P654 Advances in optimalisation of therapeutic drug monitoring using mucosal TNF expression and anti-TNF concentration in patients with inflammatory bowel disease treated with biologicals: Preliminary results from a single-centre study. (16th January 2018)

• Record Type: Journal Article
• Authors: Farkas, K; Elekes, G; Kata, D; Földesi, I; Lada, S; Ferenci, T; Madácsy, T; Rutka, M; Bálint, A; Bor, R; Fábián, A; Milassin, A; Szepes, Z; Nagy, F; Maléth, J; Molnár, T
• Is Part Of: Journal of Crohn's and colitis. Volume 12:Number 1(2018:Jan.)Supplement 1
• Page Start: S441
• Page End: S442
• Publication Date: 2018-01-16
• Subjects: Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjx180.781
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background: The introduction of anti-TNF therapy has dramatically changed the treatment of refractory inflammatory bowel disease (IBD-Crohn's disease [CD], ulcerative colitis [UC]). However, the clinical use of anti-TNF therapies is limited by loss of response posing significant challenge for clinicians. Therapeutic drug monitoring has gained increasing popularity in the management of IBD. However, relationship between clinical outcomes and serum anti-TNF levels is complex and controversial in many cases. The aim of this study is to simultaneously analyse the serum, mucosal and faecal infliximab and adalimumab levels, to determine the mucosal expression of TNF-α and to assess the relationship between the levels of anti TNF-α in the above-mentioned biological samples with endoscopic and clinical activities of IBD patients receiving anti-TNF maintenance therapy. Methods: Patients with luminal CD and UC receiving maintenance anti TNF-α therapy have been started to enrol in the study and the enrolment is still ongoing. Clinical disease activity is assessed, blood samples and faecal specimens are collected and colonoscopy with biopsy samples is performed in every patient. Biopsy samples are obtained from inflamed and uninflamed tissue from the colon. Mucosal TNF-α expression is detected by confocal microscopy after immunofluorescent staining. Serum, mucosal and faecal anti TNF-α and anti-drug antibody levels is determined by ELISA assay. Kendall-tau correlation coefficient was used to assess bivariate correlations. Results: Data of 19 patients have been analysed. Our preliminary measurements confirmed the higher number of TNF-α positive cell in the mucosal samples of active vs. inactive part of the bowel. However, no association could be detected between TNF-α-positive cell and mucosal anti TNF-α concentration. We were unable to find evidence against the hypothesis of no association between serum drug levels and mucosal anti TNF-α concentration, between serum drug levels and clinical or endoscopic response to anti-TNF therapy. Conclusions: Our study would be the first that simultaneously examine serum, tissue and faecal concentrations of anti TNF-α comparing with clinical and endoscopic activities. Monitoring of serum drug levels is a widely accepted approach during biological therapy. However, the sample size is currently very low, and more data are needed to be collected in order to better investigate the association between serum and tissue drug levels or disease activity. Nevertheless, it is hoped that these measurements will allow a better overview of the drug distribution and clearance and may help to identify a useful surrogate marker of clinical and endoscopic activity.