Abstract
INTRODUCTION: Eosinophils may contribute to ulcerative colitis (UC) pathogenesis through inflammation and epithelial injury. Mirikizumab, a selective IL-23 inhibitor, has shown efficacy in moderate-to-severe UC. However, the relationship between eosinophils and treatment outcomes with IL-23 inhibition remains unclear. OBJECTIVE: This post-hoc analysis of the LUCENT-1 trial evaluated trends in serum and histologic eosinophils as biomarkers for early response to mirikizumab induction therapy in UC. DESIGN: Data from LUCENT-1 (NCT03518086) were analyzed to assess serum eosinophil counts and histologic eosinophil presence at baseline and week 12. Clinical response, remission, and endoscopic improvement were defined by modified Mayo score criteria. Logistic regression models, adjusted for factors including steroid use, prior biologic failure, disease severity, and albumin levels, assessed associations between baseline eosinophil levels and treatment outcomes. RESULTS: Among 928 participants, 66.6% achieved clinical response. Responders had higher baseline serum eosinophils (0.23 × 109/L vs 0.19 × 109/L, P = .001) and showed greater reductions at week 12. Elevated baseline eosinophils (≥0.57 × 109/L) were associated with higher rates of clinical response (80% vs 65.7%, aOR: 2.31, P = .013), remission (33.3% vs 25.1%, aOR: 1.91, P = .044), and endoscopic improvement (46.7% vs 33.8%, aOR: 2.33, P = .003). Reductions in histologic eosinophils were also linked to improved outcomes, especially in those with moderate/marked baseline presence. CONCLUSIONS AND RELEVANCE: Baseline eosinophil levels may predict response to mirikizumab and guide early treatment decisions. These findings support a potential role for eosinophils as biomarkers in UC management.