The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease

Scand J Gastroenterol. 2012 Oct;47(10):1200-10. doi: 10.3109/00365521.2012.711853. Epub 2012 Aug 6.

Abstract

Objective: To investigate the effects of adalimumab on the induction of complete endoscopic healing and normalization of mucosal cytokine gene expression in patients with active Crohn's disease.

Material and methods: A prospective, single-center study including 77 patients. All were examined by endoscopy before initiation of adalimumab induction therapy with a minimum of six adalimumab injections. Patients were treated until documentation of complete endoscopic healing. Biopsies for measurements of mRNA expression levels of interleukin(IL)-17A (IL17A), IL23, interferon-gamma (IFNG), tumor necrosis factor-alpha (TNF), IL10 and Forkhead Box P3 (FOXP3), as well as for immunohistochemistry (IHC) were sampled at pre- and post-treatment endoscopy, and from 17 control patients.

Results: Complete endoscopic healing was achieved in 27.3% after 10 weeks of treatment, documented by endoscopy at week 12. Cumulative endoscopic healing after 52 weeks was 44.2%. Complete endoscopic healing led to a significant reduction in mRNA expression levels for all cytokines except IL10. Elevated expression of TNF and IL-17A persisted in 52% and 76%, respectively, of patients with complete endoscopic remission. Pre-treatment cytokine gene expression levels did not predict response to adalimumab therapy.

Conclusions: Adalimumab induces accumulated complete endoscopic healing in 44% of patients after 52 weeks of therapy. Normalization of mucosal gene expression of cytokines does not occur in all patients with endoscopy-verified healed mucosa. Inclusion of normalized mucosal cytokine expression into the concept of mucosal healing could have an impact on long-term clinical outcome.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Biopsy
  • Crohn Disease* / diagnosis
  • Crohn Disease* / drug therapy
  • Crohn Disease* / metabolism
  • Cytokines* / genetics
  • Cytokines* / metabolism
  • Drug Monitoring / methods
  • Endoscopy, Digestive System / methods*
  • Endpoint Determination / methods
  • Female
  • Gene Expression Profiling
  • Genome-Wide Association Study
  • Humans
  • Immunohistochemistry / methods
  • Injections, Subcutaneous
  • Intestinal Mucosa* / drug effects
  • Intestinal Mucosa* / metabolism
  • Intestinal Mucosa* / pathology
  • Male
  • Real-Time Polymerase Chain Reaction
  • Remission Induction / methods
  • Treatment Outcome
  • Ulcer / diagnosis
  • Ulcer / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Adalimumab