P987 Impact of Crohn’s Disease Location on Biologic Therapy Persistence and the Risk of Intestinal Surgery: Insights from the ENEIDA Registry (the DISCOLOC Study)

Abstract

Background Crohn's disease (CD) presents differences in genetics, inflammatory components, and microbiota depending on its location. Therapy efficacy may be linked to disease location, but existing research has yielded conflicting results. This study aims to investigate the impact of CD location on first-line biologic therapy requirement and persistence and the risk of intestinal resections. Methods CD patients included in the prospectively maintained ENEIDA registry between January 2005 and May 2023 were considered for the study. Demographics, disease phenotype and location, complications, the utilization of biologic therapies, and intestinal surgeries were analyzed. Cox proportional hazards and Kaplan-Meier methods were used for the analysis of biologic requirement and persistence and risk of surgery. Results A cohort of 17,508 patients was included, with a median follow-up period of 6 years (IQR 2-10 years). The most common disease locations were ileal (43.3%) and ileocolonic (39%), with lower frequency for colonic (16.4%) and upper-gastrointestinal disease (1.2%). A first biologic was used in 54.5% of patients (n=9,543), with a higher 5-year requirement in ileocolonic disease compared to ileal and colonic disease (60.1% vs 53% vs 49.9%, p<0.001). Ileal disease presented the lowest 5-year persistence rate compared to ileocolonic and colonic location (39% vs 41.6% vs 45.1%, p=0.004). Ileal location (aHR 1.084, 95%CI 1.006-1.167), female sex (adjusted Hazard Ratio [aHR] 1.173, 95%CI 1.096-1.254), extraintestinal manifestations (aHR 1.163, 95%CI 1.080-1.251), a history of abdominal surgery (aHR 1.539, 95%CI 1.426-1.661) were independent predictors of drug discontinuation. The cumulative need for intestinal resections was 25.8% (n=4,512), with ileal disease showing the highest hazard for 5-year surgery compared to ileo-colonic and colonic location (19.5% vs 17.8 vs 8.3%, p<0.001). Ileal disease (aHR 1.194, 95%CI 1.101-1.295), stricturing (aHR 2.575, 95%CI 2.378-2.787) and penetrating phenotypes (aHR 2.485, 95%CI 2.261-2.734), a history of biologic therapy (aHR 1.386, 95%CI 1.262-1.522) and smoking (aHR 1.089, 95%CI 1.004-1.180) were independent predictors of intestinal resections. Survival analysis for biologic requirement, persistence, and the risk of intestinal resections is illustrated in Figure 1. Conclusion Ileal disease is associated with a higher requirement for biologic therapy, showing the poorest persistence. It also demonstrates the highest probability of intestinal resections among CD locations. These findings provide valuable insights into tailoring treatment strategies based on CD location.