TY - JOUR
T1 - Differential Serum-intestinal Dynamics of Infliximab and Adalimumab in Inflammatory Bowel Disease Patients
AU - Bar-Yoseph, Haggai
AU - Blatt, Alexandra
AU - Gerassy, Shiran
AU - Pressman, Sigal
AU - Mousa, Amjad
AU - Sabo, Edmond
AU - Waterman, Matti
AU - Ungar, Bella
AU - Ben-Horin, Shomron
AU - Chowers, Yehuda
N1 - Publisher Copyright:
© The Author(s) 2021.
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - Anti-TNF
KW - IBD
KW - biopsies
KW - drug levels
UR - http://www.scopus.com/inward/record.url?scp=85134429610&partnerID=8YFLogxK
U2 - 10.1093/ecco-jcc/jjab208
DO - 10.1093/ecco-jcc/jjab208
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C2 - 34849649
AN - SCOPUS:85134429610
SN - 1873-9946
VL - 16
SP - 884
EP - 892
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 6
ER -