The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study. Issue 2 (10th February 2015)

• Record Type: Journal Article
• Authors: Yarur, Andres J; Jain, Anjali; Sussman, Daniel A; Barkin, Jamie S; Quintero, Maria A; Princen, Fred; Kirkland, Richard; Deshpande, Amar R; Singh, Sharat; Abreu, Maria T
• Is Part Of: Gut. Volume 65:Issue 2(2016)
• Page Start: 249
• Page End: 255
• Publication Date: 2015-02-10
• Subjects: INFLIXIMAB -- CROHN'S DISEASE -- ULCERATIVE COLITIS -- INFLAMMATORY BOWEL DISEASE -- INTESTINAL EPITHELIUM; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2014-308099
• Languages: English
• ISSNs: 0017-5749

Abstract

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.