Identification of Endpoints for Development of Antifibrosis Drugs for Treatment of Crohn's Disease
Identification of Endpoints for Development of Antifibrosis Drugs for Treatment of Crohn's Disease
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DOI：
10.1053/j.gastro.2018.03.032
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发表时间：
2018-07-01
期刊：
影响因子：
29.4
通讯作者：
Peyrin-Biroulet, Laurent
中科院分区：
文献类型：
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作者：
Danese, Silvio;Bonovas, Stefanos;Peyrin-Biroulet, Laurent
背景与目的：肠纤维化是克罗恩病（CD）患者治疗的一个挑战；目前迫切需要加快针对这种疾病的抗纤维化药物的开发。国际炎症性肠病研究组织（IOIBD）旨在确定一组可用于确定CD患者临床试验中抗纤维化药物疗效的终点。方法：我们进行了一项系统综述，以确定用于评估纤维狭窄性CD活性和治疗反应的临床、放射学、生化、内镜和复合终点，并确定其操作特性。IOIBD专家小组通过两轮德尔菲式在线调查，达成共识，以确定纳入临床试验的最佳终点。结果：共选择并评估了36个肠纤维化的潜在相关终点。来自5个地区（北美、欧洲、中东、亚洲/太平洋和拉丁美洲）的48名具有炎症性肠病专业知识的医生参加了德尔菲共识过程。13个核心终点（完全临床反应、长期疗效、持续临床获益、治疗失败、放射学缓解、正常生活质量、不使用类固醇的临床缓解、治疗失败、深度缓解、完全无闭塞症状、无症状生存、肠损伤进展和无残疾）被评为关键。专家们的意见非常一致。结论：IOIBD成员就一组可用于评估CD患者试验中抗纤维化药物的终点达成了专家共识。需要研究来阐明测量这些结果的方法并验证测量仪器。
BACKGROUND & AIMS: Intestinal fibrosis is a challenge to management of patients with Crohn's disease (CD); there is an urgent need to expedite development of antifibrosis drugs for this disease. The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) aimed to identify a set of endpoints that can be used to determine efficacy of antifibrosis agents tested in clinical trials of patients with CD. METHODS: We conducted a systematic review to identify clinical, radiologic, biochemical, endoscopic, and composite endpoints used in assessing activity of fibrostenosing CD and response to treatment, and determined their operational properties. A panel of IOIBD experts performed a consensus process to identify the best endpoints for inclusion in clinical trials, through a 2-round, Delphi-style online survey. RESULTS: A total of 36 potentially relevant endpoints for intestinal fibrosis were selected and assessed. Forty-eight physicians with expertise in inflammatory bowel disease, from 5 regions (North America, Europe, Middle East, Asia/Pacific, and Latin America), participated in the Delphi consensus process. A core set of 13 endpoints (complete clinical response, long-term efficacy, sustained clinical benefit, treatment failure, radiological remission, normal quality of life, clinical remission without steroids, therapeutic failure, deep remission, complete absence of occlusive symptoms, symptom-free survival, bowel damage progression, and no disability) were rated as critical. Agreement was high among the experts. CONCLUSIONS: Members of the IOIBD reached expert consensus on a set of endpoints that can be used to assess antifibrosis agents in trials of patients with CD. Studies are needed to clarify methods for measuring these outcomes and validate measurement instruments.