Differential serum-intestinal dynamics of infliximab and adalimumab in inflammatory bowel disease patients.

BACKGROUND AND AIMS Therapeutic drug monitoring is used to guide anti-TNF therapy. However, the association 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 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 histologic 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 Ninety-five biopsies taken from 49 anti-TNF treated IBD patients (26 infliximab and 23 adalimumab) were studied. Free drug levels were higher in inflamed compared to 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 was associated with the presence of tissue free drug in both inflamed and non-inflamed segments, while 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 histologic scores. CONCLUSION 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 optimization.