P419 Concentrations of anti-TNF agents in non-inflamed intestinal tissue are associated with the long-term outcome of patients with Crohn's disease

Abstract

Background: Many reports show that high serum trough levels of anti-tumor necrosis factor (TNF) agents are required for the sustained remission in patients with Crohn's disease (CD). However, the pharmacokinetics of anti-TNF agents in intestinal mucosa was poorly investigated. The aim of our study was to investigate the correlation between the tissue concentration of anti-TNF agents and long-term disease outcome. Methods: This was a prospective single center study and 25 patients with CD administered infliximab or adalimumab as a maintenance therapy were enrolled. All participants received colonoscopy or balloon-assisted small bowel endoscopy two weeks after the administration of anti-TNF agents. Biopsy samples obtained from the inflamed and non-inflamed intestinal tissue were immersed in distilled water in the concentration of 0.1 mg/ μl. Tissue concentrations of anti-TNF agents were evaluated by enzyme-linked immunosorbent assay and the correlation with serum trough levels was compared. Moreover, we investigated the association between tissue concentrations of anti-TNF agents and the time to therapeutic interventions defined as no additional medical, endoscopic, and surgical treatment for 24 months. Results: Concentrations of anti-TNF agents in the inflamed tissue were significantly higher than that in the non-inflamed tissue (1.7 versus 1.0 μg/g, median, p=0.0011). Crohn's Disease Activity Index score and modified Rutgeerts score were not associated with the levels of anti-TNF agents in either inflamed or non-inflamed tissue. Serum trough concentrations of infliximab and adalimumab were 2.3 μg/ml (median, range [0.2–7.0]) and 10.4 μg/ml (0.8–22.8), respectively. When the patients were divided by median serum trough levels of each anti-TNF agent, patients with high serum trough concentrations of anti-TNF agents had significantly higher anti-TNF agents levels in the non-inflamed tissue than those with low serum trough concentrations (1.2 versus 0.0 μg/g, median, p=0.0346), but the difference was not observed in the inflamed tissue. Patients with high concentrations of anti-TNF agents in the non-inflamed tissue (>1.3 μg/g) had significantly longer time to therapeutic interventions than those with low concentrations of anti-TNF agents (15.5 versus 3.0 months, HR 0.33; 95% CI: 0.09–0.93). Conclusions: The concentrations of anti-TNF agents in the non-inflamed mucosa can reflect sustained remission and be a biomarker for monitoring therapeutic intensity in CD patients receiving anti-TNF agents.