Measurement of thiopurine methyltransferase activity and azathioprine metabolites in patients with inflammatory bowel disease

Background-Measurement of 6-thioguanine nucleotide concentrations may be us eful for optimising treatment with azathioprine and 6-mercaptopurine. Methods-We conducted a study of 170 patients with inflammatory bowel diseas e treated with azathioprine or 6-mercaptopurine to determine the relationsh ip between 6-thioguanine nucleotide concentrations and both disease activit y, as measured by the inflammatory bowel disease questionnaire (active dise ase < 170, remission greater than or equal to 170) and leucopenia. Blood wa s submitted for whole blood 6-thioguanine nucleotide concentration and leuc ocyte count. Results-Mean (SD) inflammatory bowel disease questionnaire score was 176 (3 2). There was no correlation between inflammatory bowel disease questionnai re scores and 6-thioguanine nucleotide concentrations (r(s) = -0.09, p = 0. 24). Median 6-thioguanine nucleotide concentrations in 56 patients with act ive disease and 114 patients in remission were similar (139 v 131 pmol/8 x 10(8) red blood cells; p = 0.26). There was no correlation between 6-thiogu anine nucleotide concentrations and leucocyte counts. Conclusions-In patients with inflammatory bowel disease treated with azathi oprine or 6-mercaptopurine, 6-thioguanine nucleotide concentrations did not correlate with disease activity, as measured by the inflammatory bowel dis ease questionnaire, or leucocyte count. These findings are discrepant with most previous studies, possibly due to selection of responding patients who tolerated the medications. A prospective, randomised, dose optimisation tr ial using 6-thioguanine nucleotide concentrations is warranted.