Drug treatment strategies for eosinophilic esophagitis in adults

ABSTRACT

Introduction

Eosinophilic esophagitis (EoE) is a clinical and pathological disorder, characterized by symptoms of esophageal dysfunction, and eosinophil-predominant inflammation restricted to the esophagus. Treatment outcomes include symptomatic remission, histological and endoscopic normalization and improving quality of life. Besides dietary modifications and endoscopic dilation, drugs available are swallowed topical corticosteroids (STCs) with reduced bioavailability and proton pump inhibitors (PPI).

Areas covered

Herein, the authors review the current treatment strategies for EoE in adults, providing the reader with their expert perspectives. The authors give discussion to the value of PPIs as a first-line therapy for EoE, in addition to the use of STCs. The current development of new formulations of STCs targeting the esophagus and novel therapies aimed at blocking molecular pathways are also discussed. Finally, the authors briefly look at the value of monoclonal antibodies targeting IL-5RA, IL-13, IL-4 or Siglec8, and oral S1PR agonists to the treatment of EoE.

Expert opinion

Viscose formulations of STC designed to coat the esophagus and new effervescent orodispersible tablets provide increased effectiveness at low doses. Investigational therapies that target several Th2-associated diseases seem useful in EoE. Comparative effectiveness and cost-utility analyses will help to position them in a complex therapeutic scenario.

KEYWORDS:

• Biological therapy
• benralizumab
• budesonide
• dupilumab
• cendakimab
• eosinophilic esophagitis
• etrasimod
• food-elimination diet
• fluticasone
• mepolizumab
• proton pump inhibitor
• reslizumab
• swallowed topical corticosteroids

Article highlights

• Eosinophilic esophagitis (EoE) is a chronic, immune-mediated esophageal disease, mainly triggered by exposure to dietary antigens and characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation restricted to the esophagus.

• Current therapeutic goals in eosinophilic esophagitis (EoE) in adults include symptomatic remission, histological normalization with (near) disappearance of eosinophilic inflammation, normalization of endoscopic features (especially the fibrotic effects of long-lasting inflammation), and restoring and maintaining adequate quality of life.

• Available anti-inflammatory therapies able to induce and maintain remission in EoE currently include dietary modifications, proton pump inhibitors and swallowed topical corticosteroids. In case of esophageal stricture or narrowing, they should be combined with endoscopic dilation. As the disease recurs after treatment cessation, long-term maintenance with the lowest effective dose of diet is required.

• Since there are no approved drugs to treat EoE in many setting, patients are usually treated with off-label preparations of topical corticosteroids, administered as nebulizer solutions, nasal drops, or metered-dose inhalers, which should be swallowed instead of inhaled, or by mixing the compound with different vehicles.

• Novel formulas of topical corticosteroids and devices designed to coat the esophageal mucosa and to deliver the medication into the esophagus increase the effectiveness in treating EoE. Budesonide orodispersible tablets are now available in several European countries to treat adult EoE patients.

• Monoclonal antibodies imported from other Th2-mediated allergic conditions that target interleukin (IL)-4, IL-13 and the α subunit of the IL-5 receptor (IL-5Rα) are now being investigated for EoE in late-phase clinical trials.

• Lirentelimab, a Siglec-8 blocker able to induce eosinophil apoptosis, and etrasimod, a S1PR agonist, are promising therapies to be incorporated into clinical practice.

Abbreviations

ACTH: adrenocorticotropic hormone; BOS: budesonide oral suspensión; CI: Confidence interval; DSQ: Dysphagia Symptom Questionnaire; EEsAI: Eosinophilic Esophagitis Activity Index; EMA: European Medicines Agency; EoE: eosinophilic esophagitis; EndoFLIP: endoscopic functional lumen image probe; EREFS: Edema, Rings, Exudates, Furrows, Stricture; FDA: Food and Drug Administration; GERD: gastroesophageal reflux disease; hpf: high-power field; HRQoL: Health-related quality of life; HSS: EoE Histology Scoring System; IL: interleukin; mAb: monoclonal antibody; P-CAB: Potassium-competitive acid blockers; PEESS: Pediatric EoE Symptom Score; PPI: proton pump inhibitors; PPI-REE: Proton pump inhibitor-responsive esophageal eosinophilia; PRO: patient reported outcomes; RCT: randomized controlled trial; STC: swallowed topic corticosteroids; S1P: Sphingosine-1-phosphate; S1PR: Sphingosine-1-phosphate receptor; Th2: T helper 2; TSLP: thymic stromal lymphopoietin; US: United States

Declaration of Interest

AJ Lucendo has served as speaker and/or has received research and/or educational funding or has received consultancy fees from Adare Pharmaceuticals/Ellodi Pharmaceuticals, Dr Falk Pharma, Regeneron and EsoCap. He has 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding This manuscript has not been funded.