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Ann Intern Med. 1998 Nov 1;129(9):716-8.

Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine.

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  • 1University of Aberdeen and Aberdeen Royal Hospitals Trust, United Kingdom.

Abstract

BACKGROUND:

Substantial hematologic toxicity limits the use of azathioprine.

OBJECTIVE:

To evaluate 1) polymorphic inactivation of azathioprine by thiopurine methyltransferase and 2) clinical toxicity.

DESIGN:

Prospective cohort study.

SETTING:

Two rheumatology units.

PATIENTS:

67 patients for whom azathioprine was prescribed as second-line therapy for rheumatic disease.

MEASUREMENTS:

Polymerase chain reaction-based assays were used to detect mutations in thiopurine methyltransferase. The primary end point was discontinuation of azathioprine therapy because of toxicity.

RESULTS:

Six of 67 patients (9%) were heterozygous for mutant thiopurine methyltransferase alleles. Five of the 6 patients discontinued therapy within 1 month of starting treatment because of low leukocyte counts. The sixth patient did not adhere to treatment. Patients with wild-type thiopurine methyltransferase alleles received therapy longer than did patients with mutant alleles (median duration of therapy, 39 weeks [range, 6 to 180 weeks] and 2 weeks [range, 2 to 4 weeks], respectively; P = 0.018).

CONCLUSION:

Analysis of thiopurine methyltransferase genotype is a quick way to identify patients at risk for acute toxicity from azathioprine.

PMID:
9841604
[PubMed - indexed for MEDLINE]
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