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.

中文翻译：

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P987 克罗恩病位置对生物治疗持续性和肠道手术风险的影响：来自 ENEIDA 注册的见解（DISCOLOC 研究）

背景克罗恩病 (CD) 根据其部位不同，在遗传学、炎症成分和微生物群方面存在差异。治疗效果可能与疾病部位有关，但现有研究得出了相互矛盾的结果。本研究旨在探讨 CD 位置对一线生物治疗需求和持续性的影响以及肠切除的风险。方法 2005 年 1 月至 2023 年 5 月期间纳入前瞻性维护的 ENEIDA 登记的 CD 患者被考虑参加该研究。分析了人口统计学、疾病表型和部位、并发症、生物疗法的使用以及肠道手术。Cox比例风险和Kaplan-Meier方法用于分析手术的生物需求、持久性和风险。结果 纳入了 17,508 名患者的队列，中位随访期为 6 年（IQR 2-10 年）。最常见的疾病部位是回肠（43.3%）和回结肠（39%），结肠（16.4%）和上消化道疾病（1.2%）的发生率较低。54.5% 的患者 (n=9,543) 使用了第一种生物制剂，与回肠和结肠疾病相比，回结肠疾病的 5 年要求更高 (60.1% vs 53% vs 49.9%，p<0.001)。与回结肠和结肠位置相比，回肠疾病的 5 年持续率最低（39% vs 41.6% vs 45.1%，p=0.004）。回肠位置（aHR 1.084，95%CI 1.006-1.167），女性（调整后的风险比[aHR] 1.173，95%CI 1.096-1.254），肠外表现（aHR 1.163，95%CI 1.080-1.251），病史腹部手术（aHR 1.539，95%CI 1.426-1.661）是停药的独立预测因素。肠切除的累积需求为 25.8% (n=4,512)，与回结肠和结肠位置相比，回肠疾病显示 5 年手术的风险最高 (19.5% vs 17.8 vs 8.3%，p < 0.001)。回肠疾病（aHR 1.194，95%CI 1.101-1.295），狭窄（aHR 2.575，95%CI 2.378-2.787）和穿透表型（aHR 2.485，95%CI 2.261-2.734），生物治疗史（aHR 1.386， 95%CI 1.262-1.522）和吸烟（aHR 1.089，95%CI 1.004-1.180）是肠切除的独立预测因素。图 1 说明了生物制剂需求、持续性和肠切除风险的生存分析。 结论 回肠疾病与生物治疗的较高需求相关，显示出最差的持续性。它还表明 CD 位置中肠切除的可能性最高。这些发现为根据 CD 位置定制治疗策略提供了宝贵的见解。