Monitoring of long-term thiopurine therapy among adults with inflammatory bowel disease

Background: The immunosuppressive effects of thiopurine drugs are mainly mediated through their intracellular metabolism into active 6-thioguanine nucleotide (6-TGN) metabolites, which are incorporated into DNA. Erythrocyte 6-TGN (E-6TGN) levels have been proposed as an instrument for monitoring treatment. The aim of the study was to use erythrocyte E-6TGN, methylated mercaptopurine (MeMP) metabolites, and thiopurine methyltransferase (TPMT) measurements in a clinical setting to determine the clinical outcome in relation to thiopurine metabolism. Methods: Fifty-five adult patients with inflammatory bowel disease were included in a prospective study and followed for 6 months. Metabolite levels were measured and correlated to outcome and AZA/6-MP dose. Results: The E-6TGN level was significantly related to the TPMT genotype ( P = 0.008). Patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline ( P < 0.05) and after 6 months ( P = 0.02). Active disease was more frequent among subjects with E-6TGN &LE; 125 nmol/mmol Hb at baseline ( P = 0.04), but not at 6 months. AZA/6-MP drug dose was positively correlated to E-MeMP levels (r(s) = 0.48; P < 0.001) and E-MeMP/E-6TGN ratio (r(s) = 0.41; P = 0.002). Dose changes were positively correlated with the changes in E-MeMP levels ( P = 0.01) and E-MeMP/E-6TGN ratio (P = 0.03). Conclusions: E-6TGN level was the only factor in this study related to disease activity, while there was no relationship between AZA/6-MP dose and E-6TGN levels. This finding illustrates the clinical usefulness of E-6TGN monitoring in the evaluation of treatment intensity.