We therefore sought to determine whether the assessment of TPMT activity before administration of AZA would predict toxicity and could therefore be used to reduce the costs related to the standard biochemical screening for, and management of, AZA-induced adverse events. The present study was performed between September 2002 and August 2003, and was approved by the Health Research Ethics Board at the University of Alberta, Edmonton, Alberta. Twenty-nine patients aged 12 years and older with either CD (23 patients) or ulcerative colitis (six patients) who were starting AZA treatment were recruited for this randomized prospective study.
Patients who had received a blood transfusion within 90 days, or who had leukopenia (white blood cell count less than 4×108/L), thrombocytopenia (platelets less than 100,000/L), pancytopenia, elevated liver enzymes (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] or gamma-glutamyltransferase [GGT] greater than 2 x upper limit of normal), or elevated lipase (greater than 2 x upper limit of normal) or who were on allopurinol were excluded from the study. The patients’ reasons for starting immunosuppressive treatment included steroid dependency (26 patients) and maintenance of remission after surgical resection (three patients). Table 1 summarizes the characteristics of the patients at the time of randomization .
TABLE 1 Patient demographics
|Group 1 (n=15)||Group 2 (n=14)|
|Age, years (mean ± SD)||31.4±12.5||40.6±16.4|
|(range 12 to 58)||(range 15 to 80)|
|Indication for azathioprine therapy, n|
|Concomitant medications, n|
Group 1: No thiopurine methyltransferase (TPMT) assay before initiation of azathioprine; Group 2: TPMT assay performed before initiation of azathio-prine