Therapeutic drug monitoring of thiopurines: Effect of reduced
6-thioguanine nucleotide target levels in IBD patients
Abstract
Aim: The effect of the Dutch nationwide adjustment of reduced 6-TGN
target values (from 600-1200 pmol/8x108 RBC to 320-630 pmol/8x108 RBC)
on toxicity and clinical outcome of thiopurine treatment in patients
with inflammatory bowel disease (IBD) has not yet been established.
Therefore the authors determined the incidence of toxicity-induced
discontinuations and efficacy at both target concentrations. Methods:
This retrospective study was performed in IBD patients treated with
azathioprine or mercaptopurine. Two groups were defined: the former
target (FT) group with target concentrations of 600-1200 pmol/8x10^8
RBC and the adjusted target (AT) group with target concentrations of
320-630 pmol/8x10^8 RBC. Patients were followed for maximum 52 weeks
or until discontinuation of thiopurine therapy. Data were collected from
the local hospital electronic health software of Rijnstate Hospital.
Results: 151 patients were included, 76 in the FT group and 75 in the AT
group. At week 52, 100 out of 150 patients (66%) of the total
population discontinued thiopurine therapy. Forty-eight of this
discontinuations were due toxicity (48%). The estimated cumulative
incidence of toxicity was higher in the FT group compared to the AT
group (47% and 35% respectively, p=0.25). No loss of efficacy was seen
in the AT group. Conclusion: Reduction of the target range may lead to
less toxicity induced discontinuations. In addition, this study did not
find any indication that the reduction of the target range diminished
efficacy.