title: Thiopurine metabolite measurement leads to changes in management of inflammatory bowel disease.
abstract: BACKGROUND
  The thiopurines azathioprine and 6-mercaptopurine are recommended for maintenance of remission in inflammatory bowel disease (IBD). Measurement of concentrations of the metabolites 6-thioguanine nucleotide and 6-methylmercaptopurine helps delineate interindividual variation in metabolism that may underlie variability in efficacy and toxicity.
  
  
  OBJECTIVE
  We aimed to perform a retrospective observational study to determine the utility of thiopurine metabolite testing following its introduction into South Australia.
  
  
  METHODS
  All patients having thiopurine metabolite tests done at Flinders Medical Centre between November 2008 and January 2010 were identified. Case notes of patients with testing done in the context of treatment for IBD were interrogated to determine the reason for testing, clinical context and outcome.
  
  
  RESULTS
  One hundred and fifty-one patients were identified with thiopurine metabolite testing for IBD with 157 testing episodes. Eighty (51.0%) had testing done for flare or inefficacy, 18 (11.5%) for adverse effects, 5 (3.2%) for a combination of inefficacy and adverse effects, and 54 (34.4%) for routine or other reasons. Testing was followed by improved outcomes of increased efficacy, reduced toxicity or change to alternative therapy in 55.0% of the inefficacy/flare group, 27.8% of the suspected adverse reaction group, 60.0% of the combination group, and 13.0% of the routine/other group. Allopurinol was used as cotherapy in 16 patients and led to marked improvements in metabolite concentrations.
  
  
  CONCLUSIONS
  Thiopurine metabolite testing has quickly become established in South Australia. When used for inefficacy or adverse effects, it often leads to improved outcomes. Prospective studies are needed to determine whether routine testing to guide dosing is of benefit.
authors.affiliation: Gastrointestinal Unit, Centre for Molecular Medicine, MRC IGMM, Western General Hospital, University of Edinburgh, Edinburgh, UK. nick.kennedy@ed.ac.uk
authors.forename: N A
authors.initials: NA
authors.lastname: Kennedy
authors.forename: T L
authors.initials: TL
authors.lastname: Asser
authors.forename: R E
authors.initials: RE
authors.lastname: Mountifield
authors.forename: M P
authors.initials: MP
authors.lastname: Doogue
authors.forename: J M
authors.initials: JM
authors.lastname: Andrews
authors.forename: P A
authors.initials: PA
authors.lastname: Bampton
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D019468:Disease Management; D005260:Female; D006150:Guanine Nucleotides / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000175:diagnosis / Q000378:metabolism* / Q000628:therapy*; D008297:Male; D015122:Mercaptopurine / Q000031:analogs & derivatives* / Q000378:metabolism; D008875:Middle Aged; D012189:Retrospective Studies; D013873:Thionucleotides / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D006150:Guanine Nucleotides; D013873:Thionucleotides; C003964:6-thioguanylic acid; C010240:6-methylthiopurine; D015122:Mercaptopurine