Dupilumab reduced impact of severe exacerbations on lung function in patients with moderate-to-severe type 2 asthma
Papi, Alberto (Università degli Studi di Ferrara)
Corren, Jonathan (David Geffen School of Medicine at UCLA)
Castro, Mario (University of Kansas School of Medicine)
Domingo, Christian (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Rogers, Linda (Icahn School of Medicine at Mount Sinai)
Chapman, Kenneth R. (University of Toronto)
Jackson, Daniel J. (University of Wisconsin School of Medicine and Public Health)
Daizadeh, Nadia (Sanofi)
Pandit-Abid, Nami (Sanofi)
Gall, Rebecca (Regeneron Pharmaceuticals. Inc)
Jacob-Nara, Juby A. (Sanofi)
Rowe, Paul J. (Sanofi)
Deniz, Yamo (Regeneron Pharmaceuticals. Inc)
Ortiz, Benjamin (Regeneron Pharmaceuticals. Inc)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Severe asthma exacerbations increase the risk of accelerated lung function decline. This analysis examined the effect of dupilumab on forced expiratory volume in 1 s (FEV) in patients with moderate-to-severe asthma and elevated type 2 biomarkers from phase 3 LIBERTY ASTHMA QUEST (NCT02414854). Changes from baseline in pre- and post-bronchodilator (BD) FEV and 5-item Asthma Control Questionnaire (ACQ-5) scores were assessed in patients with elevated type 2 biomarkers at baseline (type 2-150/25: eosinophils ≥150 cells/μl and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb; type 2-300/25: eosinophils ≥300 cells/μl and/or FeNO ≥25 ppb), stratified as exacerbators (≥1 severe exacerbation during the study) or non-exacerbators. In exacerbators and non-exacerbators, dupilumab increased pre-BD FEV by Week 2 vs placebo; differences were maintained to Week 52 (type 2-150/25: LS mean difference (LSMD) vs placebo: 0. 17 L (95% CI: 0. 10-0. 24) and 0. 17 L (0. 12-0. 23); type 2-300/25: 0. 22 L (0. 13-0. 30) and 0. 21 L (0. 15-0. 28)), in exacerbators and non-exacerbators, respectively (p < . 0001). Similar trends were seen for post-BD FEV. Dupilumab vs placebo also showed significantly greater improvements in post-BD FEV 0-42 days after first severe exacerbation in type 2-150/25 (LSMD vs placebo: 0. 13 L [0. 06-0. 20]; p = . 006) and type 2-300/25 (0. 14 L [0. 06-0. 22]; p = . 001) patients. ACQ-5 improvements were greater with dupilumab vs placebo in both groups. Dupilumab treatment led to improvements in lung function independent of exacerbations and appeared to reduce the impact of exacerbations on lung function in patients who experienced a severe exacerbation during the study. This analysis assessed the effect of dupilumab on FEV in QUEST patients with moderate-to-severe asthma and elevated type 2 biomarkers. Dupilumab significantly increased FEV, regardless of number of severe exacerbations; FEV recovery was more rapid in dupilumab- vs placebo-treated patients. Dupilumab produced rapid and sustained improvement in lung function, including in patients experiencing severe exacerbations. Abbreviations: ACQ-5, 5-item Asthma Control Questionnaire; BD, bronchodilator; BL, baseline; FeNO, fractional exhaled nitric oxide; FEV, forced expiratory volume in 1 second; LS, least squares; q2w, every 2 weeks.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Dupilumab ; FEV ; Severe exacerbations ; Type 2 biomarkers
Published in:	Allergy, Vol. 78 (august 2022) , p. 233-243, ISSN 1398-9995

DOI: 10.1111/all.15456
PMID: 35899469

11 p, 2.6 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles