Northwestern University Feinberg School of Medicine, Division of Gastroenterology, Chicago, IL 60611, USA.
Expert Opin Emerg Drugs. 2013 Sep;18(3):353-64. doi: 10.1517/14728214.2013.829039. Epub 2013 Aug 13.
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.
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.
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.
嗜酸性食管炎 (EoE) 在过去二十年中作为一种重要的食管疾病出现，其相关发病率显著。EoE 的患病率现在与常见的胃肠道疾病（包括炎症性肠病）相当。在成年人中，EoE 现在是吞咽困难和食物嵌塞的主要原因。药物、食物消除饮食和食管扩张目前用于治疗 EoE。虽然这些方法通常是有效的，但还没有一种药物制剂被食品和药物管理局 (FDA) 批准。EoE 的当前医疗疗法主要包括局部皮质类固醇，这些皮质类固醇是从为哮喘患者设计的肺部给药制剂中采用的，并且尚未针对食管给药进行优化。
本文重点介绍正在开发用于治疗 EoE 的疗法。几项试验评估了旨在用于食管局部递送的改良皮质类固醇载体。新型生物化合物，包括抗白细胞介素-5 和抗白细胞介素-13，正在作为 EoE 患者的靶向治疗选择进行评估。基于肥大细胞在 EoE 发病机制中起重要作用的概念，也正在研究肥大细胞衍生的前列腺素 D2 (PGD2) 抑制剂。本文还研究了其他治疗方法，包括免疫调节剂、白三烯拮抗剂、过敏免疫疗法和血管紧张素 II 受体阻滞剂。
目前尚无 FDA 批准的处方药物可用于 EoE 患者。尽管有许多新型药物正在开发和测试，但 III 期临床试验很少。由于 EoE 是一种新描述的疾病，医生对该疾病的发病机制、自然病史和疾病表现了解不完整。这导致在确定最适当的治疗终点方面存在重大困难。由于缺乏公认的标准化疾病活动测量或生物标志物来评估治疗效果，临床试验受到阻碍。对于这种越来越被认识和具有重要临床意义的疾病，医生和患者都急切地等待有效的批准药物治疗。
