Background It is unclear whether ustekinumab (UST) concentrations can predict the clinical course of inflammatory bowel disease (IBD) and guide treatment algorithms during the induction phase. The aim of our study was to assess the association between serum UST concentrations during the induction phase and clinical outcomes at week 24 and to determine the validity of a UST threshold for guiding intensification strategies. Methods We conducted a retrospective study including Crohn's disease (CD) and ulcerative colitis (UC) patients who started UST treatment between June 2022 and February 2023. Intensification strategies were determined according to standard clinical practice. UST concentrations were collected at weeks 8, 16, and 24. Quartile analysis and logistic regression were performed to evaluate the association between UST concentrations and treatment targets. Definitions are clinical steroid-free remission as a Harvey-Bradshaw index <5 and a partial Mayo score <2; endoscopic remission as a simple endoscopic score (SES-CD) ≤2 and Mayo endoscopic score (EMS) ≤1; and endoscopic response as a ≥50% reduction in SES-CD and ≥1 point in EMS. Results We included 42 patients (CD: 24). At week 24, clinical remission rates of 67% and endoscopic response and remission rates of 57% and 28%, respectively, were achieved. At week 24, the majority of patients continued intensified treatment: 90 mg subcutaneously every 4 weeks in 55% and 130 mg intravenously every 4 weeks in 36%. Patients who achieved an endoscopic response at week 24 had higher UST levels at week 8 (4.1 vs. 2.9 µg/ml, p=0.029). No significant differences between endoscopic remission rates and UST levels at any week were observed. The differences observed in the quartile analysis between the UST concentrations at week 8 and the endoscopic response were not statistically significant (p=0.451). The area under the ROC curve value for UST levels at week 8 to predict endoscopic response was 0.734 (p=0.012). Logistic regression analysis identified prior exposure to vedolizumab and absence of perianal disease as predictors of endoscopic response and remission at week 24 in univariate analysis, but not in multivariate analysis. No association was observed between UST levels and drug persistence rates. Conclusion In this real-world cohort, higher UST concentrations at week 8 were associated with higher rates of endoscopic response at week 24. A reliable concentration threshold for predicting endoscopic response and treatment intensification could not be determined, probably due to the insufficient number of patients included in the study and the relatively poor performance of the ROC curve. Prospective, randomized studies are needed to validate these results.

中文翻译：

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P886 诱导时乌司奴单抗浓度与炎症性肠病患者的中期内镜结果相关

背景 目前尚不清楚乌特克单抗 (UST) 浓度是否可以预测炎症性肠病 (IBD) 的临床病程并指导诱导阶段的治疗方案。我们研究的目的是评估诱导期血清 UST 浓度与第 24 周临床结果之间的关联，并确定指导强化策略的 UST 阈值的有效性。方法我们对2022年6月至2023年2月期间开始UST治疗的克罗恩病（CD）和溃疡性结肠炎（UC）患者进行了回顾性研究。根据标准临床实践确定强化策略。在第 8、16 和 24 周收集 UST 浓度。进行四分位数分析和逻辑回归以评估 UST 浓度与治疗目标之间的关联。定义为临床无类固醇缓解，Harvey-Bradshaw 指数＜5，部分 Mayo 评分＜2；内镜缓解为简单内镜评分（SES-CD）≤2且Mayo内镜评分（EMS）≤1；内镜反应为 SES-CD 降低≥50%，EMS 降低≥1 分。结果 我们纳入了 42 名患者 (CD: 24)。第 24 周时，临床缓解率达到 67%，内镜缓解率和缓解率分别达到 57% 和 28%。第 24 周时，大多数患者继续强化治疗：55% 的患者每 4 周皮下注射 90 mg，36% 的患者每 4 周静脉注射 130 mg。在第 24 周达到内镜缓解的患者在第 8 周时 UST 水平较高（4.1 vs. 2.9 µg/ml，p=0.029）。任何一周内镜缓解率和 UST 水平之间均未观察到显着差异。在第 8 周时 UST 浓度与内窥镜反应之间的四分位分析中观察到的差异不具有统计学显着性 (p=0.451)。第 8 周 UST 水平预测内镜反应的 ROC 曲线下面积值为 0.734 (p=0.012)。在单变量分析中，Logistic 回归分析将先前接触维多珠单抗和不存在肛周疾病确定为第 24 周内镜反应和缓解的预测因子，但在多变量分析中则不然。未观察到 UST 水平与药物持续率之间存在关联。结论 在这个真实世界队列中，第 8 周时较高的 UST 浓度与第 24 周时较高的内镜反应率相关。无法确定预测内镜反应和治疗强化的可靠浓度阈值，可能是由于患者数量不足纳入研究的ROC曲线表现相对较差。需要进行前瞻性随机研究来验证这些结果。