Challenges in the Pathophysiology, Diagnosis, and Management of Intestinal Fibrosis in Inflammatory Bowel Disease

Abstract

Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) that is usually the consequence of chronic inflammation. Although the currently available anti-inflammatory therapies have had little impact on intestinal fibrosis in Crohn’s disease (CD), increased understanding of the pathophysiology and the development of therapies targeting fibrogenic pathways hold promise for the future. One of the critical challenges is how reduction or reversal of intestinal fibrosis should be defined and measured in the setting of clinical trials and drug approval.

The International Organization for Inflammatory Bowel Disease (IOIBD) organized a workshop in Amsterdam, The Netherlands, on December 19^th and 20^th, 2018 in an attempt to review the current knowledge of the biological background, diagnosis, treatment of intestinal fibrosis and clinical trial endpoints. Basic and clinical scientists discussed the pathophysiology of intestinal fibrosis, the current status of biomarkers and imaging modalities in stenosing CD, and recent clinical studies in this area. Researchers from outside of the IBD field presented advances in the understanding of fibrotic processes in other organs, such as the skin, liver and lungs. Lastly, the design of clinical trials with antifibrotic therapy for IBD was discussed, with priority on patient populations, patient reported outcomes (PROs) and imaging.

This report summarizes the key findings, discussions and conclusions of the workshop.

Figure 1.

Pathophysiology of intestinal fibrosis: Soluble factors (red) and different origins of mesenchymal cells (blue). CTGF: connective tissue growth factor; EGF, epidermal growth factor; EndoMT: endothelial-to-mesenchymal transition; ET: endothelins; PDGF: platelet-derived growth factor