Thiopurine methyltransferase enzyme activity determination: Discussion (Part 2)
TPMT activity can be influenced not only by TPMT genotype but by concomitant medications. TPMT activity can be inhibited by sulfasalazine, olsalazine, balsalazide, mesalamine and, to a lesser extent, by furosemide, thiazide diuretics and nonsteroidal anti-inflammatory drugs. Thus, the concomitant use of mesalamine could lead to increased toxicity. Seven patients in the present study were using mesalamine concomitantly with AZA. None of the patients on mesalamine developed AZA-related adverse events.
In the present study, the prospective assessment of TPMT enzyme activity before the initiation of AZA therapy for patients with IBD in group 2 was associated with increased direct cost ($348.87 per patient) compared with group 1 ($300.11 per patient), in which the TPMT assay was not performed. This increase in cost was almost fully attributed to the cost of the TPMT assay (valued at $50.00). More importantly, however, was the fact that knowing TPMT activity did not markedly reduce the cost of additional laboratory and diagnostic tests in patients over the duration of the study (group 2; $37.77 per patient versus group 1; $39.21 per patient). The reason for this cost similarity is the fact that additional testing was predominately driven by adverse events. The adverse events were similar in both groups and also not generally those related to AZA (Table 3). It is important to note that the majority of the costs in this study were due to the protocol-driven routine laboratory investigations and, thus, were equal in both groups.