An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions.

摘要

BACKGROUND: Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression. AIM: To evaluate the course of azathioprine treatment in people with TPMT heterozygosity and whether this deterred clinicians in prescribing the drug. METHODS: This was a retrospective analysis on patients who had TPMT assays undertaken with the intention of treating their skin disorder with azathioprine. Primary outcome measurements were: (i) whether or not azathioprine was started, (ii) azathioprine dosage, and (iii) duration of treatment. Secondary outcome measures were the effect of the drug, any reported side-effects and reasons for not starting azathioprine. RESULTS: TPMT assays were undertaken in 212 patients, of whom 90.6% were TPMT wild type and the remaining 9.4% were TPMT heterozygous. None of the patients was TPMT homozygous. Of the 192 wild-type patients, 103 (53.6%) received azathioprine, as did 7 (35%) of the 20 heterozygotes (P = 0.16). Mean azathioprine dose was 84.1 mg/day for wild-type patients and 64.3 mg/day for heterozygotes (P = 0.10). Mean treatment duration was 21.4 and 22.7 weeks for wild-type and heterozygotes, respectively (P = 0.52). Azathioprine treatment was stopped in 4 of 7 heterozygotes and 54 of 103 wild-type patients, because of side-effects, lack of effect or a combination of both. The commonest reason for not starting azathioprine treatment in heterozygous patients was their heterozygosity. For wild-type patients, the reasons were remission of disease or the patient's lack of interest in the treatment. CONCLUSIONS: TPMT heterozygosity was a deterring factor for the prescription of azathioprine in our department, and the dose for wild-type patients was lower than recommended guidelines. Treatment duration and occurrence of adverse effects were similar for heterozygotes and wild-type patients.