Background & Aims

There is no consensus on the best way to integrate biomarkers into inflammatory bowel disease (IBD) research and clinical practice. The International Organization for the Study of Inflammatory Bowel Disease (IOIBD) aimed to outline biomarker definitions, categories, and operating properties required for their use in registration trials and clinical practice. Using fecal calprotectin as an example, we provide a framework for biomarker development and validation in patients with IBD.

Methods

We reviewed international society guidelines, regulatory agency guidance documents, and standardized reporting guidelines for biomarkers, in combination with publications on fecal calprotectin levels in patients with IBD. We assessed the validity of fecal calprotectin to serve as a surrogate biomarker of IBD activity and outlined a framework for further validation and development of biomarkers.

Results

No endpoints have been fully validated as surrogates of risk of disease complications—mucosal healing is the most valid endpoint used to determine risk of disease complications. Fecal level of calprotectin has not been validated as a biomarker for IBD activity, due to lack of technical and clinical reliability, assessment of performance when used as a replacement for endoscopy, and assessment of responsiveness to changes in disease states. The level of fecal calprotectin can be used only as a prognostic factor for disease recurrence in patients in remission following medical or surgical treatment.

Conclusions

We reviewed guidelines, regulatory documents, and publications to identify properties required for development of biomarkers of IBD activity and areas in need of clarification from regulatory agencies and societies. We propose a path forward for research of biomarkers for IBD.

中文翻译：

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将生物标志物纳入临床试验和护理途径的方法，作为治疗炎症性肠病的靶标

背景与目标

关于将生物标志物整合入炎症性肠病（IBD）研究和临床实践的最佳方法尚无共识。国际炎症性肠病研究组织（IOIBD）旨在概述生物标志物的定义，类别和在注册试验和临床实践中使用所需的操作特性。以粪钙卫蛋白为例，我们为IBD患者的生物标志物开发和验证提供了框架。

方法

我们结合有关IBD患者粪便钙卫蛋白水平的出版物，回顾了国际社会指南，监管机构指南文件和生物标志物的标准化报告指南。我们评估了粪便钙卫蛋白作为IBD活性替代生物标志物的有效性，并概述了进一步验证和开发生物标志物的框架。

结果

没有任何终点可以作为疾病并发症风险的替代指标得到充分验证—粘膜愈合是用于确定疾病并发症风险的最有效终点。由于缺乏技术和临床可靠性，用作内窥镜检查的替代品时的性能评估以及对疾病状态变化的响应性评估，粪便中钙卫蛋白的水平尚未被确认为IBD活性的生物标志物。粪钙卫蛋白的水平只能用作药物或手术治疗缓解后患者疾病复发的预后因素。

结论

我们审查了指南，监管文件和出版物，以确定开发IBD活动生物标志物所需的特性以及监管机构和社会需要澄清的领域。我们为IBD生物标志物的研究提出了一条前进的道路。