Screening for azathioprine toxicity: A pharmacoeconomic analysis based on a target case

被引:76
作者
Tavadia, SMB
Mydlarski, PR
Reis, MD
Mittmann, N
Pinkerton, PH
Shear, N
Sauder, DN
机构
[1] Sunnybrook & Womens Coll Hlth Sci Ctr, Div Dermatol, Toronto, ON M4N 3M5, Canada
[2] Sunnybrook & Womens Coll Hlth Sci Ctr, Dermatol Res, Toronto, ON M4N 3M5, Canada
[3] Sunnybrook & Womens Coll Hlth Sci Ctr, Div Clin Pathol, Toronto, ON M4N 3M5, Canada
[4] Sunnybrook & Womens Coll Hlth Sci Ctr, Hope Res Ctr, Toronto, ON M4N 3M5, Canada
关键词
D O I
10.1016/S0190-9622(00)90176-2
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
The risk of azathioprine-induced myelosuppression can be predicted by detecting patients with intermediate or low thiopurine methyltransferase (TPMT) activity. population studies have shown that 89% of whites have high TPMT activity 11% have intermediate TPMT activity, and 0.3% have low TPMT activity. Three specific mutations in the TPMT gene that cause decreased TPMT activity have recently been identified. Patients homozygous for the TPMT mutations have low TPMT activity, and patients heterozygous for TPMT mutations have intermediate TPMT activity. This has led to the development of a technique For TPMT genotype analysis that will identify patients at risk of azathioprine-induced myelosuppression. We report a case of a patient with bullous pemphigoid who experienced azathioprine-induced myelosuppression and who was later found to be homozygous For TPMT mutant alleles. Using the cost of treatment required fur this patient and the estimated population prevalence of TPMT mutations, we examined the cost impact of screening For TPMT mutations in all patients being considered for azathioprine therapy. We calculated that screening is cost-neutral assuming patients humozygous for TPMT mutations experience myelosuppression, and that; it is cost-beneficial assuming patients heterozygous for TPMT mutations also experience myelosuppression while receiving azathioprine. Screening patients For TPMT mutations will reduce the risk of azathioprine-induced myelosuppression, and our study suggests that it may also be a cost-attractive strategy.
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页码:628 / 632
页数:5
相关论文
共 20 条
[1]  
ANSTEY A, 1992, J ROY SOC MED, V85, P752
[2]  
ANSTEY A, 1995, J ROY SOC MED, V88, P155
[3]   Thiopurine methyltransferase genotype predicts therapy-limiting severe toxicity from azathioprine [J].
Black, AJ ;
McLeod, HL ;
Capell, HA ;
Powrie, RH ;
Matowe, LK ;
Pritchard, SC ;
Collie-Duguid, ESR ;
Reid, DM .
ANNALS OF INTERNAL MEDICINE, 1998, 129 (09) :716-718
[4]   THE IMPORTANCE OF THIOPURINE METHYLTRANSFERASE ACTIVITY FOR THE USE OF AZATHIOPRINE IN TRANSPLANT RECIPIENTS [J].
CHOCAIR, PR ;
DULEY, JA ;
SIMMONDS, HA ;
CAMERON, JS .
TRANSPLANTATION, 1992, 53 (05) :1051-1056
[5]   BONE-MARROW TOXICITY CAUSED BY AZATHIOPRINE IN INFLAMMATORY BOWEL-DISEASE - 27 YEARS OF EXPERIENCE [J].
CONNELL, WR ;
KAMM, MA ;
RITCHIE, JK ;
LENNARDJONES, JE .
GUT, 1993, 34 (08) :1081-1085
[6]   Immunosuppressive agents in dermatology - An update [J].
Dutz, JP ;
Ho, VC .
DERMATOLOGIC CLINICS, 1998, 16 (02) :235-+
[7]   THIOPURINE METHYLTRANSFERASE ACTIVITY IN A SAMPLE-POPULATION OF BLACK SUBJECTS IN FLORIDA [J].
JONES, CD ;
SMART, C ;
TITUS, A ;
BLYDEN, G ;
DORVIL, M ;
NWADIKE, N .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1993, 53 (03) :348-353
[8]   AZATHIOPRINE-RELATED BONE-MARROW TOXICITY AND LOW ACTIVITIES OF PURINE ENZYMES IN PATIENTS WITH RHEUMATOID-ARTHRITIS [J].
KERSTENS, PJSM ;
STOLK, JN ;
DEABREU, RA ;
LAMBOOY, LHJ ;
VANDEPUTTE, LBA ;
BOERBOOMS, AAMT .
ARTHRITIS AND RHEUMATISM, 1995, 38 (01) :142-145
[9]   Bullous pemphigoid - The latest in diagnosis, prognosis, and therapy [J].
Korman, NJ .
ARCHIVES OF DERMATOLOGY, 1998, 134 (09) :1137-1141
[10]   Azathioprine-induced severe pancytopenia due to a homozygous two-point mutation of the thiopurine methyltransferase gene in a patient with juvenile HLA-B27-associated spondylarthritis [J].
Leipold, G ;
Schutz, E ;
Haas, JP ;
Oellerich, M .
ARTHRITIS AND RHEUMATISM, 1997, 40 (10) :1896-1898