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 20 February 2018

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Monitoring thiopurine therapy for evaluation of treatment intensity

Erythrocyte-6-thioguanine nucleotide levels were found, in November's Scandinavian Journal of Gastroenterology, to be related to disease activity and hence researchers suggest a clinical use of E-6TGN monitoring in the evaluation of treatment intensity.

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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."

Scandinavian Journal of Gastroenterology; 2004: 39 (11): 1105 - 1112
09 November 2004

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