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

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.

• Authors: Haggai Bar-Yoseph, Alexandra Blatt, Shiran Gerassy, Sigal Pressman, Amjad Mousa, Edmond Sabo, Matti Waterman, Bella Ungar, Shomron Ben-Horin, Yehuda Chowers
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 16 Issue 6 Pg. 884-892 (Jul 14 2022) ISSN: 1876-4479 [Electronic] England
• PMID: 34849649 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies
• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha
• Infliximab
• Adalimumab

Topics

• Adalimumab
• Antibodies
• Humans
• Inflammatory Bowel Diseases
• Infliximab
• Tumor Necrosis Factor Inhibitors (therapeutic use)
• Tumor Necrosis Factor-alpha