title: Screening for azathioprine toxicity: a pharmacoeconomic analysis based on a target case.
abstract: 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 for 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 homozygous 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.
authors.affiliation: Dermatology Research, Division of Dermatology, Sunnybrook and Women's College Health Science Centre, Toronto, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Tavadia
authors.forename: P R
authors.initials: PR
authors.lastname: Mydlarski
authors.forename: M D
authors.initials: MD
authors.lastname: Reis
authors.forename: N
authors.initials: N
authors.lastname: Mittmann
authors.forename: P H
authors.initials: PH
authors.lastname: Pinkerton
authors.forename: N
authors.initials: N
authors.lastname: Shear
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000191:economics; D003365:Costs and Cost Analysis; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000191:economics; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000139:chemically induced*; D010391:Pemphigoid, Bullous / Q000188:drug therapy
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine