PTH-091 Clinical outcomes of a personalised approach to the management of thiopurine drug therapy

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Abstract

Introduction

A significant number of patients with inflammatory bowel disease (IBD) are treated with thiopurine drugs. Typically target doses for Azathioprine (AZA) and 6-Mercaptopurine (6-MP) are 2.5 mg/kg and 1.25 mg/kg, respectively, provided these are tolerated. More personalised dosing can be achieved using thiopurine metabolites (TPM) assessments for 6-Thioguanine nucleotide (6-TGN) and 6-Methylmercaptopurine nucleotide (6-MMPN); improving therapeutic efficacy, whilst minimising unwanted side effects and identifying non-compliance. We were keen to assess whether the use of TPM assessments and standardised management guidelines could affect clinical outcomes.

Method

We reviewed our local patients (3462) on the National IBD Registry and identified 406 as being on TPMs. These patients were all offered TPM assessments, which 200 initially completed. Following a locally derived management algorithm, their management was standardised depending on their TPM results. This led to a change in management in 124 patients (62%). Using faecal calprotectin + CRP/ESR as objective markers of disease activity, and the HBI + mUCDAI as clinical outcome measures, we reviewed these patients before and after their TPM driven management changes. ALT, Amylase and neutrophil count were used as physiological markers to exclude thiopurine toxicity.

Results

Of the 124 whose management changed, drug doses were increased in 28, reduced in 73, stopped in 22 who were thought to be non-compliant in taking their medication, and 1 was changed from Azathioprine to 6-MP. Results from before and after the use of the thiopurine management algorithm were compared where available. Calprotectin was available for 55% of patients and showed an average decrease of 167 ug/g, with 47% decreasing and 32% increasing (by more than 38 ug/g), whilst 21% stayed the same. Improvements in ESR were not as impressive (average decrease of 0.45 mm/hr). The average HBI score decreased from 2.2 to 1.9, whilst the mUCDAI score dropped from 2.0 to 1.5. Classification of disease activity improved in 32%, stayed the same for 45% and deteriorated in 23%. Eight patients had raised ALTs, 3 had raised Amylase, and no patients suffered clinically significant neutropenia.

Conclusion

Personalising thiopurine management through TPM assessments and using a standardised management protocol enabled avoidance of any major complications. It didn’t, however,prevent minor fluctuations in ALT or amylase levels (11 patients - 9%). By optimising their dosage into appropriate therapeutic ranges, whilst avoiding toxic levels of 6-MMPN, a majority of patients saw an improvement in both their clinical disease activity scores and their objective markers of inflammation, with an average calprotectin reduction of 167 ug/g.

Disclosure of Interest

None Declared

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