Budesonide versus fluticasone for treatment of eosinophilic esophagitis

布地奈德与氟替卡松治疗嗜酸性粒细胞性食管炎

基本信息

批准号：
8856230
负责人：
Evan Samuel Dellon
金额：
$ 33.06万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8856230
关键词：
Address Adrenal Cortex Hormones Aftercare Algorithms Anti-Inflammatory Agents Anti-inflammatory Asthma Preparation Back Biological Markers Biopsy Breathing Budesonide Caring Clinic Clinical Clinical Trials Data Deglutition Deglutition Disorders Diagnosis Disease Dose Double-Blind Method Drug Formulations Eosinophilia Eosinophilic Esophagitis Epidemiology Esophageal Esophageal Stenosis Esophageal mucous membrane Esophagus FDA approved Food Future Genetic Determinism Goals Health Histologic Immune Incidence Infiltration Inflammation Inhalators K-Series Research Career Programs Lead Measurement Mediating Methods Morbidity - disease rate Pathology Patients Pharmaceutical Preparations Prevalence Proteins Randomized Recurrence Research Sampling Solutions Staining method Stains Steroid therapy Steroids Symptoms Testing Tissues Topical Corticosteroids Translational Research Treatment Protocols Tryptase United States National Institutes of Health aqueous base clinical practice eosinophil fluticasone gastrointestinal human CCL26 protein improved individualized medicine innovation multidisciplinary prospective randomized trial response treatment duration treatment effect treatment response treatment strategy trial comparing

项目摘要

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.

描述（由申请人提供）：布地奈德与氟替卡松治疗嗜酸性粒细胞性食管炎摘要嗜酸性粒细胞性食管炎（EoE）是一种新兴的免疫介导疾病，其定义为嗜酸性粒细胞异常浸润食管粘膜，导致吞咽困难、进行性食管狭窄和食物嵌塞。尽管最初被认为很罕见，但其发病率和患病率正在急剧上升，并且在过去十年中 EoE 已迅速成为上消化道发病的主要原因。然而，EoE 的治疗仍然处于初级阶段，需要数据来指导实践。皮质类固醇目前是 EoE 的主要治疗方法，但 FDA 还没有批准治疗 EoE 的药物。相反，使用哮喘制剂，最常见的是多剂量吸入器 (MDI) 中的氟替卡松或布地奈德水溶液。这些药物是吞咽而不是吸入，以覆盖食道，但尚不清楚氟替卡松或布地奈德是否是最有效的一线药物。目前还不清楚这些药物的反应有多持久，以及组织生物标志物的基线测量是否可以预测治疗反应。这些是 EoE 中至关重要且尚未解答的问题。我们最近进行了第一个也是唯一一个直接比较两种外用制剂治疗 EoE 的随机试验，发现吞咽布地奈德粘稠浆液比雾化然后吞咽布地奈德水溶液更有效。然而，粘性布地奈德从未与氟替卡松进行直接比较，这两种药物最常用于治疗 EoE。我们还有初步数据显示，通过食管活检免疫组织化学染色确定的主要碱性蛋白、eotaxin-3 和肥大细胞类胰蛋白酶的水平可预测治疗反应。该项目的具体目标是 1) 确定粘性布地奈德是否比氟替卡松 MDI 更有效地改善 EoE 患者在初始治疗过程后的食管嗜酸性粒细胞计数和吞咽困难症状； 2) 确定初始治疗一年后，粘性布地奈德治疗是否比氟替卡松 MDI 治疗更少症状和组织学复发； 3) 确定食管活检中主要碱性蛋白、eotaxin-3 和肥大细胞类胰蛋白酶的基线染色增加是否与接受局部皮质类固醇治疗的 EoE 患者的组织学反应相关。为了实现这些目标，我们将进行一项随机、双盲临床试验，比较粘性布地奈德和氟替卡松 MDI。这项创新性和假设驱动的研究得到了 PI 生成的强有力的初步数据的支持，同时他还获得了 NIH 职业发展奖的支持。它将由一个成熟且独特的多学科团队进行，该团队在 EoE、临床试验、流行病学、病理学和转化科学方面拥有全国公认的专业知识。结果将对治疗算法产生重大临床影响 EoE 通过确定医生应该首先使用哪些药物并允许他们预测治疗反应。这项研究的数据也将很容易用于未来针对 EoE 患者的个体化治疗方案的试验。