P1009 Effectiveness of Ustekinumab in Crohn’s Disease Across Intestinal Locations: Spotlight on Isolated Small Intestinal Involvement

Abstract Background Small intestinal-predominant Crohn’s disease (CD) exhibits distinct therapeutic patterns, and is characterized by increased biological use and intestinal resection rates1-3. However, systematic evaluations of objective response of ustekinumab (UST), particularly related to disease location, are limited. Our aim was to compare the therapeutic efficacy of UST between small intestinal CD (SICD) and non-small intestinal CD (NSICD). Methods A prospective observational cohort study was conducted. Demographic and clinical characteristics were collected at baseline and 52-week follow-up, assessments including endoscopy, imaging, ultrasonography (US), histopathology, fecal calprotectin (FCP), C-reactive protein (CRP), and hemoglobin results. Patients with isolated ileal involvement (Montreal classification L1) were classified as having SICD, while NSICD was defined by L2 and L3. Primary outcome was objective remission, defined by meeting one of the following: (1) endoscopic remission (ER): Simple endoscopic score for CD (SES-CD) ≤2. (2) US remission: normal bowel wall thickness and absence of Doppler signals or detectable complications, or (3) radiological remission: complete resolution of inflammatory features. Secondary outcomes included (1) mucosal healing (MH): absence of ulcerations. (2) transmural healing (TH): complete healing of all intestinal wall layers, and (3) biochemical remission: fecal calprotectin (FCP)/C-reactive protein (CRP) normalization, (4) objective response: a clear improvement from baseline, and (5) endoscopic response: SES-CD ≤4. Results This study included 331 patients with CD (SICD 36.9%, NSICD 63.1%). Of these, 309 completed 52 weeks follow-up. Objective remission, MH, and TH were achieved by 32.7%, 25.6%, and 13.6% of patients, respectively. Biochemical remission occurred in 41.5% (FCP) and 35.2% (CRP). Objective and endoscopic response were observed in 70.2% and 42.1% of patients, respectively. Objective remission was achieved in 54/116 patients (46.6%) in the SICD group and 47/193 (24.4%) in the NSICD group. Regression analyses and propensity score matching showed significantly higher rates of objective remission, MH, and endoscopic response in SICD group. Conclusion Disease location influenced UST treatment outcomes, with SICD showing higher rates of objective remission, MH, and endoscopic response than NSICD. References: 1. Giordano A, Pérez-Martínez I, Gisbert JP, et al. ENEIDA project of GETECCU; ENEIDA project of GETECCU. Ileal Predominance in Crohn’s Disease Is Associated With Increased Intestinal Surgery and Biological Therapy Use, With Lower Treatment Persistence. Am J Gastroenterol. 2025 Jan 1;120(1):194-203. 2. Thia KT, Sandborn WJ, Harmsen WS, Zinsmeister AR, Loftus EV Jr. Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology. 2010 Oct;139(4):1147-55. 3. Kredel LI, Jödicke LJ, Scheffold A, et al. T-cell Composition in Ileal and Colonic Creeping Fat - Separating Ileal from Colonic Crohn’s Disease. J Crohns Colitis. 2019 Jan 1;13(1):79-91. Conflict of interest: Dr. Yu, Yue: Grants: This work was supported by the General Research Program (Natural Sciences), Department of Education of Zhejiang Province, China [Zhejiang University] (Y202454795), Qingfeng Research Funding Program, Zhejiang IBD Care Foundation (CCCF-QF-2023C33-5 and CCCF-QF-2022C59-22). Hu, Wen: No conflict of interest Li, Shuyan: No conflict of interest Hanwen, Chen: No conflict of interest Chen, Yan: No conflict of interest