Choice of azathioprine or 6-mercaptopurine dose based on thiopurine methyltransferase (TPMT) activity to avoid myelosuppression. A prospective study.

ABSTRACT

BACKGROUND/AIMS: To prospectively evaluate whether, in patients with inflammatory bowel disease, the choice of azathioprine (AZA) or 6-mercaptopurine (6-MP) dose based on thiopurine methyltransferase (TPMT) activity prevents myelotoxicity. METHODOLOGY: TPMT activity in red blood cells was measured in 99 patients with Crohn's disease and 32 with ulcerative colitis prior to initiating AZA/6-MP treatment. AZA/6-MP dose was chosen based on TPMT activity, which was again determined one month after starting therapy. Incidence of adverse effects was evaluated for at least 6 months of follow-up. RESULTS: Mean basal TPMT value was 21.6 +/- 5 U/mL. No patient had low levels (< 5 U/mL), 6.9% had intermediate levels (5-13.7 U/mL), and 93.1% had high levels (> 13.8 U/mL). In patients with Crohn's disease, mean TPMT activity significantly decreased after AZA/6-MP therapy, while in patients with ulcerative colitis this activity did not change. Among the 4 patients having myelotoxicity, one had intermediate basal TPMT levels, and 3 even had high levels, but no patient had low levels. CONCLUSIONS: In this prospective study we could not confirm that the choice of AZA/6-MP dose based on TPMT activity prevents myelotoxicity in patients with inflammatory bowel disease. Routine analytical controls should be performed in these patients independently of TPMT activity.