Infliximab and Ustekinumab Clearance Better Predict Endoscopic Outcomes Than Trough Concentrations in Crohn's Disease.

IF 12 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Clinical Gastroenterology and Hepatology Pub Date : 2025-09-07 DOI:10.1016/j.cgh.2025.08.030

Zhigang Wang, Yannick Hoffert, Wei Zhang, Wannee Kantasiripitak, Bram Verstockt, João Sabino, Marc Ferrante, Paul Declerck, Geert D'Haens, David Laharie, Séverine Vermeire, Erwin Dreesen

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引用次数: 0

Abstract

Background & aims: Infliximab and ustekinumab clearance have been suggested as predictors of disease activity in patients with inflammatory bowel diseases. We aimed to investigate the benefits of clearance monitoring for predicting endoscopic outcomes in patients with Crohn's disease (CD).

Methods: Data from patients with moderate-to-severe CD starting infliximab (n = 108) and ustekinumab (n = 80) therapy were repurposed. Endoscopic remission (CD Endoscopic Index of Severity <3) was assessed at week (w)12 and w54 of infliximab therapy. Endoscopic response (>50% reduction in Simple Endoscopic Score for CD) was assessed at w24 of ustekinumab therapy. We performed Bayesian forecasting to estimate time-varying mAb clearance using drug concentrations, covariates, and in-house developed population pharmacokinetics models.

Results: Patients achieving endoscopic remission at w12 had significantly lower infliximab clearance and higher infliximab serum trough concentrations (C_trough) at w2 of standard 5 mg/kg infliximab induction therapy, than patients without endoscopic remission (P < .05). During infliximab maintenance therapy (with eventual dose optimizations), patients achieving endoscopic remission at w54 had significantly lower infliximab clearance (P < .001) but not higher infliximab C_trough (P = .92) than those without remission. Moreover, infliximab clearance during maintenance had similar discriminative ability as fecal calprotectin (area under the receiver operating characteristics curve 0.63; 95% confidence interval, 0.56-0.69 vs 0.67; 95% confidence interval, 0.61-0.73, respectively). Ustekinumab clearance, but not C_trough, was significantly different between endoscopic responders and nonresponders during standard ustekinumab induction and maintenance therapy (P < .05).

Conclusions: Although C_trough loses its ability to predict treatment response when doses are optimized or not administered by bodyweight, infliximab and ustekinumab clearance remains a reliable predictor for endoscopic outcomes.

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英夫利昔单抗和乌斯特金单抗清除率比克罗恩病的低谷浓度更好地预测内镜结果。

背景和目的：英夫利昔单抗和乌斯特金单抗清除率被认为是炎症性肠病患者疾病活动性的预测因子。我们的目的是研究清除率监测对预测克罗恩病（CD）患者内镜预后的益处。方法：对开始英夫利昔单抗（n=108）和ustekinumab （n=80）治疗的中重度CD患者的数据进行重新分析。在ustekinumab治疗的第24周评估内镜缓解（CD内镜严重程度指数，CD简单内镜评分降低50%）。我们使用药物浓度、协变量和内部开发的群体药代动力学模型进行贝叶斯预测，以估计随时间变化的单抗清除率。结果：在内镜下获得缓解的患者，在标准的5 mg/kg英夫利昔单抗诱导治疗中，在第12 w12时，英夫利昔单抗清除率显著低于无内镜下缓解的患者（p谷（p=0.92）），而在第2 w2时，英夫利昔单抗血清谷浓度（Ctrough）显著高于无内镜下缓解的患者。此外，维持期间英夫利昔单抗清除率与粪便钙保护蛋白具有相似的判别能力（受试者工作特征曲线下面积分别为0.63[95%置信区间0.56-0.69]和0.67[0.61-0.73]）。在标准的Ustekinumab诱导和维持治疗期间，Ustekinumab清除率在内镜应答者和无应答者之间存在显著差异(结论：当剂量优化或不按体重给药时，虽然Ctrough失去了预测治疗反应的能力，但英夫利昔单抗和Ustekinumab清除率仍然是内镜结果的可靠预测因子。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Gastroenterology and Hepatology 医学-胃肠肝病学

CiteScore

16.90

自引率

4.80%

发文量

903

审稿时长

22 days

期刊介绍： Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion. As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.