An allergen-specific immune signature-directed diet vs sham diet for treatment of eosinophilic esophagitis: A pilot-feasibility study

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An allergen-specific immune signature-directed diet vs sham diet for treatment of eosinophilic esophagitis: A pilot-feasibility study ABSTRACT Eosinophilic esophagitis (EoE) is a chronic disease defined by abnormal infiltration of eosinophils into the esophageal mucosa, leading to dysphagia, progressive esophageal stenosis, and food impaction. The incidence and prevalence are rising dramatically, and EoE is now a major cause of upper gastrointestinal morbidity. Because EoE is allergen-mediated and triggered by foods, dietary elimination is the primary non- pharmacologic treatment. However, the approach to dietary elimination is sub-optimal, burdensome, and time- consuming. Currently available blood- or skin-based allergy tests do not reliably identify food triggers of EoE, so multiple foods must be empirically removed from the diet. Adherence to these restrictive diets is difficult, the same approach is used for all patients, and foods that are not eliminated may still be triggers. Multiple endoscopies are required to identify triggers, and these invasive and costly procedures carry risks. Two major issues must be addressed to allow widespread application of dietary therapy in EoE. First, if accurate allergy tests were available, treatment could be personalized and streamlined. Foods likely to be triggers in an individual patient could be eliminated, and foods unlikely to provoke eosinophilic inflammation could be retained. Second, if non-invasive biomarkers were available to monitor treatment response, the need for endoscopies could be greatly reduced. To begin to address these two major knowledge gaps, we developed a novel allergen-specific immune signature to guide dietary elimination. This technique predicts food triggers based on food-specific IgG4 levels in esophageal biopsies and CD4+ T-cell stimulation assays in peripheral blood. In initial testing, this approach was more accurate than traditional skin-based allergy tests. We have also identified a promising biomarker, eosinophil peroxidase (EPX), that can be measured in the serum and tracks with treatment response as measured on esophageal biopsies. The proposed study has been designed to be highly responsive to PAS 20-160, a new “small R01” mechanism that encourages pilot/feasibility clinical trials that lay the foundation for larger trials. To generate key data to estimate effect sizes, we will conduct a pilot randomized clinical trial of the allergen-specific immune signature-directed diet elimination vs sham diet elimination with the following specific aims: 1) To estimate the effect of allergen-specific immune signature- directed dietary elimination compared to sham elimination on esophageal eosinophil counts and symptoms of dysphagia in patients with EoE; and 2) To assess serum EPX as a non-invasive biomarker and estimate effect sizes for monitoring dietary elimination treatment response in patients with EoE. This innovative pilot/feasibly trial will be conducted by an existing multidisciplinary team with recognized expertise in EoE, clinical trials, food allergy, pathology, and translational science. It will ultimately lead to a major clinical impact on the treatment and monitoring of EoE by individualizing dietary elimination and streamlining monitoring of dietary elimination using non-invasive biomarkers, so patients can avoid the time, effort, and risk of empiric dietary elimination.