Symptomatic Improvement in Adults and Adolescents With Eosinophilic Esophagitis Requires Higher Systemic Dupilumab Exposure Than Histologic Response

Clin Transl Gastroenterol. 2025 Jan 1;16(1):e00793. doi: 10.14309/ctg.0000000000000793.

Abstract

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.

Discussion: The dupilumab 300 mg weekly regimen approved for adults and adolescents with EoE weighing ≥ 40 kg is supported by dose- and exposure-response relationships.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Eosinophilic Esophagitis* / diagnosis
  • Eosinophilic Esophagitis* / drug therapy
  • Eosinophilic Esophagitis* / immunology
  • Eosinophilic Esophagitis* / pathology
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Esophagus / immunology
  • Esophagus / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Treatment Outcome
  • Young Adult

Substances

  • dupilumab
  • Antibodies, Monoclonal, Humanized