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P339. The routine measurement of thiopurine metabolite levels results in dose optimisation in one third of IBD patients; results from a district general hospital

H. Dewhurst1, H. Johnson2, J. Begley3, S. Weaver2, S. McLaughlin2, 1Royal Bournemouth Hospital, Gastroenterology Research, Bournemouth, United Kingdom, 2Royal Bournemouth Hospital, Gastroenterology, Bournemouth, United Kingdom, 3Royal Bournemouth Hospital, Clinical Biochemistry, Bournemouth, United Kingdom

Background

Measuring azathioprine or mercaptopurine (AZA) metabolite levels 6-TGN and 6-MMPN allows identification of patients who are: 1. non compliant with their medication, 2. On a sub-optimal dose, 3. On a supra-therapeutic dose, 4. Are preferentially metabolising azathioprine to methylated metabolites (6-MMPN:6-TGN ratio >11).

Our own and others published data demonstrate that measuring metabolite levels in patients failing azathioprine therapy followed by appropriate changes in dosing and/or the addition of allopurinol (with 75% dose reduction in AZA) can result in clinical remission in the majority of patients1. We report the outcome of the routine measurement of metabolite levels in patients treated with AZA who were in a clinical remission without side effects or abnormal liver function tests (LFTs).

Methods

All patients underwent TPMT testing, azathioprine and mercaptopurine were initiated at doses of 2 mg/kg and 1 mg/kg respectively in those with wild-type TPMT with a 50% reduction in dose in TPMT heterozygotes. We searched the prospective database maintained by our biochemistry department for all patients who underwent metabolite level testing from September 2011 to November 2012, hospital case notes for these patients were reviewed.

The indications, results of testing, changes in clinical management and patient outcome were recorded.

Results

108 patients underwent metabolite testing, median length of follow-up since testing was 287.6 days (range 21–441), all were stable on AZA for >4 weeks with normal LFTs and in a clinical remission. 38 (35.2%) had UC, 66 (61.1%) CD, 52 (48.1%) were male.

17 (15.7%) patients had a sub-therapeutic 6-TGN, 10 (9.3%) supra-therapeutic 6-TGN level (>800) all of whom had dose optimisation. 6 (5.6%) patients were hypermethylators these were switched to allopurinol co-therapy with an appropriate reduction in AZA dose.

Conclusion

In the present study the routine measurement of AZA metabolites resulted in a change in clinical management in 30.6% of patients.

Whilst unproven in prospective longitudinal studies logic suggests that the routine measurement of AZA metabolites in all patients commenced on thiopurines followed by appropriate dose optimisation (with or without allopurinol co-prescription) should reduce or prevent the development of drug side effects, abnormal LFTs and bone marrow suppression and reduce the risk of disease relapse.

We recommend that AZA metabolite testing is performed in all patients 4–6 weeks after commending AZA.