Budesonide versus fluticasone for treatment of eosinophilic esophagitis

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DESCRIPTION (provided by applicant): Budesonide versus fluticasone for treatment of eosinophilic esophagitis ABSTRACT Eosinophilic esophagitis (EoE) is an emerging immune-mediated disease defined by abnormal infiltration of eosinophils into the esophageal mucosa, leading to dysphagia, progressive esophageal stenosis, and food impaction. Though initially thought to be rare, the incidence and prevalence are rising dramatically, and over the past decade EoE has rapidly become a major cause of upper gastrointestinal morbidity. The treatment of EoE, however, remains rudimentary and data are needed to inform practice. Corticosteroids are currently the mainstay of therapy for EoE, but there are no FDA-approved medications for EoE. Instead, asthma preparations are used, most commonly fluticasone in a multi-dose inhaler (MDI) or aqueous budesonide. These medications are swallowed, rather than inhaled, to coat the esophagus, but it is unknown whether fluticasone or budesonide is the most effective first line agent. It is also unknown how durable the response to these medications are, and whether baseline measurement of tissue biomarkers can predict treatment response. These are crucial and unanswered questions in EoE. We have recently conducted the first and only randomized trial directly comparing two topical formulations for treatment of EoE, and found that swallowing viscous slurry of budesonide was more effective than nebulizing and then swallowing an aqueous budesonide solution. However, viscous budesonide has never been directly compared with fluticasone, and these two medications are most commonly prescribed for EoE. We also have preliminary data showing that levels of major basic protein, eotaxin-3, and mast cell tryptase determined by immunohistochemical staining of esophageal biopsies predict treatment response. The specific aims of this project are 1) to determine whether viscous budesonide is more effective than fluticasone MDI for improving esophageal eosinophil counts and symptoms of dysphagia in patients with EoE after an initial treatment course; 2) to determine whether treatment with viscous budesonide results in less symptomatic and histologic recurrence than fluticasone MDI one year after the initial treatment course; and 3) to determine whether increased baseline staining of esophageal biopsies for major basic protein, eotaxin-3, and mast cell tryptase is associated with histologic response in EoE patients treated with topical corticosteroids. To achieve these aims, we will conduct a randomized, double-blind, clinical trial comparing viscous budesonide to fluticasone MDI. This innovative and hypothesis-driven study is backed by strong preliminary data generated by the PI while he was supported by an NIH career development award. It will be conducted by an established and unique multidisciplinary team with nationally recognized expertise in EoE, clinical trials, epidemiology, pathology, and translational science. The results will have a major clinical impact on the treatment algorithm for EoE by determining which medications doctors should use first and allowing them to predict treatment response. Data from this study will also readily lead to future trials of individualized treatment protocols for patients with EoE.