炎症性肠病患者中英夫利昔单抗和阿达木单抗的血清-肠道动力学差异。

Differential Serum-intestinal Dynamics of Infliximab and Adalimumab in Inflammatory Bowel Disease Patients.

机构信息

Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel.

Bruce Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.

出版信息

J Crohns Colitis. 2022 Jul 14;16(6):884-892. doi: 10.1093/ecco-jcc/jjab208.

DOI:10.1093/ecco-jcc/jjab208

PMID:34849649

Abstract

BACKGROUND AND AIMS

Therapeutic drug monitoring is used to guide anti-tumour necrosis factor [TNF] therapy. However, the associations between serum drug levels [SDL], TNF-bound, and free anti-TNF in the target tissue are incompletely defined. We aimed to assess the interactions between these parameters in inflammatory bowel disease [IBD] patients.

METHODS

ENZYME-LINKED IMMUNOSORBENT: assays [ELISA assays] were used to detect free drug and TNF-drug complexes in intestinal tissues. Concurrent SDL, anti-drug antibodies [ADA], pharmacotherapy, clinical response, endoscopic appearance, and histological severity were determined. Comparisons between anti-TNFs and paired inflamed/non-inflamed tissue were performed. Variables were correlated and potential interactions detected using multivariate analysis.

RESULTS

A total of 95 biopsies taken from 49 anti-TNF treated IBD patients [26 receiving infliximab and 23 adalimumab] were studied. Free drug levels were higher in inflamed compared with non-inflamed paired specimens. Tissue free-drug and TNF-drug complexes levels were higher in adalimumab-treated patients. In adalimumab-treated patients, SDL were correlated with free drug, but not TNF-drug complex levels, in both inflamed and non-inflamed segments. In infliximab-treated patients, higher SDL were associated with the presence of tissue free drug in both inflamed and non-inflamed segments, whereas TNF-drug complexes were mostly detected in non-inflamed but not in inflamed tissue. In the presence of ADA, neither free drug nor TNF-infliximab complexes were measured in the tissue. Tissue levels did not correlate well with clinical, endoscopic, or histological scores.

CONCLUSIONS

SDL correlated with tissue free drug levels; however, different dynamics were observed for TNF-drug complex levels. Infliximab and adalimumab tissue drug dynamics differ. Better understanding of these interactions may allow future therapeutic optimisation.

摘要

背景与目的

治疗药物监测用于指导抗肿瘤坏死因子（TNF）治疗。然而，血清药物水平（SDL）、TNF 结合物和靶组织中游离抗 TNF 之间的关联尚未完全明确。本研究旨在评估炎症性肠病（IBD）患者中这些参数之间的相互关系。

方法

酶联免疫吸附测定（ELISA）用于检测肠道组织中的游离药物和 TNF-药物复合物。同时测定 SDL、抗药物抗体（ADA）、药物治疗、临床反应、内镜表现和组织学严重程度。比较了不同抗 TNF 药物与配对的炎症/非炎症组织之间的差异。采用多元分析对变量进行相关性和潜在相互作用的检测。

结果

共研究了 49 例接受抗 TNF 治疗的 IBD 患者（26 例接受英夫利昔单抗治疗，23 例接受阿达木单抗治疗）的 95 个活检标本。与配对的非炎症组织相比，炎症组织中的游离药物水平更高。与英夫利昔单抗治疗组相比，阿达木单抗治疗组的组织游离药物和 TNF-药物复合物水平更高。在阿达木单抗治疗组中，SDL 与炎症和非炎症肠段的游离药物相关，但与 TNF-药物复合物水平无关。在英夫利昔单抗治疗组中，较高的 SDL 与炎症和非炎症肠段组织中游离药物的存在相关，而 TNF-英夫利昔单抗复合物主要在非炎症组织中检测到，而不是在炎症组织中。ADA 存在时，在组织中未检测到游离药物或 TNF-英夫利昔单抗复合物。组织水平与临床、内镜或组织学评分相关性不佳。