TY - JOUR
T1 - Efficacy of dupilumab in patients with moderate-to-severe asthma and persistent airflow obstruction
AU - Hanania, N.A.
AU - Castro, M.
AU - Bateman, E.
AU - Pavord, I.D.
AU - Papi, A.
AU - FitzGerald, J.M.
AU - Maspero, J.F.
AU - Katelaris, Constance H.
AU - Singh, D.
AU - Daizadeh, N.
AU - Altincatal, A.
AU - Pandit-Abid, N.
AU - Soler, X.
AU - Siddiqui, S.
AU - Laws, E.
AU - Jacob-Nara, J.A.
AU - Rowe, P.J.
AU - Lederer, D.J.
AU - Hardin, M.
AU - Deniz, Y.
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - 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 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 less than 0.7 at baseline. Methods: End points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or 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 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 baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence 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/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. Trial Registration: ClinicalTrials.gov identifier: NCT02414854.
AB - 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 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 less than 0.7 at baseline. Methods: End points were annualized rate of severe exacerbations, pre and post-bronchodilator forced expiratory volume in 1 second over time, proportion achieving reversal of PAO, and quality of life. Efficacy was evaluated in patients with or 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 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 baseline. Dupilumab improved probability of reversing airflow obstruction (hazard ratio vs placebo 1.616 [95% confidence 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/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. Trial Registration: ClinicalTrials.gov identifier: NCT02414854.
UR - https://hdl.handle.net/1959.7/uws:73750
UR - http://www.scopus.com/inward/record.url?scp=85143525382&partnerID=8YFLogxK
U2 - 10.1016/j.anai.2022.10.018
DO - 10.1016/j.anai.2022.10.018
M3 - Article
SN - 1081-1206
VL - 130
SP - 206-214.e2
JO - Annals of Allergy , Asthma and Immunology
JF - Annals of Allergy , Asthma and Immunology
IS - 2
ER -
