Pharmacological treatments for eosinophilic esophagitis: current options and emerging therapies

ABSTRACT

Introduction: The epidemiology of eosinophilic esophagitis (EoE) has increased rapidly to represent a common cause of chronic and recurrent esophageal symptoms. Current treatment options have limitations so the development of novel therapies is a matter of growing interest.

Areas covered: This article provides an up-to-date discussion of current therapies and investigational options for EoE. Established anti-inflammatory treatments for EoE at present include dietary therapy, proton pump inhibitors and swallowed topic steroids, which should be combined with endoscopic dilation in case of strictures. Refractoriness, high recurrence rates, and need for long-term therapies have promoted the investigation of novel, esophageal-targeted formulas of topic corticosteroids, and monoclonal antibodies (including mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, infliximab, and vedolizumab) for EoE, with some having been demonstrated as effective and safe in the short term. Several additional promising therapies are also discussed.

Expert opinion: Several therapeutic targets have shown efficacy and will be approved to treat EoE, especially corticosteroid-sparing options and those for patients with multiple Th2-associated diseases. Personalized therapeutic strategies for initial and maintenance treatments of EoE must be rationally designed, to reduce the burden of disease and answer meaningfully the needs of all stakeholders involved in EoE.

KEYWORDS:

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

Article Highlights

• Therapeutic goals in EoE are evolving from the mere control of symptoms and eosinophilic inflammation to reversing and preventing fibrotic complications, guaranteeing nutritional status, and restoring or maintaining social relationships and quality of life.

• Current EoE treatments include diets that eliminate disease-triggering foods, PPIs, and various swallowed topical corticosteroid formulations, as well as endoscopic dilation in cases of reduced-gauge esophagus. Used appropriately they constitute an effective treatment to achieve and maintain the remission of EoE in a significant proportion of patients.

• Novel formulations of topic corticosteroids targeted to the esophageal mucosa are showing high rates of histological remission, both as inductions for maintenance therapy, and potentially allowing for small dose usage. Despite topic corticosteroids appearing to be safe in the long term, patient relapse is common when administration is stopped.

• New drugs under development, especially monoclonal antibodies, are being proposed to overcome the unmet medical needs of current EoE patients. Most are imported from other Th2-mediated allergic diseases and are being suggested as potentially having modifying effects on the natural history of the disease; however, this is yet to be demonstrated.

• After the failure of the anti-IgE antibody omalizumab and IL-5 blockers mepolizumab and reslizumab, anti-IL-13 drugs show some effectiveness. The IL-4 receptor antagonist dupilumab is the most promising option on the horizon, but several molecules acting over different points at the intimate mechanisms leading to EoE are also potential therapies.

• The availability of novel therapies for EoE will require re-designing rational and realistic strategies for initial and maintenance treatment of EoE, including patient-centered approaches and shared decision-making models. The goal is to overcome the limitations of current options while trying to answer meaningfully the needs of all stakeholders involved in EoE.

Declaration of interest

AJ Lucendo received honoraria as consultant at EsoCap Biotech and received research funding from Regeneron Pharmaceuticals, Inc., Adare Pharmaceuticals, Inc., and Dr. Falk Pharma, GmbH. The author 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

This paper was not funded.