Parambir S Dulai1, Laurent Peyrin-Biroulet2, Silvio Danese3, Bruce E Sands4, Axel Dignass5, Dan Turner6, Gerassimos Mantzaris7, Juergen Schölmerich8, Jean-Yves Mary9, Walter Reinisch10, William J Sandborn11. 1. Division of Gastroenterology, University of California San Diego, La Jolla, California. Electronic address: pdulai@ucsd.edu. 2. Department of Gastroenterology, Nancy University Hospital, Lorraine University, Nancy, France. 3. Department of Biomedical Sciences, Humanitas University, Humanitas Clinical and Research Centre, Milan, Italy. 4. Dr Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York. 5. Department of Medicine I, Agaplesion Markus Hospital and Crohn Colitis Clinical Research Center Rhein-Main, Frankfurt/Main, Germany. 6. Institute of Paediatric Gastroenterology, Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel. 7. Department of Gastroenterology, Evaggelismos-Ophthalmiatreion Athinon-Polycliniki, Athens, Greece. 8. Goethe University, Frankfurt, Germany. 9. INSERM UMR, Paris Diderot University, Saint Louis Hospital, Paris, France. 10. Universitätsklinik für Innere Medizin III, Vienna, Austria. 11. Division of Gastroenterology, University of California San Diego, La Jolla, California.
Abstract
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 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 because of 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 after medical or surgical treatment. CONCLUSIONS: We reviewed guidelines, regulatory documents, and publications to identify properties required for the 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.
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 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 because of 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 after medical or surgical treatment. CONCLUSIONS: We reviewed guidelines, regulatory documents, and publications to identify properties required for the 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.
Authors: Christoph Kessel; Miha Lavric; Toni Weinhage; Markus Brueckner; Sytze de Roock; Jan Däbritz; Jakob Weber; Sebastiaan J Vastert; Dirk Foell Journal: Sci Rep Date: 2021-03-23 Impact factor: 4.379