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1 November 1998 | Volume 129 Issue 9 | Pages 716-718
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.
Author and Article Information
From the University of Aberdeen and Aberdeen Royal Hospitals Trust and Glasgow Royal Infirmary, Glasgow, United Kingdom.
BRIEF COMMUNICATION
Thiopurine Methyltransferase Genotype Predicts Therapy-Limiting Severe Toxicity from Azathioprine
Acknowledgments: The authors thank research nurse Rosemary Hampson.
Grant Support: In part by the Wellcome Trust (046607) and the Beit Trust. Dr. Reid is also supported by the Arthritis Research Campaign.
Requests for Reprints: Howard L. McLeod, PharmD, Department of Medicine & Therapeutics, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, United Kingdom; e-mail, h.l.mcleod@abdn.ac.uk.
Current Author Addresses: Dr. Black: The Osteoporosis Research Unit, Aberdeen Royal Hospitals Trust, Aberdeen AB25 2ZD, United Kingdom.
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