4.6 Article

Serological Biomarkers of Intestinal Collagen Turnover Identify Early Response to Infliximab Therapy in Patients With Crohn's Disease

Journal

FRONTIERS IN MEDICINE
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmed.2022.933872

Keywords

Crohn's disease; infliximab; TNF-alpha antagonists; biomarkers; collagen; fibrosis; surgery

Funding

  1. Junior Scientific Masterclass (JSM), University of Groningen, Netherlands [17-57]
  2. Danish Research Foundation

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This study aimed to assess the role of serological biomarkers in monitoring and predicting treatment response in patients with Crohn's disease undergoing infliximab induction therapy. The results showed that baseline levels of a biomarker for type IV collagen degradation were associated with treatment response, while biomarkers for type III and VI collagen formation could be used to monitor response at the end of treatment. Additionally, biomarker ratios for type IV collagen turnover showed promising results in monitoring treatment response in patients without a surgical history.
Background: Crohn's disease (CD) is characterized by excessive protease activity and extracellular matrix (ECM) remodeling. To date, 30-50% of patients experience non-response to anti-TNF-alpha treatment. This study aimed to assess whether serological biomarkers of ECM turnover could monitor or predict response to infliximab (IFX) induction therapy in patients with and without a surgical history. Methods: Serum biomarkers of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen degradation, type III (PRO-C3) and VI (PRO-C6) collagen formation, basement membrane turnover (PRO-C4), and T-cell activity (C4G), were measured at baseline and week 14, in 63 patients with CD undergoing IFX induction therapy. Patients were stratified according to surgical history. Results: C4M was elevated at baseline in responders with a surgical history (n = 10) and associated with response at baseline (P < 0.05). Additionally, C6Ma3, PRO-C3, and PRO-C6 were elevated at week 14 in responders compared with non-responders (n = 8) and could differentiate between the two groups (P < 0.05). Two biomarker ratios (C4M/C4G and PRO-C4/C4G) were elevated at week 14 in non-responders (n = 5) without a surgical history compared with responders (n = 40) and could differentiate between the response groups (P < 0.05). Conclusion: Baseline levels of a serological biomarker for type IV collagen degradation associated with response to IFX induction therapy, and biomarkers of type III and VI collagen formation may be used to monitor response at the end of induction therapy in patients with a surgical history. Biomarker ratios of type IV collagen turnover demonstrated promising results in monitoring treatment response in patients without a surgical history.

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