Emerging drugs for eosinophilic esophagitis.
BACKGROUND
Eosinophilic esophagitis (EoE) has emerged over the past two decades as an important esophageal disorder with significant associated morbidity. The prevalence of EoE now approximates that of commonly recognized gastrointestinal diseases including inflammatory bowel disease. In adults, EoE is now a leading cause of dysphagia and food impaction. Medications, food elimination diets and esophageal dilation are currently utilized for the treatment of EoE. While these approaches are often effective, no pharmaceutical agents have yet been approved by the Food and Drug Administration (FDA). The current medical therapies for EoE primarily consist of topical corticosteroids that have been adopted from formulations designed for pulmonary delivery in patients with asthma and have not been optimized for esophageal delivery.


METHODS
This article focuses on therapeutics being developed for EoE. Several trials have evaluated improved steroid vehicles designed for topical delivery to the esophagus. Novel biologic compounds, including anti-interleukin-5 and anti-interleukin-13, are being evaluated as targeted treatment options in EoE patients. Inhibitors of mast cell-derived prostaglandin D2 (PGD2) are also being studied, based on the concept that mast cells play an important role in EoE pathogenesis. Additional therapies, including immunomodulators, leukotriene antagonists, allergy immunotherapy and angiotensin II receptor blockers, are also examined in this article.


CONCLUSIONS
No FDA-approved prescription medications are currently available for EoE patients. Although a number of novel agents are being developed and tested, Phase III clinical trials are scarce. Since EoE is a newly described disease, physicians have an incomplete understanding of the disease's pathogenesis, natural history and disease manifestations. This has led to significant difficulties in determining the most appropriate endpoints of therapy. Clinical trials are hampered by the lack of an accepted, standardized disease activity measure or biomarker by which therapeutic efficacy is assessed. Effective and approved pharmaceutical therapies are eagerly awaited by both physicians and patients for this increasingly recognized and clinically important disease.
Northwestern University Feinberg School of Medicine, Division of Gastroenterology, Chicago, IL 60611, USA.
Emily
E
Kern
Ikuo
I
Hirano
D000287:Administration, Topical; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D057765:Eosinophilic Esophagitis / Q000628:therapy*; D005247:Feeding Behavior; D006801:Humans; D054328:Proton Pump Inhibitors / Q000627:therapeutic use
D000305:Adrenal Cortex Hormones; D054328:Proton Pump Inhibitors