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Dupilumab normalizes the eosinophilic esophagitis disease transcriptome.

Wei Keat Lim1, Matthew F Wipperman1, Marc E Rothenberg2

  • 1Regeneron Pharmaceuticals Inc, Tarrytown, NY.

The Journal of Allergy and Clinical Immunology
|April 24, 2026
PubMed
Summary

Dupilumab treatment normalized the esophageal transcriptome in patients with eosinophilic esophagitis (EoE), addressing type 2 inflammation and esophageal dysfunction. These improvements were sustained across all age groups.

Keywords:
Eosinophilic esophagitisdupilumabgene expressiontranscriptometype 2 inflammation

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Area of Science:

  • Molecular biology and immunology of esophageal diseases.
  • Transcriptomics and gene expression analysis in inflammatory conditions.
  • Pharmacology of targeted biologic therapies.

Background:

  • Eosinophilic esophagitis (EoE) is a type 2 inflammatory disease (T2ID) of the esophagus.
  • EoE is characterized by eosinophilic inflammation and an altered esophageal transcriptome.
  • Dupilumab, a monoclonal antibody blocking IL-4 and IL-13, is approved for EoE and other T2IDs.

Purpose of the Study:

  • To investigate the effect of dupilumab on the dysregulated esophageal transcriptome in EoE.
  • To analyze transcriptome changes in pediatric, adolescent, and adult EoE patients treated with dupilumab.

Main Methods:

  • Analysis of esophageal biopsies from EoE patients before and after dupilumab treatment.
  • Utilized data from three placebo-controlled clinical trials involving dupilumab.
  • Transcriptome changes were assessed across pediatric, adolescent, and adult patient groups.

Main Results:

  • Dupilumab treatment normalized the EoE disease transcriptome, including gene signatures for eosinophils, mast cells, and fibrosis.
  • Gene ontology analysis revealed normalization of 41 biologic processes, some independent of eosinophils.
  • Transcriptome changes were comparable and sustained through week 52 in all age groups.

Conclusions:

  • Interleukin-4 (IL-4) and IL-13 are key drivers of molecular differences in EoE esophageal mucosa.
  • Dupilumab's clinical benefit in EoE is consistent with its effect on IL-4/IL-13 signaling.
  • The study supports IL-4/IL-13 as critical targets for EoE treatment.