P0323 Serum leucine-rich α2-glycoprotein (LRG) and Monocyte chemoattractant protein-1 (MCP-1) as Novel Biomarkers for Predicting Vedolizumab Response in Ulcerative Colitis Patients

Abstract Background Close monitoring of disease activity is essential for the therapeutic management of inflammatory bowel disease. A minimally invasive and reliable serum biomarker is desirable, but its reliability and validity have not yet been fully evaluated. The purpose of this study (UMIN000043185) was to investigate the utility of leucine-rich α-2-glycoprotein (LRG) in the management of vedolizumab therapy in patients with ulcerative colitis (UC), and to identify mucosal signatures and surrogate biomarkers by using serum cytokine and mucosal transcriptome analysis. Methods Serum LRG, C-reactive protein (CRP), serum Mucosal Vascular Addressin Cell Adhesion Molecule 1(MadCAM1), serum vedolizumab levels, 19 serum cytokines, and fecal calprotectin (fCal) were measured over 54 weeks (week 0, 2, 6, 14, 30, and 54) (n=21). Clinical remission (Mayo score <= 2, all subscore < = 1) and mucosal healing (Mayo endoscopic subscore <= 1) at week 14 were compared between the clinical remission (CR) group (n=11) and non-clinical remission (non-CR) group (n=10), and between the mucosal healing (MH) group (n=14) and non-mucosal healing (non-MH) group (n=7). Differentially expressed gene (DEG) extraction was performed by stratifying data at week 0 and comparing two groups: CR (n=10) and non-CR (n=3), and complete MH (Mayo endoscopic subscore = 0) (n=8) and non-complete MH (n=6) at week 14. Results Serum LRG concentrations were significantly lower in CR group compared to the non-CR group at week 0 (19.0 vs. 29.0 ug/mL, p=0.027) and week 6 (13.4 vs. 19.6 ug/mL, p=0.034) and significantly lower in MH group compared to the non-MH group at week 6 (13.7 vs. 21.6 ug/mL, p=0.033). In contrast, there were no significant differences in serum CRP and fecal calprotectin levels at any time point for either CR or MH. Serum MCP-1 levels showed significant differences between CR and non-CR at week 0 (609.0 vs 403.4 pg/mL, p=0.0018), between MH and non-MH at week 0 (587.2 vs 358.9 pg/mL, p<0. 001), week 6 (606.9 vs 451.6 pg/mL, p=0.015). DEGs extracted from colon tissue included LRG1 and LRG-related cytokines, MCP-1, reflecting the effect of vedolizumab treatment. Conclusion Both serum LRG (lower in CR/ MH group) and serum MCP-1 (higher in CR/MH group) were suggested to be promising predictive biomarkers of vedolizumab treatment response in patients with UC. Further studies are needed to assess their reliability and validity as indicators of treatment effectiveness.