Serum leucine-rich α-2-glycoprotein and monocyte chemoattractant protein-1 as novel biomarkers for predicting vedolizumab response in patients with ulcerative colitis

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Abstract Background and Aims Effective, minimally invasive biomarkers are needed to predict treatment outcomes in ulcerative colitis (UC). This multicenter observational study investigated predictive serum and genetic biomarkers for vedolizumab (VDZ) therapy in UC, including serum leucine-rich α-2-glycoprotein (LRG), cytokines, and differentially expressed genes (DEGs) in intestinal tissue. Methods Eligible patients (18-80 years; moderately to severely active UC) received intravenous VDZ (300 mg; Weeks 0, 2, 6, then every 8 weeks through Week 54). Serum biomarkers were compared between those who did/did not achieve clinical remission (CR; full Mayo score ≤2, all subscores ≤1) or mucosal healing (MH; Mayo endoscopic subscore ≤1) at Week 14. Week 0 inflammatory tissue data were stratified by Week 14 VDZ effect (CR and complete-MH [Mayo endoscopic subscore = 0]) for DEGs. Results Overall, 21 patients were included. Mean serum LRG was significantly lower in the CR (n = 11) versus non-CR (n = 10) group at Week 0 (19.0 vs 29.0 µg/mL; P = .0267) and Week 6 (13.4 vs 19.6 µg/mL; P = .0340), and in the MH (n = 14) versus non-MH (n = 7) group at Week 6 (13.7 vs 21.6 µg/mL; P = .0326). Mean monocyte chemoattractant protein-1 (MCP-1) was significantly different between CR and non-CR groups at Week 0 (609.0 vs 403.4 pg/mL; P = .0018) and MH versus non-MH at Week 0 (587.2 vs 358.9 pg/mL; P < .001) and Week 6 (606.9 vs 451.6 pg/mL; P = .037). No significant differences in C-reactive protein and fecal calprotectin levels were observed. DEGs included LRG1, LRG-related cytokines, and MCP1. Conclusions Serum LRG and MCP-1 may be candidate biomarkers of VDZ treatment response in UC.

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