Abstract Background Therapeutic sequencing remains a challenge in the management of ulcerative colitis. We investigated if extracellular matrix (ECM) biomarkers predict short- and long-term vedolizumab (VDZ) treatment outcomes following anti-TNF treatment failure to aid selection of appropriate candidate patients for this order of biologic sequencing. Methods Blood samples obtained from our biobank was used to assess ECM biomarker profiles at time of anti-TNF failure (n = 58) and at baseline (n = 47) immediately prior to initiation of VDZ therapy. VDZ treatment outcomes assessed at 3 and 12 months was clinical remission (CR) (SCCAI £2 or pMayo £2), clinical response (reduction in SCCAI ³3) and objective remission (OR) assessed at 12 months (Mayo endoscopic score £1 (n = 41), faecal calprotectin 200mg/g (n = 14), and no signs of disease activity on clinical imaging (n = 1)). ECM biomarkers covered neutrophil activity (CPa9-HNE), collagen type III and type IV degradation mediated by matrix metalloproteinase-9 activity (C3M and C4M respectively) and collagen type III degradation through inflammation associated fibroblast (IAF) activity (C3F), degradation of cross-linked type III collagen (CTX-III), fibroblast activity and type III, VI (PRO-C3 and PRO-C6 respectively) and XXII collagen formation (PRO-C22), as well as type IV collagen degradation (C4G). Data were analysed using non-parametric statistics. Results At baseline, CPa9-HNE (AUCROC 0.70 0.54-0.87, p = 0.02) (fig. 1) and CPa9-HNE combined with CTX-III and PRO-C22 (AUCROC 0.75 0.60-0.89, p = 0.03), associated with CR after 1 year of VDZ therapy. OR at 1 year was associated with low levels of CTX-III (AUCROC 0.69 0.52-0.85, p = 0.03) (fig. 2), and CTX-III combined with C3M and CPa9-HNE (AUCROC 0.76 0.61-0.91, p = 0.02) at baseline. There were no associations between ECM biomarkers at VDZ baseline and clinical outcomes at 3 months. Furthermore, ECM biomarkers at time of anti-TNF discontinuation did not associate with 1-year VDZ outcomes, but CTX-III associated with CR at 3 months on VDZ (AUCROC 0.67 0.53-0.81, p = 0.02) predictive ability minimally enhanced when combining with PRO-C3 (AUCROC 0.69 0.56-0.83, p = 0.03). OR at one year also associated with CTX-III (AUCROC0.73 0.58-0.87, p = 0.003), predictive ability increasing when combining with CPa9-HNE (AUCROC 0.76 0.63-0.89, p = 0.002) Conclusion Our preliminary observations indicate that beneficial 1-year treatment outcomes on VDZ are linked to minimal inflammation and ECM turnover at VDZ baseline according to biomarkers representing reduced neutrophil activity, collagen type III degradation and collagen deposition. This calls for confirmatory studies on the clinical utility of ECM biomarkers in the choice of sequencing to VDZ. Conflict of interest: Mrs. Frimor, Camilla: Sorokina Alexdóttir, Marta: Full time employee at Nordic Bioscience Tsapanou Katranara, Thomai: Full time employee at Nordic Bioscience Satriano, Letizia: Full time employee at Nordic Bioscience Ainsworth, Mark Andrew: lectures/consulting for Abbvie, Celltrion, Eli Lilly, Janssen, MSD Mortensen, Joachim: Full time employee and shareholder at Nordic Bioscience. Steenholdt, Casper: Lectures for Takeda, MSD and Janssen-Cilag research grant from Takeda.
Frimor et al. (2026) studied this question.