Division of Gastroenterology and Inborn Errors Products, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
J Allergy Clin Immunol. 2012 Sep;130(3):613-6. doi: 10.1016/j.jaci.2012.07.011. Epub 2012 Jul 31.
Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives.
与许多罕见疾病一样，嗜酸性食管炎 (EoE) 是一种了解甚少的疾病，长期以来，用于准确确定疾病活动度、缓解和自然病史的评估工具一直不足。能够评估候选治疗药物在临床试验中有效性的临床结局终点一直是一个特别的不足之处，迫切需要这样的工具。由于患者没有可用的治疗方法，而且 EoE 的患病率不断增加，因此合作开发药物的方法变得越来越重要。我们描述了过去 18 个月内在机构之间调动的一项合作努力，专门针对进一步开展 EoE 病因和治疗临床研究的需求。合作者包括北美儿科学会、胃肠病学、肝脏病学和营养学分会；国际胃肠道嗜酸性粒细胞研究人员；以及美国食品和药物管理局。这项工作阐明了几个对于 EoE 登记试验有效的参数，包括需要有临床意义的终点，除了评估上皮内黏膜嗜酸性粒细胞之外，还要衡量临床症状的变化。生物标志物的开发和使用，特别是在药物早期开发阶段，已成为调查的重要焦点，这可能会减少对临床对连续侵入性监测的依赖。这里描述的协同努力旨在制定合理的治疗方法和药物开发范例，这似乎也为罕见疾病药物开发背景下的有效合作，以及更普遍的公共卫生计划提供了一个模式。
