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. 2025 Apr 15;4(3):100474.
doi: 10.1016/j.jacig.2025.100474. eCollection 2025 Aug.

Dupilumab efficacy in patients with type 2 asthma and early Feno level reductions

Ian D Pavord  1 , Michael E Wechsler  2 , William W Busse  3 , Christian Domingo  4 , Changming Xia  5 , Rebecca Gall  5 , Nami Pandit-Abid  6 , Juby A Jacob-Nara  6 , Amr Radwan  5 , Paul J Rowe  6 , Yamo Deniz  5
Affiliations

Dupilumab efficacy in patients with type 2 asthma and early Feno level reductions

Ian D Pavord et al. J Allergy Clin Immunol Glob. .

Abstract

Background: The QUEST (ClinicalTrials.gov identifier NCT02414854) and TRAVERSE (NCT02134028) studies demonstrated the efficacy of dupilumab, 200 or 300 mg, versus placebo every 2 weeks for 52 weeks (QUEST) and dupilumab, 300 mg, for an additional 96 weeks (TRAVERSE) in patients with uncontrolled, moderate-to-severe asthma.

Objective: This analysis assessed dupilumab efficacy in patients from QUEST who enrolled in TRAVERSE and were stratified by a reduction in fractional exhaled nitric oxide (Feno) level by week 2 of QUEST.

Methods: Patients with an Feno level of at least 25 ppb at parent study baseline (PSBL) were defined as those with or without a minimally important Feno level reduction/response (a ≥20% reduction in patients with an Feno level of ≥50 ppb and a reduction of >10 ppb in those with an Feno level of <50 ppb at PSBL) by week 2 of QUEST. We assessed annualized severe exacerbation rates (AERs) and changes from PSBL in prebronchodilator FEV1 value, 5-item Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score.

Results: During QUEST, dupilumab (compared with placebo) reduced AER by 58% to 59% across Feno response subgroups (unadjusted AER = 0.392-0.523 for dupilumab vs 1.052-1.280 for placebo) and improved prebronchodilator FEV1 value regardless of Feno response. These improvements were sustained during TRAVERSE, with a slightly greater magnitude in Feno responders. Dupilumab also improved 5-item Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores independently of Feno responses.

Conclusion: Dupilumab sustained efficacy for up to 3 years in patients with and without a minimally important early reduction in Feno level. Greater improvements were seen in patients with an early reduction in Feno level, but patients without such a reduction also showed favorable outcomes during their treatment with dupilumab.

Keywords: Dupilumab; Feno; asthma; asthma control; asthma exacerbation; asthma-related quality of life; early response; lung function.

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Conflict of interest statement

This research (registered under ClinicalTrials.gov identifiers NCT02414854 and NCT02134028) was sponsored by Sanofi and 10.13039/100009857Regeneron Pharmaceuticals Inc. The study sponsor was involved in the study design, conduct, analysis, and interpretation of the data. This article was written with assistance from an independent medical writing company funded by the study sponsors. Disclosure of potential conflict of interest: I. D. Pavord has received speaker fees from Aerocrine AB, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Novartis, Regeneron Pharmaceuticals Inc, Sanofi, and Teva Pharmaceuticals; payments for organizing educational events from AstraZeneca, GSK, Regeneron Pharmaceuticals Inc, Sanofi, and Teva Pharmaceuticals; acted as a consultant for Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Dey Pharma, Genentech, GSK, Knopp Biosciences, Merck, MSD, Napp Pharmaceuticals, Novartis, Regeneron Pharmaceuticals Inc, RespiVert, Sanofi, Schering-Plough, and Teva Pharmaceuticals; received international scientific meeting sponsorship from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, Napp Pharmaceuticals, Regeneron Pharmaceuticals Inc, Sanofi, and Teva Pharmaceuticals; and received a research grant from Chiesi. M. E. Wechsler has received personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, CytoReason, Equillium, Genentech, Genzyme, Novartis, PULMATRIX, Regeneron Pharmaceuticals Inc, resTORbio, Sentien Biotechnologies, and Teva and received grants and personal fees from GSK, and Sanofi. W. W. Busse has received consultant and speaker fees from AstraZeneca, Genentech, GSK, Novartis, Regeneron Pharmaceuticals Inc, and Sanofi. C. Domingo has received travel and speaker fees from ALK, Allergy Therapeutics, Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi, GSK, HAL Allergy, ImmunoTek, Menarini, Novartis, Sanofi, and Stallergenes Greer. C. Xia, R. Gall, A. Radwan, and Y. Deniz are employees and shareholders of Regeneron Pharmaceuticals Inc. N. Pandit-Abid and P .J. Rowe are employees of Sanofi and may hold stock and/or stock options in the company. J. A. Jacob-Nara is a former employee of Sanofi and may hold stock and/or stock options in the company.

Figures

Fig 1
Fig 1
Study design for the TRAVERSE open-label extension study (adapted from Wechsler et al7) showing only patients from QUEST who enrolled in TRAVERSE plus patient subgroups included in this post hoc analysis. QUEST patient numbers represent the numbers of patients enrolled in and exposed to treatment in TRAVERSE. Patients from QUEST enrolled in TRAVERSE the same day as the end-of-treatment visit. q2w, Every 2 weeks.
Fig 2
Fig 2
Unadjusted AERs∗ (A) and change from PSBL in prebronchodilator FEV1 values over time (B) in patients with QUEST baseline Feno levels of 25 ppb or higher who enrolled in TRAVERSE. ∗Total events during the observational period/total patient years followed. †Mean (SD). Severe asthma exacerbation events are defined as systemic corticosteroid (SCS) use for at least days or hospitalization/emergency room visit for asthma, requiring an SCS. PSBL = QUEST baseline; week 0 = TRAVERSE start. Feno responders are defined as patients achieving minimally important Feno level reductions at QUEST week 2. DPL, Dupilumab; PBO, placebo.
Fig 3
Fig 3
Change from PSBL in mean ACQ-5 (A) and AQLQ (B) scores in patients with QUEST baseline Feno levels of 25 ppb or higher who enrolled in TRAVERSE. PSBL = QUEST baseline. Feno responders are defined as patients achieving minimally important Feno level reductions at QUEST week 2.
Fig 4
Fig 4
Change from baseline in Feno level (ppb) in patients with QUEST baseline Feno levels of 25 ppb or higher who enrolled in TRAVERSE. Feno levels collected only during QUEST and not during TRAVERSE. PSBL is QUEST baseline. Feno responders are defined as patients achieving minimally important Feno level reductions at QUEST week 2.
See this image and copyright information in PMC

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