Article Text
Abstract
Background Intestinal fibrosis resulting in stricture formation and obstruction in Crohn’s disease (CD) and increased wall stiffness leading to symptoms in ulcerative colitis (UC) is among the largest unmet needs in inflammatory bowel disease (IBD). Fibrosis is caused by a multifactorial and complex process involving immune and non-immune cells, their soluble mediators and exposure to luminal contents, such as microbiota and environmental factors. To date, no antifibrotic therapy is available. Some progress has been made in creating consensus definitions and measurements to quantify stricture morphology for clinical practice and trials, but approaches to determine the degree of fibrosis within a stricture are still lacking.
Objective We herein describe the current state of stricture pathogenesis, measuring tools and clinical trial endpoints development.
Design Data presented and discussed in this review derive from the past and recent literature and the authors’ own research and experience.
Results and conclusions Significant progress has been made in better understanding the pathogenesis of fibrosis, but additional studies and preclinical developments are needed to define specific therapeutic targets.
- fibrosis
- inflammatory bowel disease
- myofibroblasts
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Footnotes
Contributors Contributed to planning: FR. Contributed to conduct, and reporting of the work described in the article, data collection, analysis, writing the paper, editing manuscript: all authors. Contributor(s) as being responsible for the overall content as guarantor(s): FR.
Funding This work was supported by the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research (STAR) Consortium (No. 3081 to FR), the National Institute of Health (NIDDK R01DK123233 and R01DK132038 to FR), and the National Institute of Health (NIDDK 2 P30 DK097948) to CF and FR.
Competing interests PM, WJM and YW have no conflict of interest. CF received speaker fees from UCB, Genentech, Sandoz, Janssen and he is consultant for Athos Therapeutics. FR is consultant to Agomab, Allergan, AbbVie, Boehringer-Ingelheim, Celgene, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Jansen, Koutif, Metacrine, Morphic, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Takeda, Techlab, Thetis, UCB, 89Bio.
Provenance and peer review Commissioned; externally peer reviewed.