Thiopurine methyltransferase activity and myelosuppression in inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine

BACKGROUND AND OBJECTIVE: We aimed at assessing whether there exists a relationship between thiopurine methyltransferase (TPMT) activity and the incidence of adverse events, especially myelotoxicity, in patients with inflammatory bowel disease treated with azathioprine (AZA) or 6-mercaptopurine (6-MP). PATIENTS AND METHOD: By means of a radiochemical method, we determined the TPMT activity in erythrocytes of patients with inflammatory bowel disease who had received previously or at the time of the study AZA or 6-MP (n = 97). A group of 37 patients who had never been treated with these drugs was included. We studied the relationship between several variables and TPMT values as well as their correlation with adverse events. RESULTS: Mean (SD) TPMT value was 20.8 (5) U/ml erythrocytes (from 7.8 to 32.7). There was no patient with low TPMT levels (< 5); 9% patients had intermediate levels (from 5 to 13.7 U/ml), while 91% displayed high levels (greater than or equal to 13.8 Ulml). There were no differences when comparing TPMT values according to several variables such as age, gender, tobacco consumption, weight, type of inflammatory bowel disease, and treatment with 5-aminosalicylates, steroids or AZA/6-MP. Side effects were seen in 13 out of 97 (13%) patients administered AZA/6-MP. None patient with side effects exhibited low TPMT levels (< 5 U/ml), nor even intermediate levels (5-13.7 U/ml). There were no differences when comparing mean TPMT values in patients with side effects and in those without side effects. CONCLUSIONS: In this study, the usefulness of the determination of the TPMT activity to identify patients with inflammatory bowel disease at risk of myelotoxicity due to AZA or 6-MP has not been confirmed. Therefore, even when the TPMT enzymatic activity is normal, it is necessary to continue performing the periodic laboratory analysis.