Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy.
Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy.
Gastroenterology. 2018 Jul;155(1):76-87. doi: 10.1053/j.gastro.2018.03.032. Epub 2018 Mar 28.
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.
背景与目的:肠纤维化是克罗恩病(CD)患者治疗的一大挑战;因此,迫切需要加快开发针对这种疾病的抗纤维化药物。国际炎症性肠病组织(IOIBD)旨在确定一组终点指标,可用于评估在 CD 患者临床试验中测试的抗纤维化药物的疗效。
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 活动度和对治疗反应的临床、放射学、生化、内镜和综合终点指标,并确定其操作特性。一组 IOIBD 专家通过两轮在线 Delphi 式调查,进行共识过程,以确定纳入临床试验的最佳终点指标。
结果:共选择和评估了 36 个潜在与肠纤维化相关的终点指标。来自北美、欧洲、中东、亚太和拉丁美洲 5 个地区的 48 名具有炎症性肠病专业知识的医生参与了 Delphi 共识过程。一套核心的 13 个终点指标(完全临床缓解、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、无类固醇的临床缓解、治疗失败、深度缓解、完全无阻塞症状、无症状生存、肠损伤进展和无残疾)被评为关键指标。专家间的意见高度一致。
结论:IOIBD 成员就可用于评估 CD 患者抗纤维化药物的一组终点指标达成了专家共识。需要开展研究以明确这些结局的测量方法并验证测量工具。
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