P154 Evaluation of serum protein FingerPrint biomarkers of collagen, citrullinated vimentin and calprotectin in patients with inflammatory bowel disease

Luo, Y.(1);Saini, J.(2);Mortensen , J.(3);Bay-Jensen, A.(4);Karsdal, M.(5);Greenawalt, D.(2);Harris, S.(6);

(1)Bristol Myers Squibb, Translational Medicine, Lawrenceville, United States;(2)Bristol Myers Squibb, Predictive Science, Lawrenceville, United States;(3)Nordic Bioscience, Immunology, Herlev, Denmark;(4)Nordic Bioscience, Immunology, Hrelev, Denmark;(5)Nordic Bioscience, Immunology and Fibrosis, Herlev, Denmark;(6)Bristol Myers Squibb, Translational Medicine, San Diego, United States;


Inflammatory bowel disease (IBD) is characterized by chronic inflammation leading to extracellular matrix remodeling, reactive stroma and activated inflammatory cells. In the pursuit of non-invasive biomarkers of disease severity and treatment response for IBD, we evaluated Protein FingerPrint Assay (PFA) of collagen formation and degradation (PRO-C3, C3M, PRO-C4, C4M), neutrophil elastase cleaved calprotectin (CPa9-HNE) and citrullinated vimentin degradation (VICM) in serum collected from 2 clinical trials in Ulcerative Colitis (UC) and Crohns Disease (CD) (NCT01466374 and NCT01294410) and matched healthy volunteers (NHV).


PFA were generated from serum of 88 UC, 120 CD at baseline and at Day 78 of treatment and 78 NHV. Clinical remission in UC was defined as Mayo score 2 with no individual subscore >1. Clinical response as reduction from baseline in Mayo score 3 and 30%, and decrease from baseline in rectal bleeding subscore 1 or absolute rectal bleeding subscore 1. Clinical remission in CD was defined by an absolute CD Activity Index [CDAI] score < 150 and clinical response as a reduction in CDAI100 points from baseline or an absolute CDAI score < 150. Endoscopic remission was defined as SES-CD of 0. Statistical analysis was performed on all markers between diseased and NHV, pooled responders/remitters vs non-response independent of treatment arm and longitudinally.


At baseline, C3M, C4M and PRO-C4 had significantly higher median levels in UC and CD patients than NHVs. CPa9-HNE and VICM were significantly higher in CD compared to NHV, an increase in these markers was observed but did not meet significance in UC patients (Figure 1). Decrease of VICM from baseline at Day 78 were associated with remission (median -55%, p<0.05) in UC, while VICM decrease from baseline (median -56%, p<0.05) at Day 78 was associated with CD patients achieving endoscopic remission. In CD C3M and C4M was present at lower levels at baseline and during study in patients with clinical remission compared with those without remission. SES-CD scores were positively correlated with C4M, C3M, CPa9-HNE and PRO-C4 at both baseline and Day 78. CD patients achieving endoscopic remission had lower levels of C3M, C4M, PRO-C4 and CPa9-HNE at both baseline and Day 78.


C4M, C3M, PRO-C4, CPa9-HNE and VICM were found at higher levels in serum of IBD patients. VICM demonstrated potential as a biomarker for monitoring disease activity changes. Association of C4M, C3M and PRO-C4 with endoscopic remission in CD patients suggest that these markers may predict disease progress or regression in CD patients. However, further studies are warranted to evaluate these biomarkers in IBD patients.