Current options and investigational drugs for the treatment of eosinophilic esophagitis

ABSTRACT

Introduction

Current treatments of eosinophilic esophagitis (EoE) induce symptomatic and histological remission in a proportion of patients. However, they do not fully meet patients’ needs and limitations should be acknowledged. The growing epidemiology of EoE has generated a great interest for research into novel therapeutic approaches.

Areas covered

This article discusses current therapies available for EoE, those under investigation and presents potential additional ones. Established anti-inflammatory treatments for EoE include dietary therapy, proton pump inhibitors, and swallowed topical corticosteroids, which are combined with endoscopic dilation in cases of strictures. Refractoriness, recurrence after treatment-cessation, and need for long-term therapies have encouraged investigation of novel, esophageal-targeted formulas of topical corticosteroids and of new therapeutic approaches directed at blocking the molecular pathways that lead to inflammation in EoE. These include monoclonal antibodies (including mepolizumab, reslizumab, benralizumab, dectrekumab, cendakimab, and dupilumab), JAK-STAT blockers, and S1PR agonists, among others. Some have provided evidence of effectiveness and safeness in the short-term use.

Expert opinion

Therapies under investigation potentially can target multiple Th2-associated diseases that converge in EoE patients. Therapeutic strategies require a personalized and patient-centered approach to reduce the burden of the disease, and cost-effectiveness analysis to position their use in a complex therapeutic landscape.

KEYWORDS:

• Eosinophilic esophagitis (EoE)
• swallowed topical corticosteroids
• budesonide
• fluticasone
• food-elimination diet
• proton pump inhibitor (PPI)
• biological therapy
• mepolizumab
• reslizumab
• benralizumab
• cendakimab
• dupilumab
• etrasimod

Article highlights

• The therapeutic goals in EoE include achieving clinical-histological and endoscopic remission, the prevention of remodelling-related complications and nutritional deficiencies, correcting eating/feeding dysfunction, and maintaining an adequate health-related quality of life.

• Current available therapies that have shown to achieve and maintain remission in EoE include diet, PPIs and swallowed topical corticosteroids. These can be combined with endoscopic dilation in cases of fibrostenotic complications. Any of these therapies needs to be used for the long term, as symptoms recurrence is usual after treatment cessation.

• The better understanding of the pathogenesis of EoE has allowed to identify new potential therapeutic targets.

• Considering that EoE is a Th2-mediated disease, monoclonal antibodies targeting interleukin (IL)-4, IL-13 and the α subunit of the IL-5 receptor (IL-5Rα), used for other Th2-mediated allergic diseases, are being investigated for EoE in late-phase clinical trial.

• Siglec-8 blockers able to induce eosinophil apoptosis, and etrasimod, an S1PR agonist, are also promising therapies to be incorporated into clinical practice.

• The treatment strategy needs to be individually agreed with the patient through a shared decision-making model, aiming to ensure adequate long-term monitoring and to meet patient’s needs.

This box summarizes key points contained in the article.

Acknowledgment

We are grateful to Melanie Radcliff for English language revision.

Declaration of interest

AJ Lucendo has received research funding from Adare/Ellodi, Dr Falk Pharma, and Regeneron; and has received consulting fees from Dr Falk Pharma and EsoCap.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One review receives grant support from Allakos, Arena, Bristol Myers Squibb, Lucid, Regeneron, and Takeda. They consult for Allakos, Bristol Myers Squibb, Lucid, Phathom, Regeneron, and Takeda. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.