Thiopurine methyltransferase enzyme activity determination: Discussion (Part 3)
One could hypothesize that knowing a normal TPMT activity would eliminate the need for routine testing and, thereby, significantly reduce costs. Unfortunately, this is unlikely to be the case, because this and other studies have demonstrated myelotoxicity and hepatotoxicity in the presence of normal TPMT activity. Physicians are thus likely to continue to perform hematological and biochemical testing on a regular basis .
None of the patients in the present study were homozygous for TPMT deficiency. It has recently been suggested that TPMT genotyping would be cost-effective in identifying the one in 300 individuals homogenous for TPMT deficiency. Indeed, it is this group in whom acute and severe myelosuppression is most frequent and has led to the current clinical practice of subtherapeutic dosing and frequent biochemical monitoring.
The role of prospective TPMT testing, and thus ‘step-in’ versus ‘step-up’ therapy, on the efficacy of AZA therapy was not addressed in the present study and is the objective of a multicentre, randomized, controlled trial currently underway. Furthermore, this ongoing clinical trial will provide a larger sample size to substantiate the role of TPMT determination in the prediction of acute AZA adverse events. In summary, the prospective assessment of a normal TPMT enzyme activity before initiating AZA therapy in IBD patients added additional cost and did not predict AZA-induced toxicity.