title: The impact of introducing thioguanine nucleotide monitoring into an inflammatory bowel disease clinic.
abstract: BACKGROUND
  Thioguanine nucleotides (TGNs) are the active product of thiopurine metabolism. Levels have been correlated with effective clinical response. Nonetheless, the value of TGN monitoring in clinical practice is debated. We report the influence of introducing TGN monitoring into a large adult inflammatory bowel disease (IBD) clinic.
  
  
  METHODS
  Patients with IBD undergoing TGN monitoring were identified from Purine Research Laboratory records. Whole blood TGNs and methylated mercaptopurine nucleotides were hydrolysed to the base and measured using HPLC. Clinical and laboratory data were obtained retrospectively.
  
  
  RESULTS
  One hundred and eighty-nine patients with 608 available TGN results were identified. In non-responders, TGNs directed treatment change in 39/53 patients. When treatment was changed as directed by TGN, 18/20 (90%) improved vs. 7/21 (33%) where the treatment decision was not TGN-directed, p < 0.001. Where treatment change was directed at optimisation of thiopurine therapy, 14/20 achieved steroid-free remission at 6 months vs. 3/10 where the TGN was ignored, (p = 0.037). Six per cent of patients were non-adherent, 25% under-dosed and 29% over-dosed by TGN. Twelve per cent of patients predominantly methylated thiopurines, this group had low TGN levels and high risk of hepatotoxicity. In responders, adherence and dosing issues were identified and TGN-guided dose-reduction was possible without precipitating relapse. Mean cell volume (MCV), white blood cell count (WBC) and lymphocyte counts were not adequate surrogate markers. MCV/WBC ratio correlated with clinical response, but was less useful than TGN for guiding clinical decisions.
  
  
  CONCLUSIONS
  Monitoring TGNs enables thiopurine therapy to be optimised and individualised, guiding effective treatment decisions and improving clinical outcomes.
authors.affiliation: Department of Gastroenterology, St Thomas' Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Smith
authors.forename: P
authors.initials: P
authors.lastname: Blaker
authors.forename: C
authors.initials: C
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Marinaki
authors.forename: M
authors.initials: M
authors.lastname: Arenas
authors.forename: E
authors.initials: E
authors.lastname: Escuredo
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: P
authors.initials: P
authors.lastname: Irving
authors.forename: J
authors.initials: J
authors.lastname: Sanderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000008:administration & dosage*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D055118:Medication Adherence; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000627:therapeutic use; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine