The relation between Thiopurine Methyl Transferase activity and efficacy and side effects of Azathioprine in patients with Pemphigus Vulgaris

Abstract

Background and aim: Azathioprine is the most widely used immunosuppressive agent as an adjunct to corticosteroids in the treatment of pemphigus vulgaris (PV). Thiopurine methyl transferase (TPMT) is a key enzyme in azathioprine metabolism and a genetic polymorphism controls its activity in human tissue. TPMT activity can provide a rational basis to determine suitable dose of azathioprine, theoretically. The aim of this study was to evaluate the clinical relevancy of this hypothesis in PV patients.<br />Materials and Methods: In this cross sectional study in Razi Hospital, the activity of TPMT in the red blood cells of 52 PV patients who received azathioprine for at least 12 months and 29 PV patients who did not receive this drug was measured and correlated to the clinical response and side effects observed.<br />Results:The mean of TPMT activity was not significantly different in patients with unfavourable response, comparing to patients with favorable response to azathioprine (P=0.087). No relationship was observed between total dose of corticosteroid and TPMT activity (r=0.089, P=0.583). There was no difference between the mean of TPMT activity in patients receiving azathioprine and those not receiving this drug (P=0.36).<br />Conclusion: A direct relationship was not observed between TPMT activity and clinical efficacy and side effects in PV patients under treatment with azathioprine. Larger prospective studies in more homogenous patients are needed to evaluate the clinical relevance of TPMT polymorphism and to determine accurate azathioprine dosing guidelines based on TPMT activity.