Utilisation of erythrocyte 6-thioguanine metabolite levels to optimise azathioprine therapy in patients with inflammatory bowel disease

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Abstract
BACKGROUND AND AIM The immunosuppressive properties of 6-mercaptopurine and its parent compound azathioprine are mediated by their intracellular metabolism into active 6-thioguanine (6-TG) metabolites. Measurement of erythrocyte 6-TG metabolite levels has been proposed as a useful clinical tool for assessing treatment efficacy in patients with inflammatory bowel disease (IBD). AIM The purpose of the study was to establish a therapeutic index of treatment efficacy based on measurement of erythrocyte 6-TG metabolite levels, and apply it clinically to guide therapy. METHODS Heparinised blood was obtained from 82 adult patients with IBD on long term (more than three months) antimetabolite therapy (63 Crohn's disease; 19 ulcerative colitis). Erythrocyte 6-TG metabolite levels were measured using reverse phase high performance chromatography, and correlated with treatment efficacy. In 22 patients with refractory Crohn's disease despite long term azathioprine therapy, their dosage was increased by 25 mg/day at eight week intervals as needed. Serial erythrocyte 6-TG metabolite levels were measured at each clinic visit and correlated with treatment efficacy. RESULTS Clinical remission, as defined by a low disease index score in patients weaned off or on a low alternate day dose (8 red blood cells in patients with colonic and fistulising Crohn's disease (p8 red blood cells (p250) should be considered for adjunct or alternative forms of immunosuppressive therapy or surgery.