Thiopurine methyltransferase enzyme activity determination: Discussion (Part 1)
Knowing TPMT activity and starting AZA in either a ‘step-in’ or ‘step-up’ approach did not alter the number of adverse events related to AZA nor the number of withdrawals from the study. This is likely because most of the adverse events necessitating withdrawal were those that are generally thought to be independent of AZA metabolite levels . One patient developed leukopenia and two patients developed elevated liver enzymes in the group in which TPMT activity was not initially known (group 1; ‘step-up’ AZA dosing); however, retrospective testing confirmed normal TPMT activity in these patients. This is consistent with previous reports where myelo-suppression and elevated liver enzymes can occur despite normal TPMT genotype and activity. medicines-for-diabetes.comFurthermore, these adverse events can occur months or even years after successful dosing with AZA . Nevertheless, it is important to point out that this study did not find low TPMT activity in any of its subjects. Identifying a low TPMT activity would predict the TPMTH/TPMTL or TPMTL/TPMTL genotype and likely contraindicate the use of AZA. Even though low TPMT activity may abrogate the use of AZA, demonstrating normal TPMT activity before dosing with AZA was not a positive or negative predictor of adverse events.