Thiopurine metabolite testing in inflammatory bowel disease.
BACKGROUND
Thiopurine use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose, and metabolite levels in a real world setting.


METHODS
Patients identified from pathology databases (2007-2012) at two tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review.


RESULTS
A total of 169 patients were included. 6-Thioguanine (TGN) levels were sub-therapeutic in 52%, therapeutic in 34%, and supratherapeutic in 14%. Test indication was active disease (79%), adverse effect (11%), or adherence assessment (7%). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) versus 447 (+/- 117.7) pmol/8 × 10(8) RBC, P = 0.05). Weight-based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5% vs standard dose 35.4%), but was significantly associated with shunting toward 6-MMP (23.1% vs 6.8%, P = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86% of patients with active disease and subtherapeutic levels and in 68% of tested patients overall.


CONCLUSIONS
Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight-based dosing did not increase rates of therapeutic levels but was associated with increased 6MMP shunting.
Monash Health, Melbourne, Victoria, Australia.|St Vincent's Hospital, Melbourne, Victoria, Australia.
Rimma
R
Goldberg
Monash Health, Melbourne, Victoria, Australia.|Centre for Inflammatory Diseases, Southern Clinical School, Monash University, Melbourne, Victoria, Australia.
Gregory
G
Moore
St Vincent's Hospital, Melbourne, Victoria, Australia.
Georgina
G
Cunningham
St Vincent's Hospital, Melbourne, Victoria, Australia.
Julien
J
Schulberg
Monash Health, Melbourne, Victoria, Australia.
Philip
P
Marsh
St Vincent's Hospital, Melbourne, Victoria, Australia.
Steven
S
Brown
St Vincent's Hospital, Melbourne, Victoria, Australia.
William
W
Connell
St Vincent's Hospital, Melbourne, Victoria, Australia.
Mark
M
Lust
St Vincent's Hospital, Melbourne, Victoria, Australia.|University of Melbourne, Melbourne, Victoria, Australia.|Imperial College, London, UK.
Michael A
MA
Kamm
St Vincent's Hospital, Melbourne, Victoria, Australia.
Sally
S
Bell
D001379:Azathioprine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D015331:Cohort Studies; D016903:Drug Monitoring; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D015122:Mercaptopurine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D012189:Retrospective Studies; D013866:Thioguanine / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D016896:Treatment Outcome
D015122:Mercaptopurine; D013866:Thioguanine; D001379:Azathioprine
IBD; metabolite testing; thiopurines