title: The effect of adalimumab for induction of endoscopic healing and normalization of mucosal cytokine gene expression in Crohn's disease.
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.
  
  
  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.
authors.affiliation: Institute of Clinical Medicine, Research group of Gastroenterology and Nutrition, University of Tromsø, Tromsø, Norway. renathe.rismo@unn.no
authors.forename: Renathe
authors.initials: R
authors.lastname: Rismo
authors.forename: Trine
authors.initials: T
authors.lastname: Olsen
authors.forename: Guanglin
authors.initials: G
authors.lastname: Ciu
authors.forename: Eyvind J
authors.initials: EJ
authors.lastname: Paulssen
authors.forename: Ingrid
authors.initials: I
authors.lastname: Christiansen
authors.forename: Jon
authors.initials: J
authors.lastname: Florholmen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Goll
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D001706:Biopsy; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D016903:Drug Monitoring / Q000379:methods; D016145:Endoscopy, Digestive System / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome; D014456:Ulcer / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D000068879:Adalimumab