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


METHODS
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.
Gisbert
Javier P
JP
Gastroenterology Unit, Hospital Universitario de la Princesa, Universidad Autónoma, Madrid, Spain. gisbert@meditex.es
Luna
Marta
M
Maté
José
J
González-Guijarro
Luis
L
Cara
Carlos
C
Pajares
José María
JM
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000201:enzymology; D003424:Crohn Disease / Q000188:drug therapy* / Q000201:enzymology; D016903:Drug Monitoring; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007970:Leukopenia / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage* / Q000009:adverse effects; D008780:Methyltransferases / Q000378:metabolism*; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine