An audit of thiopurine methyltransferase genotyping and phenotyping before intended azathioprine treatment for dermatological conditions.
BACKGROUND
Determining thiopurine methyltransferase (TPMT) genotype and phenotype before azathioprine treatment predicts which patients are most likely to develop myelosuppression.


OBJECTIVE
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.
Vestergaard
T
T
Department of Dermatology, Odense University Hospital, Odense, Denmark. tine.vestergaard@ouh.regionsyddanmark.dk
Bygum
A
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000009:adverse effects*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D012871:Skin Diseases / Q000188:drug therapy / Q000235:genetics*; D055815:Young Adult
D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine