P367. Thiopurine metabolites measurement more effective in guiding IBD management when done during disease flare as supposed to during remission
T. Tandiari1, G. Eslick2, R. Leong1, 1Concord Repatriation General Hospital, Gastroenterology and Liver Services, Sydney, Australia, 2The Whiteley-Martin Research Centre, Gastroenterology, Sydney, Australia
In inflammatory bowel diseases, thiopurine metabolites measurement; 6-thioguanine nucleotide and 6-methyl mercaptopurine, has been proposed to explain its therapeutic failure and toxicity. The levels associated with efficacy is 235–450 pmol/8×108 for 6-TGN and hepatotoxicity for 6MMP is >5700 pmol/8×108. There is a scarcity of guidelines in terms of the timing of measurement. Thus, determining the effect of measuring thiopurine metabolites on subsequent management strategy during disease flare and remission would be useful.
Metabolites were performed on consecutive IBD patients on thiopurines and their medical records reviewed. Disease activity at the time of metabolite measurements (categorised to “flare” or “remission” based on blood tests, endoscopy and physician assessment) and any subsequent management decision (thiopurine dose increase/adjust, use of allopurinol, therapy escalation, no action) were assessed. Weight-based dosing (calculated at 1 mg/kg 6-Mercaptopurine, 2 mg/kg Azathioprine) were compared to metabolite-determined thiopurine maintenance dose.
In total, 30.9% of patients (44/142) reviewed were on thiopurines and 126 metabolites levels were measured from 2008 to 2012. Of these, 47.6% (60/126) were done during disease flare and 52.3% (66/126) during remission. Measurement of thiopurine metabolites was subsequently followed by increasing/adjusting thiopurine dose in 38% (23/60) during flare and 13.6% of tests (9/66) during remission (OR = 2.81, 95% CI: 1.13–7.42; p = 0.01). 15% (9/60) and 4.5% (3/66) of patients were identified as metabolite ‘shunters’ and started on allopurinol during flare and remission, respectively (p < 0.001). Therapy escalation (ie. biological agent, drug trial, surgery) followed metabolites measurement in 20% (12/60) during flare and 0% of tests (0/66) during remission. No action was taken after 26.6% (16/60) and 81.8% (54/66) (OR = 3.07, 95% CI: 1.53–6.34; p < 0.001) of tests when done during flare and remission, respectively. 68% (30/44) of patients were on a lesser thiopurine dose when determined by metabolites level as supposed to weight. On average, patients on 6-MP were taking 48% less (71.2% less on 6-MP/allopurinol) and patients on azathioprine 27.1% less dose (70% lower on azathioprine/allopurinol).
Metabolites measurement during IBD flare plays a useful role prior to management change. Metabolite-based thiopurine dosing may allow more patients to be on thiopurine due to potentially less toxicity risk.