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Crohn’s disease (CD) is a complex disease, and assessing activity is challenging due to pathobiologic process e.g. ECM remodeling, mucosal damage, and intestinal fibrosis, which greatly limits current disease activity assessments through e.g. endoscopy and imaging techniques. The review highlights the importance of novel biomarkers reflecting ECM remodeling and immune cell activity that accurately reflect CD activity and progression. Such biomarkers could include collagen formation and degradation fragments and a serum fragment of calprotectin, reflecting neutrophil activity. A new concept, fibro-inflammation, is also introduced in the review, in which all aspects of mucosal damage, such as inflammation, mucosal damage, tissue remodeling, intestinal fibrosis, and fibrosis resolution, should be assessed. PubMed searches performed from July 2022 – November 2022 provided the scientific information included in the review. Current data suggest intestinal fibrosis may sustain and exacerbate chronic inflammation, leading to non-response to anti-inflammatory treatments. Therefore, evaluating novel biomarkers reflecting different stages of fibro-inflammatory disease activity should be done in a clinical setting and considered for clinical trials. This approach will help accurately assess disease activity, leading to better management and treatment of CD.

Novel fibro-inflammatory biomarkers associated with disease activity in patients with Crohn’s disease