Thiopurine Dose in Intermediate and Normal Metabolizers of Thiopurine Methyltransferase May Differ Three-Fold

Abstract

Background & Aims: Patients with inflammatory bowel disease (IBD) may have different thiopurine dose requirements in relation to thiopurine methyltransferase (TPMT) genotype and/or phenotype. The purpose of this study was to determine thiopurine dose requirements in intermediate versus normal TPMT metabolism status. Methods: Consecutive patients starting azathioprine or 6-mercaptopurine for IBD were followed up for 9 months. The thiopurine dose was individualized using 6-thioguanine nucleotide (6-TGN) concentrations (range, 235-450 pmol/8 × 108 red blood cells [RBCs]) and clinical status. Additional assessments undertaken every three months included measures of disease activity. Results: Eight (10%) of 77 participants were withdrawn because of protocol violation. Fifty-two (75%) of the remaining 69 subjects (∼90% and 10% with the TPMT*1/*1 and *1/*3 genotypes, respectively) completed follow-up on azathioprine (n = 46) or 6-mercaptopurine (n = 6). The mean initial dose (as azathioprine equivalents) was similar (∼1 mg/kg/d) for the 2 TPMT genotypes, but after 9 months the dose was 50% lower in the TPMT*1/*3 group (0.9 vs 1.8 mg/kg/d, P 235 pmol/8 × 108 RBCs) in patients with IBD might be 1 and 3 mg/kg/d in intermediate and normal metabolizers, respectively. © 2008 AGA Institute.