Journal of Allergy and Clinical Immunology: Global (Aug 2025)

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

  • Ian D. Pavord, MD,
  • Michael E. Wechsler, MD,
  • William W. Busse, MD,
  • Christian Domingo, MD,
  • Changming Xia, PhD,
  • Rebecca Gall, MD,
  • Nami Pandit-Abid, PharmD,
  • Juby A. Jacob-Nara, MD, DHSc,
  • Amr Radwan, MBBChir,
  • Paul J. Rowe, MD,
  • Yamo Deniz, MD

DOI
https://doi.org/10.1016/j.jacig.2025.100474
Journal volume & issue
Vol. 4, no. 3
p. 100474

Abstract

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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.

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