title: The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study.
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.
  
  
  METHODS
  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.
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Andres J
authors: AJ
authors: Yarur
authors: Prometheus Laboratories, San Diego, California, USA.
authors: Anjali
authors: A
authors: Jain
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Daniel A
authors: DA
authors: Sussman
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Jamie S
authors: JS
authors: Barkin
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Maria A
authors: MA
authors: Quintero
authors: Prometheus Laboratories, San Diego, California, USA.
authors: Fred
authors: F
authors: Princen
authors: Prometheus Laboratories, San Diego, California, USA.
authors: Richard
authors: R
authors: Kirkland
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Amar R
authors: AR
authors: Deshpande
authors: Prometheus Laboratories, San Diego, California, USA.
authors: Sharat
authors: S
authors: Singh
authors: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA.
authors: Maria T
authors: MT
authors: Abreu
mesh_terms: D000068879:Adalimumab / Q000032:analysis* / Q000097:blood; D003430:Cross-Sectional Studies; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000188:drug therapy; D000069285:Infliximab / Q000032:analysis* / Q000097:blood; D007413:Intestinal Mucosa / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000097:blood
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab
keywords: CROHN'S DISEASE; INFLAMMATORY BOWEL DISEASE; INFLIXIMAB; INTESTINAL EPITHELIUM; ULCERATIVE COLITIS