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

• Published in: Scandinavian journal of gastroenterology Vol. 39; no. 11; p. 1105
• Main Authors: Hindorf, U, Lyrenäs, E, Nilsson, A, Schmiegelow, K
• Format: Journal Article
• Language: English
• Published: England 01.11.2004
• Subjects: Adolescent; Adult; Azathioprine - adverse effects; Azathioprine - therapeutic use; Drug Monitoring; Erythrocytes - chemistry; Female; Genotype; Guanine Nucleotides - blood; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Inflammatory Bowel Diseases - blood; Inflammatory Bowel Diseases - drug therapy; Male; Mercaptopurine - adverse effects; Mercaptopurine - analogs & derivatives; Mercaptopurine - blood; Mercaptopurine - therapeutic use; Methyltransferases - blood; Methyltransferases - genetics; Middle Aged; Sulfasalazine - therapeutic use; Thionucleotides - blood
• ISSN: 0036-5521
• DOI: 10.1080/00365520410007980

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. 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. 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 < or = 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 = 0.48; P < 0.001) and E-MeMP/E-6TGN ratio (r = 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). 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.