title: A trial of mercaptopurine is a safe strategy in patients with inflammatory bowel disease intolerant to azathioprine: an observational study, systematic review and meta-analysis.
abstract: BACKGROUND
  Thiopurines maintain remission and modify disease course in inflammatory bowel disease. Use is limited by intolerance and subsequent drug withdrawal in approximately 17% of patients treated with azathioprine. Previous case series have addressed the success rates of re-treatment with mercaptopurine in these individuals.
  
  
  OBJECTIVE
  To determine the rate of tolerance when trialling mercaptopurine in azathioprine-intolerant patients and the factors predictive of success, and to perform a systematic review and meta-analysis of these data with other published data sets.
  
  
  METHODS
  A retrospective observational study of 149 patients with IBD (82 with Crohn's disease and 67 with ulcerative colitis) previously intolerant of azathioprine subsequently treated with mercaptopurine was performed. A meta-analysis was undertaken of all published studies of mercaptopurine use in azathioprine-intolerant patients (455 patients in 11 included studies).
  
  
  RESULTS
  Mercaptopurine was tolerated by 58% of azathioprine-intolerant patients in the Edinburgh cohort. In the meta-analysis, 68% tolerated mercaptopurine. A higher proportion of those in the meta-analysis with GI toxicity (62%) or hepatotoxicity (81%) were able to tolerate mercaptopurine than those with flu-like illness (36%). Among those patients who ceased mercaptopurine for further adverse effects, 59% experienced the same adverse effect as they had with azathioprine.
  
  
  CONCLUSIONS
  This meta-analysis shows that switching to mercaptopurine is a safe therapeutic strategy for over two-thirds of azathioprine-intolerant patients and may help optimise immunomodulatory therapy in inflammatory bowel disease. A trial of mercaptopurine should be attempted in IBD patients (except those with acute pancreatitis or bone marrow aplasia) before considering thiopurine intolerance.
authors.affiliation: Gastrointestinal Unit, Western General Hospital, Edinburgh, UK; Gastrointestinal research, Centre for molecular medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK.
authors.forename: N A
authors.initials: NA
authors.lastname: Kennedy
authors.forename: E
authors.initials: E
authors.lastname: Rhatigan
authors.forename: I D R
authors.initials: ID
authors.lastname: Arnott
authors.forename: C L
authors.initials: CL
authors.lastname: Noble
authors.forename: A G
authors.initials: AG
authors.lastname: Shand
authors.forename: J
authors.initials: J
authors.lastname: Satsangi
authors.forename: C W
authors.initials: CW
authors.lastname: Lees
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000188:drug therapy*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine