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P268. Thiopurine metabolite measurement and the management of inflammatory bowel disease in South Australia: The first 18 months

N.A. Kennedy1, M.P. Doogue2, J.M. Andrews3, T.L. Asser4, P.A. Bampton1

1Dept of Gastroenterology, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, SA, Australia; 2Dept of Clinical Pharmacology, Flinders Medical Centre and School of Medicine, Flinders University, Adelaide, SA, Australia; 3IBD service, Royal Adelaide Hospital and Dept of Medicine, University of Adelaide, Adelaide, SA, Australia; 4University of South Australia, Adelaide, SA, Australia

Background: Studies have reported a concentration dependent relationship between thiopurine metabolites (6-thioguanine nucleotides [6TGN] and 6-methyl-mercaptopurine [6MMP]) and outcomes from the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Thiopurine metabolite testing is new to Australia and the effect of therapeutic drug monitoring of thiipurines on clinical outcomes is uncertain.

Aim: To audit the use of thiopurine testing in South Australia since its introduction in late 2008 and related clinical outcomes.

Methods: All inflammatory bowel disease (IBD) patients from the participating hospitals (FMC and RAH) and private clinics (SGS) who had had thiopurine metabolite testing were identified from the laboratory database. Medical records were examined to identify diagnosis, drug treatment, indication for testing and treatment changes after testing. Thiopurine, haematology and biochemistry data were obtained from the laboratory database.

Results: Of 151 IBD patients tested 122 had CD, 25 UC, 2 eosinophilic enteritis and 2 indeterminate colitis. Mean age was 38 years (range 15–85) and 56% were female. Testing was for lack of efficacy or flare in 79 (52%) patients, adverse effects in 18 (12%), both efficacy and adverse effects in 5 (3%) and for routine or other reasons in 55 (36%).

Where the test indication was a lack of efficacy 34 out of 79 had low 6TGN (<235 pmol/8×108 RBC). This led to dose escalation, reinforcement of compliance, or commencement of allopurinol (those with high 6MMP concentration). There was subsequent improvement in clinical response in 15 of these 34 patients. In contrast, an adequate or high 6TGN, in 23 of 45 cases, led to alternative therapy being instigated (usually biologic agents or surgery).

With regard to potential thiopurine toxicity, high 6TGN concentrations (>450 pmol/8×108 RBC) were seen in 4 of 5 patients with leucopenia, whereas high 6MMP (>5700 pmol/8×108 RBC) was seen in only 1 of 6 with abnormal LFTs.

Conclusions: Since its introduction, thiopurine metabolite testing is being used in South Australia to investigate non-responders, those with possible adverse effects and to monitor treatment in asymptomatic patients. This audit suggests thiopurine metabolites have the greatest clinical utility when used as a diagnostic test in patients with lack of efficacy or toxicity. A prospective trial of concentration-targeted dosing is needed to confirm this benefit.