A Treatment Selection Model for Ulcerative Colitis Integrating LRG and Fuc-proHp, an IL-6-Independent Biomarker

Background: The increasing number of advanced therapy (AT) options for ulcerative colitis (UC) lacks clear selection criteria. We developed a novel fucosylated pro-Haptoglobin (Fuc-proHp) biomarker, produced in intestinal tissue, and evaluated its utility in treatment selection.
Methods: We analyzed 210 UC patients from a prospective observational study. Serum cytokines and Fuc-proHp levels were measured, and secretion patterns were assessed using principal component analyses (PCA). Fuc-proHp secretion mechanisms were investigated using a colon cancer cell line. A treatment selection model was constructed based on remission status at week 8 after AT initiation.
Results: In the PCA of biomarkers, CRP/LRG and Fuc-proHp were orthogonal on the biplot, suggesting distinct secretion mechanisms. Regression analysis of PCA data for cytokines and biomarkers indicated that IL-6 and Fuc-proHp secretion were independent processes. In Caco-2 cells, Fuc-proHp secretion was induced by IL-22 but not IL-6. Logistic regression analysis and marginal effect revealed that high Fuc-proHp levels were associated with a reduced response to anti-TNF agents but maintained responsiveness to anti-IL-23 and IL-12/23 agents. The treatment model based on LRG and Fuc-proHp achieved 78% remission in the model-matched group vs. 52% in the unmatched group.
Conclusion: The treatment selection model incorporating LRG and Fuc-proHp holds promise for advancing precision medicine in UC management.