Liefferinckx Claire, Hubert Antoine, Thomas Debby, Bottieau Jérémie, Minsart Charlotte, Cremer Anneline, Amininejad Leila, Vallée François, Toubeau Jean-François, Franchimont Denis
Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Route de Lennik 808, Brussels 1070, Belgium; Department of Gastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Department of Electrical Engineering, University of Mons, Mons, Belgium.
Dig Liver Dis. 2023 Mar;55(3):366-372. doi: 10.1016/j.dld.2022.07.015. Epub 2022 Aug 14.
Despite the therapeutic efficacy of Ustekinumab (UST) in Crohn's disease (CD), loss of response (LOR) is observed over time. This study aims to evaluate the impact of the UST pharmacokinetics (PK) at induction on clinical and endoscopic outcomes, as well as to find predictive markers of UST response.
This retrospective study included 80 CD patients. Pharmacokinetics data (trough levels (TLs)) combined with clinical and biological parameters were fed into tailored logistic regression and tree-based ensemble techniques to predict clinical and endoscopic outcomes at one year of follow-up.
TLs at week 16 were significantly lower among patients with moderate to severe endoscopic activity during the follow-up (p = 0.04). The best model to predict endoscopic outcome was obtained at week 16 by Random Forest with an area under the receiver operating characteristic curve of 0.92 ± 0.08, sensitivity 91% and specificity 75%, with key inputs such as lymphocyte and monocyte counts at week 8, and UST TLs and CRP at week 16.
This real-world study confirms the relationship between early UST TLs and both clinical and endoscopic outcomes. Models were developed for the task of predicting clinical and endoscopic remission in CD patients treated with UST, highlighting the clinical relevance of UST TLs at week 16.
尽管乌司奴单抗（UST）在克罗恩病（CD）治疗中具有疗效，但随着时间推移会出现反应丧失（LOR）。本研究旨在评估诱导期UST药代动力学（PK）对临床和内镜结果的影响，并寻找UST反应的预测标志物。
这项回顾性研究纳入了80例CD患者。将药代动力学数据（谷浓度（TLs））与临床和生物学参数相结合，输入定制的逻辑回归和基于树的集成技术，以预测随访一年时的临床和内镜结果。
随访期间中度至重度内镜活动患者在第16周时的TLs显著较低（p = 0.04）。预测内镜结果的最佳模型在第16周时通过随机森林获得，受试者操作特征曲线下面积为0.92±0.08，敏感性为91%，特异性为75%，关键输入参数包括第8周时的淋巴细胞和单核细胞计数，以及第16周时的UST TLs和CRP。
这项真实世界研究证实了早期UST TLs与临床和内镜结果之间的关系。开发了用于预测接受UST治疗的CD患者临床和内镜缓解情况的模型，突出了第16周时UST TLs的临床相关性。
