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Original article
The association of tissue anti-TNF drug levels with serological and endoscopic disease activity in inflammatory bowel disease: the ATLAS study
  1. Andres J Yarur1,
  2. Anjali Jain2,
  3. Daniel A Sussman1,
  4. Jamie S Barkin1,
  5. Maria A Quintero1,
  6. Fred Princen2,
  7. Richard Kirkland2,
  8. Amar R Deshpande1,
  9. Sharat Singh2,
  10. Maria T Abreu1
  1. 1Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida, USA
  2. 2Prometheus Laboratories, San Diego, California, USA
  1. Correspondence to Dr Maria T Abreu, Division of Gastroenterology, Department of Medicine, University of Miami Miller School of Medicine, Gautier, 510 (D-149), 1011 NW 15th Street, Miami, FL 33136, USA; mabreu1{at}med.miami.edu

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.

  • INFLIXIMAB
  • CROHN'S DISEASE
  • ULCERATIVE COLITIS
  • INFLAMMATORY BOWEL DISEASE
  • INTESTINAL EPITHELIUM

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