The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: The ATLAS study

Andres J. Yarur, Anjali Jain, Daniel A. Sussman, Jamie S. Barkin, Maria A. Quintero, Fred Princen, Richard Kirkland, Amar R. Deshpande, Sharat Singh, Maria T. Abreu

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Objective The aim of this study was to assess the correlation between serum and intestinal anti-tumour necrosis factor (TNF) levels, and their relationship to endoscopic disease activity and levels of TNF. Design Cross-sectional study of 30 patients receiving treatment with infliximab or adalimumab for Crohn's disease or UC. For each patient, a sample of serum was matched to tissue biopsies. Endoscopic and histological disease activity was recorded for each tissue sample. Results There was a significant positive correlation between anti-TNF in serum and tissue (r=0.3920, p=0.002), especially in uninflamed tissue (r=0.50, p<0.001), but not with those samples that had inflammation (r=0.19, p=0.54). Anti-TNF concentration in tissue correlated with degree of endoscopic inflammation, except for tissue with severe inflammation in which anti-TNF levels were again lower (mean normalised anti-TNF in tissue: uninflamed=0.93, mild=2.17, moderate=13.71, severe=2.2 inflammation (p=0.0042)). The ratio of anti-TNF-to-TNF in tissue was highest in uninflamed areas and lowest in severely inflamed areas. Patients with active mucosal disease had a higher rate of serum to tissue drug level mismatch when compared to those in remission (73.3% vs 33.3%, respectively; p=0.03). Conclusions Our data suggest that local tissue inflammation characterised by high levels of TNF serves as a sink for anti-TNF. We further postulate that some patients with high serum anti-TNF levels have active disease because tissue levels of anti-TNF are insufficient to neutralise local TNF production.

Original languageEnglish (US)
Pages (from-to)249-255
Number of pages7
JournalGut
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2016

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: The ATLAS study'. Together they form a unique fingerprint.

  • Cite this