST patients with persistent airflow obstruction (PAO) defined as post-bronchodilator forced expiratory volume in 1 second/forced vital capacity ratio less than 0.7 at baseline.Methods: End points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expira-tory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evalu-ated in patients with or without PAO at baseline in subpopulations with eosinophils >= 150 cells/mu L or fractional exhaled nitric oxide (FeNO) >= 25 ppb or eosinophils >= 300 cells/mu L and FeNO >= 25 ppb.Results: Of 1902 patients enrolled in QUEST, 1039 (55%) had PAO at baseline. Dupilumab vs placebo rapidly and significantly improved lung function in patients with PAO and elevated type 2 inflammatory biomarkers at base-line. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confi-dence interval, 1.272-2.052] and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk, 0.411; 95% confidence interval [0.327-0.516]; P < .0001) and by 75% (0.252 [0.178-0.356]; P < .0001) in patients with PAO with eosinophils >= 150 cells/mu L or FeNO >= 25 ppb and eosinophils >= 300 cells/mu L and FeNO >= 25 ppb, respectively. Similar results were observed in patient subgroups without PAO.Conclusion: In patients with uncontrolled moderate-to-severe asthma, treatment with dupilumab facilitates reversal of PAO status and improves clinical outcomes. Trial Registration: ClinicalTrials.gov identifier: NCT02414854.(c) 2022 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. This is an open access arti-cle under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

The study showed that Dupilumab is effective in improving clinical outcomes in patients with persistent airflow obstruction.