CHEST Pulmonary (Mar 2025)

Long-Term Efficacy of Dupilumab in Moderate-to-Severe Asthma Phenotyped by Blood Eosinophils and Exhaled Nitric OxideTake-home Points

  • Michael E. Wechsler, MD,
  • Ian D. Pavord, MD,
  • Alberto Papi, MD,
  • Kenneth R. Chapman, MD,
  • Arman Altincatal, MS,
  • Nami Pandit-Abid, PharmD,
  • Juby A. Jacob-Nara, MD,
  • Paul J. Rowe, MD,
  • Yamo Deniz, MD,
  • Elizabeth Laws, PhD,
  • Bolanle Akinlade, MD,
  • Nikhil Amin, MD,
  • Heribert W. Staudinger, MD,
  • David J. Lederer, MD,
  • Megan Hardin, MD

DOI
https://doi.org/10.1016/j.chpulm.2024.100072
Journal volume & issue
Vol. 3, no. 1
p. 100072

Abstract

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Background: Asthma treatment aims to reduce symptom severity and exacerbation risk. Dupilumab, a human monoclonal antibody, blocks the shared receptor for IL-4/IL-13, key drivers of type 2 inflammation. In the Evaluation of Dupilumab in Patients With Persistent Asthma (QUEST) study (NCT02414854), add-on dupilumab every 2 weeks vs placebo was shown to significantly reduce severe asthma exacerbations and improve prebronchodilator (BD) FEV1 in patients with uncontrolled, moderate-to-severe asthma. Treatment effects were greater in patients with elevated baseline type 2 biomarkers (blood eosinophil count ≥ 150 cells/μL or fractional exhaled nitric oxide ≥ 25 parts per billion). Research Question: What is dupilumab’s long-term efficacy (up to 3 years) in patients with moderate-to-severe type 2 asthma? Study Design and Methods: Patients enrolled in QUEST (receiving placebo or dupilumab), who completed 96 weeks of dupilumab treatment in the open-label extension Long-Term Safety Evaluation of Dupilumab in Patients With Asthma (TRAVERSE) study (NCT02134028), were included. This prespecified analysis evaluated long-term efficacy in patient populations identified by baseline type 2 biomarker level. End points were annualized exacerbation rate (AER) and change from baseline in pre-BD FEV1 (L), asthma control (5-item Asthma Control Questionnaire), and asthma-related quality of life (Asthma Quality of Life Questionnaire). Results: A total of 663 patients were included. AER was 1.72 to 2.24 at QUEST baseline in dupilumab groups across type 2 populations. AER decreased in populations with elevated type 2 biomarkers to 0.36 to 0.49 during QUEST’s 52-week treatment period, which was sustained over 96 weeks in TRAVERSE. In patients with low type 2 biomarker levels, there was no clinically meaningful AER reduction in QUEST or TRAVERSE, but rates remained below parent study baseline. Similar trends were seen with improvements in pre-BD FEV1, 5-item Asthma Control Questionnaire, and Asthma Quality of Life Questionnaire; greatest improvements were seen in groups with one or more elevated type 2 biomarker. Intrepretation: This study suggests that long-term dupilumab treatment results in sustained and clinically meaningful efficacy in patients with moderate-to-severe type 2 asthma characterized by elevated blood eosinophil count and/or fractional exhaled nitric oxide. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT02134028; URL: www.clinicaltrials.gov

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