title: Addition of thiopurines can recapture response in patients with Crohn's disease who have lost response to anti-tumor necrosis factor monotherapy.
abstract: OBJECTIVE
  Anti-tumor necrosis factor (TNF) antibodies are effective in maintaining remission in Crohn's disease. However, a significant proportion of patients lose response to these agents with time. This study aimed to determine whether the introduction of a thiopurine in patients who have lost response to anti-TNF monotherapy results in regained response.
  
  
  METHODS
  Five patients (four males; aged 22-38 years) with active Crohn's disease, who had an initial response to anti-TNF therapy but had lost response, were commenced on azathioprine or mercaptopurine at standard doses while continuing anti-TNF therapy. All had previously failed thiopurine therapy prior to starting anti-TNF treatment.
  
  
  RESULTS
  All patients experienced improved clinical symptoms within 2-6 months, with benefit sustained over a mean follow-up of 19 months. Two patients with an elevated C-reactive protein at the time of thiopurine addition demonstrated a fall in C-reactive protein. Colonoscopy before and after thiopurine addition in four patients showed improvement in all, with mucosal healing achieved in two. No adverse effects of treatment were noted.
  
  
  CONCLUSIONS
  Addition of a thiopurine in patients who have lost response to anti-TNF monotherapy is an effective strategy to recapture response even if the patient has previously failed thiopurine therapy. Thiopurines may reduce immunogenicity or act synergistically with anti-TNF therapy.
authors.affiliation: Department of Gastroenterology, St Vincent's Hospital, Melbourne, Victoria, Australia; Department of Gastroenterology, National University Hospital, Singapore.
authors.forename: David E H
authors.initials: DE
authors.lastname: Ong
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kamm
authors.forename: Juanda Leo
authors.initials: JL
authors.lastname: Hartono
authors.forename: Mark
authors.initials: M
authors.lastname: Lust
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D057915:Drug Substitution; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D000069285:Infliximab; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D017211:Treatment Failure; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; C488629:azathiopurine; D000069285:Infliximab; D015122:Mercaptopurine; D000068879:Adalimumab
keywords: Crohn's disease; anti-TNF; inflammatory bowel disease; loss of response; thiopurine; thiopurines