Tsuyoshi Terashima

Background: The growing number of ulcerative colitis (UC) treatments has complicated the selection process. We hypothesized that the degree of epithelial neutrophilic infiltration, which is a hallmark of interleukin-23 (IL-23) pathway activation, could guide personalized therapy. Methods: This single-center, prospective study included 42 patients with active UC who were treated between July 2024 and September 2025. The study was registered (NCT 06626165) on 20 July 2024. Prior to treatment, all patients underwent colonoscopy with biopsy. Using a refined subclassification of the Geboes histopathology score, patients were stratified into two groups based on the percentage of crypts with neutrophilic infiltration: Grade ≥ 3.2 and Grade < 3.2. The primary outcome was clinical remission at four weeks. The secondary outcome was endoscopic remission at six months. Results: Of the 42 patients, 22 were classified as Grade ≥ 3.2, and 20 were classified as Grade < 3.2. Baseline clinical and endoscopic characteristics were similar between the two groups. All 22 patients in the Grade ≥ 3.2 group treated with mirikizumab achieved clinical remission within four weeks. Nineteen (86%) of the twenty-two patients achieved endoscopic remission within six months. All 20 patients in the Grade < 3.2 group who received vedolizumab (16) or upadacitinib (4) achieved clinical remission within the same timeframe. Both treatment strategies led to a statistically significant reduction in the inflammatory biomarker leucine-rich alpha-2-glycoprotein (LRG) (p < 0.001). Conclusions: Our findings suggest that UC patients with advanced epithelial neutrophil infiltration (Geboes Grade ≥ 3.2) may have a disease that is predominantly driven by the IL-23 pathway, making them potential candidates for selective IL-23p19 inhibitors. This histopathology-driven approach appears to be a useful strategy for tailoring treatment to patients with active UC, though further validation is required.

Background: Interleukin (IL)-23 exerts its effects by activating Th17 cells, resulting in high neutrophilic infiltration in the colonic mucosal epithelium. We have developed a scoring method for refining the Geboes score Grade 3 to identify active ulcerative colitis (UC) patients with high epithelial neutrophilic infiltration (Geboes Grade 3.2 or 3.3). Methods: Colonoscopy and histology findings were assessed using the Mayo endoscopic subscore (MES) and the Geboes score Grade 3. The percentage of crypts with neutrophilic infiltration, which was calculated as the number of crypts with neutrophilic infiltration/total crypts in a glass slide, was used to subclassify the Geboes score Grade 3 into Grades 3.0, 3.1, 3.2, and 3.3. Results: This scoring method was then applied to 30 enrolled patients (20 men; median age: 46 years), yielding the following distribution: Geboes Grade 3.0 in six (20%) patients, Grade 3.1 in seven (23%) patients, Grade 3.2 in sixteen (53%) patients, and Grade 3.3 in one (3%) patient. Of the 18 UC patients with MES 2, 5 (28%) were classified as Grade 3.1 and 12 (67%) were classified as Grade 3.2. One of the IL-23 antagonists, mirikizumab treatment, resulted in clinical and endoscopic improvements in 10 active UC patients who were classified as Geboes score ≥ 3.2. Conclusions: We developed a novel Geboes score Grade 3 scoring method and applied it to 30 patients; approximately 60% were classified as Grade 3.2 or higher. This method may help to identify UC patients who are likely to respond effectively to IL-23 antagonists.