PWE-088 The Impact Of Thiopurine Hypermethylation On Clinical Outcomes In Patients With Ibd

Introduction 15% of patients with inflammatory bowel disease (IBD) prescribed azathioprine (AZA)/mercaptopurine (MP) demonstrate a skewed drug metabolism with low thioguanine nucleotides (TGN) and unexpectedly high methylmercaptopurine (MeMP) levels. This predicts a lack of treatment efficacy and excess adverse events; however studies on the effect of thiopurine hypermethylation (TH) in adult IBD patients are lacking. Importantly, where identified TH can be circumvented with the use of low dose AZA/MP and allopurinol. The aim of this study is to characterise the impact of TH in IBD patients and determine if thiopurine metabolite profiles at week 4 of treatment can predict its occurrence to allow early combination treatment. Methods 273 patients with IBD, who were anti-TNF-α therapy naive and matched for red blood cell thiopurine-S-methyltransferase activity, were retrospectively identified. Of these 181 patients demonstrated average MeMP:TGN ratios Results The average MeMP:TGN ratios in those with and without TH were 21.0 and 2.52 respectively (p = 6.17 at week 4 accurately predicted TH (ratio ≥11) after 12 weeks of therapy (AUC = 0.839; p = Conclusion TH is associated with an excess of thiopurine treatment failures as monotherapy immunosuppression during the first 12 months of treatment. We also confirm its association with hepatotoxicity. A MeMP:TGN >6.17 may be useful in early identification of patients likely to benefit from combination treatment. Disclosure of Interest None Declared.