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.
Dr Hindorf and colleagues from Sweden designed a study to evaluate the possibility of using 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.
The researchers included a total of 55 adult patients with inflammatory bowel disease in this prospective study and the research group followed them for 6 months.
The researchers measured metabolite levels and correlated these levels to outcome and AZA/6-MP dose.
The research team found that the E-6TGN level was significantly related to the TPMT genotype.
The researchers also noted that patients in disease remission had higher E-6TGN levels than patients with disease activity both at baseline and after 6 months.
|Active disease was more frequent among subjects with E-6TGN ≤ 125 nmol/mmol Hb at baseline|
|Scandinavian Journal of Gastroenterology|
The research group found that active disease was more frequent among subjects with E-6TGN ≤ 125 nmol/mmol Hb at baseline, but not at 6 months.
In addition, AZA/6-MP drug dose was positively correlated to E-MeMP levels and E-MeMP/E-6TGN ratio.
Dose changes were positively correlated with the changes in E-MeMP levels and E-MeMP/E-6TGN ratio.
Dr Hindorf conluded, "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."