Efficacy of Proton Pump Inhibitor Therapy for Eosinophilic Oesophagitis in 630 Patients

Results From the EoE Connect Registry

Emilio J. Laserna-Mendieta; Sergio Casabona; Danila Guagnozzi; Edoardo Savarino; Antonia Perelló; Antonio Guardiola-Arévalo; Jesús Barrio; Isabel Pérez-Martínez; Anne Lund Krarup; Javier Alcedo; Susana de la Riva; Esther Rey-Iborra; Cecilio Santander; Ángel Arias; Alfredo J. Lucendo

Disclosures

Aliment Pharmacol Ther. 2020;52(5):798-807. 

In This Article

Abstract and Introduction

Abstract

Background: Proton pump inhibitors (PPIs) are the most commonly used first-line therapy for patients with eosinophilic oesophagitis (EoE). However, many aspects related to PPIs in EoE are still unknown.

Aims: To assess the effectiveness of PPI therapy for EoE in real-world practice.

Methods: This cross-sectional study collected data on PPI efficacy from the multicentre EoE CONNECT database. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom score; histological remission was defined as a peak eosinophil count below 15 eosinophils per high-power field. Factors associated with effectiveness of PPI therapy were identified by binary logistic regression multivariate analyses.

Results: Overall, 630 patients (76 children) received PPI as initial therapy (n = 600) or after failure to respond to other therapies (n = 30). PPI therapy achieved eosinophil density below 15 eosinophils per high-power field in 48.8% and a decreased symptom score in 71.0% of patients. More EoE patients with an inflammatory rather than stricturing phenotype accomplished clinico-histological remission after PPI therapy (OR 3.7; 95% CI, 1.4–9.5); as well as those who prolonged treatment length from 8 to 12 weeks (OR 2.7; 95% CI, 1.3–5.3). After achieving clinico-histological remission of EoE, PPI dosage reduction was effectively maintained in 69.9% of patients, but tended to be less effective among those with a stricturing phenotype.

Conclusions: Inflammatory EoE phenotype and treatment duration up to 12 weeks correlated with greater chance for inducing remission of EoE. A stricturing phenotype decreased response rates to PPI therapy both initially and in the long term.

Introduction

Eosinophilic oesophagitis (EoE) is a chronic, immune-mediated inflammatory disease typically presenting with symptoms of oesophageal dysfunction and histologically characterised by a dense infiltration by eosinophils restricted to the oesophagus.[1] The natural history of EoE is defined by chronic or intermittent symptoms and persistence of inflammation over time,[2] which leads to oesophageal remodelling with collagen deposition, stricture formation and functional damage.[3,4] This fact, together with the impairment EoE produces on patients' health-related quality of life[5] indicates a need to treat symptomatic patients.

From being considered a refractory form of gastro-oesophageal reflux disease,[6] EoE was recognised early as a particular form of food allergy, triggered predominantly by food antigens,[7] and several modalities of dietary therapy demonstrated effectiveness in inducing disease remission.[8] In parallel, several trials showed that swallowed topic corticosteroids were also effective,[9,10] with oesophagus-targeted formulations providing better results.[11,12] Novel advanced therapies are being developed currently.[13] However, the aspect that has generated the most progress in the treatment of EoE in recent years is related to the use of proton pump inhibitors (PPIs).[14] Over the course of just a decade PPIs have gone from being an instrument to rule out gastro-oesophageal reflux disease as a cause of oesophageal eosinophilia,[15] to the defining factor of a new clinical entity called PPI-responsive oesophageal eosinophilia[16] and, finally, to constitute a true anti-inflammatory treatment for EoE.[1,17,18] The ability of PPIs to reduce both symptoms and eosinophilic infiltration in patients with EoE has been repeatedly documented.[19] The acid independent anti-inflammatory properties of PPIs were first demonstrated in EoE. PPI therapy significantly down-regulated oesophageal gene expression of eotaxin-3/CCL26 and T helper-2 cytokines interleukin (IL)-5 and IL-3 in biopsies from patients with EoE. This was also witnessed in patients treated with swallowed topic corticosteroids,[20] and both drugs showed overlapping effects in reversing the changes in the allergic oesophageal transcriptome that characterise EoE.[21]

The ability of PPIs to rid a moderate proportion of patients with EoE of inflammation and symptoms through a cheap and, in general, safe drug has contributed to placing them as a first-line option for the treatment of EoE in patients of all ages, at the same level of swallowed topic steroids and elimination diets,[1] and has made PPIs the most frequently used initial treatment option in real clinical practice.[22] However, many of the aspects related to the efficacy of PPIs in EoE are still unknown, largely because all the evidence to date has been provided by observational studies, generally involving small numbers of patients.[23]

Through an analysis of EoE CONNECT, the largest multicentre registry of patients with EoE, this study aims to provide data on the efficacy of PPI treatment for EoE in actual clinical practice, and to help clarify some of the questions that remain regarding this anti-inflammatory treatment approach.

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