Pharmacologic Treatment of Eosinophilic Esophagitis: Efficacious, Likely Efficacious, and Failed Drugs

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic, food allergen-mediated, esophageal disease that will lead, if left untreated, to esophageal remodeling. As such, the vast majority of EoE patients need treatment. Treatment strategies include drugs, food elimination diets, and esophageal dilation. This review focuses on pharmacologic options for treatment of EoE. Summary: Orodispersible budesonide tablets (Jorveza®) have been approved by regulatory authorities for EoE treatment of adults in Europe, Canada, and Australia, but not in the USA. Jorveza®, as compared to placebo, is effective in inducing and maintaining histologic and clinical remission over time. An orodispersible budesonide suspension (BOS, Eohilia®) was recently approved in the USA as induction treatment (12 weeks) in adolescents of at least 11 years and adults with active EoE. Before the approval of Jorveza® and Eohilia®, several investigator-initiated randomized controlled clinical studies evaluated esophagus-targeted formulations of either budesonide or fluticasone to treat pediatric and adult EoE patients. These drugs were generally efficacious in inducing and maintaining histological and clinical remission. Proton-pump inhibitors (PPIs) are used off-label for EoE treatment of pediatric and adult EoE patients given that they are able to induce histologic and clinical remission. However, when compared to the moderate certainty of evidence with regard to the failure to achieve histologic remission with swallowed topical corticosteroids, the certainty of evidence for PPIs is very low with very inconsistent results in absolute terms. Dupilumab (Dupixent®), a monoclonal antibody targeted against IL-4 and IL-13, was approved by regulatory authorities in the USA, Europe, Canada, but not yet Australia. In Europe, including Switzerland, Dupixent® is approved to treat EoE patients of at least 12 years of age with at least 40 kg body weight if they are either unresponsive or intolerant to or not candidates for conventional EoE therapies. Due to lack of efficacy or unfavorable safety profile, the following drugs are not recommended for EoE treatment: systemic steroids, sodium cromoglycate, montelukast, azathioprine, TNF-antagonists (e.g., infliximab), vedolizumab (mAb against α4β7), benralizumab (mAb against IL-5 receptor), mepolizumab (mAb against IL-5), reslizumab (mAb against IL-5), omalizumab (mAb against IgE), and lirentelimab (mAb against Siglec-8). Key Messages: Long-term effectiveness and safety data on different drugs are currently sparse. Concerted efforts of different stakeholders will be necessary to continue the endeavor of providing our patients with much-needed therapies.

Keywords

• eosinophilic esophagitis
• outcomes
• swallowed topical steroids
• proton-pump inhibitors
• dupilumab