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 ≥12 years with uncontrolled, moderate-to-severe asthma demonstrated the efficacy and safety of dupilumab 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 <0.7 at baseline. Methods: Endpoints were annualized rate of severe exacerbations, pre-/post-bronchodilator FEV 1 over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with/without PAO at baseline in subpopulations with eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 25 ppb, or eosinophils ≥ 300 cells/µL and FeNO ≥ 25 ppb. Results: Of 1,902 patients enrolled in QUEST, 1,039 (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 baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% CI 1.272-2.052], and 1.813 [1.291-2.546]; both P < .001) and significantly reduced severe exacerbations by 69% (relative risk [RR], 95% CI 0.411 [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/µL or FeNO ≥25 ppb, and eosinophils ≥300 cells/µL 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.