Transient early blood eosinophil increases do not affect dupilumab’s long-term efficacy in patients with moderate-to-severe asthma - 23/12/25

Doi : 10.1016/j.jaci.2025.07.037

Ian D. Pavord, MD ^a,^⁎ , Njira L. Lugogo, MD ^b, Mario Castro, MD ^c, Alberto Papi, MD ^d, Arnaud Bourdin, MD ^e, Michael E. Wechsler, MD ^f, Andréanne Côté, MD ^g, Kenneth R. Chapman, MD ^h, Changming Xia, PhD ⁱ, Mena Soliman, MD ⁱ, Nami Pandit-Abid, PharmD ^j, Juby A. Jacob-Nara, MD, DHSc ^j, Harry Sacks, MD ⁱ
^a NIHR Oxford Respiratory Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
^b University of Michigan, Ann Arbor, Mich
^c Division of Pulmonary, Critical Care and Sleep Medicine, University of Kansas School of Medicine, Kansas City, Kan
^d Respiratory Medicine Unit, University of Ferrara, S. Anna University Hospital, Ferrara, Italy
^e Department of Respiratory Diseases, PhyMedExp INSERM CNRS, University of Montpellier, Montpellier, France
^f Division of Pulmonary, Critical Care and Sleep Medicine, National Jewish Health, Denver, Colo
^g Quebec Heart and Lung Institute, Laval University, Quebec, Quebec, Canada
^h University of Toronto, Toronto, Ontario, Canada
ⁱ Regeneron Pharmaceuticals Inc, Tarrytown, NY
^j Sanofi, Bridgewater, NJ

^∗Corresponding author: Ian D. Pavord, MD, Respiratory Medicine Unit and Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Room 7400, Level 7EF, John Radcliffe Hospital, Oxford OX3 9DU.NIHR Oxford Respiratory Biomedical Research CentreNuffield Department of MedicineUniversity of OxfordOxford

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 23 December 2025

Graphical abstract

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Abstract

Background

Transient increases in blood eosinophil count (BEC) have been observed in dupilumab clinical trials but are rarely associated with clinical symptoms.

Objective

We assessed the effect of early increases in BEC on long-term treatment outcomes.

Methods

Patients aged ≥12 years with moderate-to-severe type 2 asthma from the phase 3 QUEST study (NCT02414854; 52 weeks) who enrolled onto the TRAVERSE open-label extension study (NCT02134028; 96 weeks) were stratified by BEC: with or without ≥2-fold BEC increase any time by week 12 of QUEST, or presence or absence of increased BEC any time during QUEST (defined as < 500 cells/μL at baseline but ≥500 cells/μL at any time during QUEST). End points included annualized severe exacerbation rate and change from parent study baseline in prebronchodilator forced expiratory volume in 1 second (FEV ₁ ), 5-item Asthma Control Questionnaire, and type 2 inflammatory biomarkers.

Results

A total of 36.6% of dupilumab-treated patients versus 21.7% of placebo-receiving patients experienced a ≥2-fold BEC change by week 12, while 31.3% versus 28.0% experienced increased BEC any time during QUEST. Dupilumab versus placebo reduced annualized severe exacerbation rate, improved prebronchodilator FEV ₁ and questionnaire scores, and reduced biomarkers across subgroups at week 52 of QUEST. Improvements were maintained in all subgroups through week 96 of TRAVERSE.

Conclusions

Dupilumab reduced asthma exacerbations and improved lung function and asthma control up to 148 weeks in patients with uncontrolled moderate-to-severe type 2 asthma irrespective of early transient increases in BEC. Overall safety was consistent with the known dupilumab safety profile.

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Key words : Asthma, type 2, blood eosinophil count, dupilumab, F eno, exacerbations, lung function, biomarkers, efficacy, safety

Abbreviations used : ACQ-5, AER, BEC, CI, EGPA, F eno, FEV ₁, PSBL, SD, TARC, TEAE