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

Marta S Alexdottir; Arno R Bourgonje; Morten A Karsdal; Martin Pehrsson; Roberta Loveikyte; Hendrik M van Dullemen; Marijn C Visschedijk; Eleonora A M Festen; Rinse K Weersma; Klaas Nico Faber; Gerard Dijkstra; Joachim H Mortensen

doi:10.3389/fmed.2022.933872

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

Front Med (Lausanne). 2022 Jul 12:9:933872. doi: 10.3389/fmed.2022.933872. eCollection 2022.

Affiliations

¹ Biomarkers and Research, Nordic Bioscience A/S, Herlev, Denmark.
² Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
³ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.

Abstract

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-α 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.

Keywords: Crohn’s disease; TNF-α antagonists; biomarkers; collagen; fibrosis; infliximab; surgery.