Losartan Treatment Reduces Esophageal Eosinophilic Inflammation in a Subset of Eosinophilic Esophagitis.

Eosinophilic esophagitis esophageal transcriptome losartan quality of life symptom scores

Journal

The journal of allergy and clinical immunology. In practice
ISSN: 2213-2201
Titre abrégé: J Allergy Clin Immunol Pract
Pays: United States
ID NLM: 101597220

Informations de publication

Date de publication:
25 Jul 2024
Historique:
received: 28 05 2024
revised: 08 07 2024
accepted: 11 07 2024
medline: 27 7 2024
pubmed: 27 7 2024
entrez: 26 7 2024
Statut: aheadofprint

Résumé

Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE, therefore angiotensin II type 1 receptor (AT We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multi-site study. Fifteen participants, 5-23 years old, with EoE underwent treatment with a per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard-of-care therapy and 14 patients completed the study. Eosinophil counts served as the primary endpoint, while EoE Histology Scoring System (EoEHSS), Endoscopic Reference Scores (EREFS), EoE Diagnostic Panel (EDP), and patient-reported outcomes (PROs) were also assessed. Esophageal eosinophilia was not reduced following losartan. The peak eosinophil count was not reduced for the proximal (median (IQR): -3 (-22 to 3), p = 0.49) and distal esophagus (median (IQR): -18 (-39 to -1), p = 0.23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, a small subset of 4 participants resolved esophageal eosinophilia with concomitant reduction in EoEHSS and EREFS scores. Across all subjects, the Pediatric EoE Symptom Score and Pediatric Quality of Life Inventory EoE Module and EDP improved following losartan (p < 0.05). Losartan treatment associated with improved PRO scores and EDP biomarkers albeit without reducing esophageal eosinophilia overall. A subset of patients demonstrated improved histopathological and endoscopic features which could not be tied to a specific feature which could predict response to treatment.

Sections du résumé

BACKGROUND BACKGROUND
Eosinophilic esophagitis (EoE) is a chronic, food antigen-driven esophageal disorder. Connective tissue disorders (CTDs) and esophageal connective tissue alterations are associated with EoE, therefore angiotensin II type 1 receptor (AT
OBJECTIVE OBJECTIVE
We evaluated losartan's effects on esophageal pathology, symptoms, and safety in patients with EoE with and without a CTD in an open-label, non-placebo controlled multi-site study.
METHODS METHODS
Fifteen participants, 5-23 years old, with EoE underwent treatment with a per-protocol titrated doses of losartan in an open-label, 16-week pilot trial. Losartan was added to standard-of-care therapy and 14 patients completed the study. Eosinophil counts served as the primary endpoint, while EoE Histology Scoring System (EoEHSS), Endoscopic Reference Scores (EREFS), EoE Diagnostic Panel (EDP), and patient-reported outcomes (PROs) were also assessed.
RESULTS RESULTS
Esophageal eosinophilia was not reduced following losartan. The peak eosinophil count was not reduced for the proximal (median (IQR): -3 (-22 to 3), p = 0.49) and distal esophagus (median (IQR): -18 (-39 to -1), p = 0.23). There were no differences in losartan response in EoE with or without CTD (n = 7 and 8, respectively). Regardless, a small subset of 4 participants resolved esophageal eosinophilia with concomitant reduction in EoEHSS and EREFS scores. Across all subjects, the Pediatric EoE Symptom Score and Pediatric Quality of Life Inventory EoE Module and EDP improved following losartan (p < 0.05).
CONCLUSION CONCLUSIONS
Losartan treatment associated with improved PRO scores and EDP biomarkers albeit without reducing esophageal eosinophilia overall. A subset of patients demonstrated improved histopathological and endoscopic features which could not be tied to a specific feature which could predict response to treatment.

Identifiants

DOI: 10.1016/j.jaip.2024.07.011 PMID: 39059581
pubmed: 39059581
pii: S2213-2198(24)00742-6
doi: 10.1016/j.jaip.2024.07.011
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Auteurs

J Pablo Abonia (JP)

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Amanda K Rudman Spergel (AK)

Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland, USA.

Ikuo Hirano (I)

Division of Gastroenterology & Hepatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.

Tetsuo Shoda (T)

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Xue Zhang (X)

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Lisa J Martin (LJ)

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Vincent A Mukkada (VA)

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Philip E Putnam (PE)

Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Melodie Blacklidge (M)

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Derek Neilson (D)

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Margaret H Collins (MH)

Division of Pathology and Laboratory Medicine, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Department of Pathology & Laboratory Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Guang-Yu Yang (GY)

Division of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA.

Kelley E Capocelli (KE)

Division of Pathology, Children's Hospital Colorado, Aurora, Colorado, USA.

Heather Foote (H)

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Mike Eby (M)

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Stephanie Dong (S)

Division of Allergy Immunology, Rady Children's Hospital, University of California, San Diego, San Diego, California, USA.

Seema Aceves (S)

Division of Allergy Immunology, Rady Children's Hospital, University of California, San Diego, San Diego, California, USA. Electronic address: saceves@ucsd.edu.

Marc E Rothenberg (ME)

Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.

Classifications MeSH