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

Tavadia, Sherine M.B.; Mydlarski, P. Régine; Reis, Marciano D.; Mittmann, Nicole; Pinkerton, P. H.; Shear, Neil H.; Sauder, Daniel N.

doi:10.1067/mjd.2000.103980

Cited by 76 publications

(31 citation statements)

References 15 publications

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“…Given that all major TPMT mutant alleles are present in the Brazilian population, it would be a good clinical practice to genotype all of them as previously suggested. 40 To avoid 6-MP concentration-dependent side effects, genotyping tests before the initiation of therapy could identify patients with an unacceptable mortality and/or morbidity risks. Indeed, we were able to identify, albeit retrospectively, that both patients with ALL who had severe drug side effects necessitating dose reductions, were heterozygous for the mutant alleles TPMT*2 or TPMT*3C.…”

Section: Discussionmentioning

confidence: 99%

Thiopurine methyltransferase polymorphisms in a Brazilian population

et al. 2003

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Thiopurine methyltransferase (TPMT) catalyses the S-methylation of thiopurine drugs. Low-activity phenotypes are correlated with several mutations in the TPMT gene. Polymorphisms of TPMT have been reported for Caucasians, African-Americans and Asians. Since ethnic differences have been demonstrated worldwide, it remains to be elucidated in Brazil. The Brazilian population is the result of five centuries of interethnic crosses between peoples from almost all continents as well as autochthonous Amerindians, all forming the fifth largest and one of the most heterogeneous populations in the world. The frequency of six allelic variants of the TPMT gene, *2 (G238C) (2.2%), *3A (G460A and A719G) (1.5%), *3B (G460A) (0.2%), *3C (A719G) (1.0%), *5 (0%) and *6 (0%) were determined in Brazilian subjects using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. This study provides the first analysis of TPMT mutant allele frequency in a sample of the Brazilian population.

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Section: Discussionmentioning

confidence: 99%

Thiopurine methyltransferase polymorphisms in a Brazilian population

et al. 2003

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“…Two of these 113 patients had TPMT activity >50 pmol ⁄ h ⁄ mgHb. Sixteen (12.3%) patients had TPMT activity within the intermediate range (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) and one had TPMT deficiency with activity of 2 pmol ⁄ h ⁄ mg Hb. One hundred and nineteen patients had a wild-type genotype and 11 were heterozygous (eight patients TPMT*3A, three patients TPMT*3C).…”

Section: Correlation Between Tpmt Genotype and Activitymentioning

confidence: 99%

“…The largest study examining TPMT gene polymorphisms in patients with thiopurine-related marrow toxicity reported that 29% of cases occurred in individuals with variant genotypes. 19 Although the assessment of TPMT status is not a substitute for blood count monitoring, its employment in routine practice has been estimated to be cost-effective in the management of IBD 20,21 as well as in rheumatological 22,23 and dermatological 24 conditions.…”

Section: Introductionmentioning

confidence: 99%

Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease

Winter¹,

Gaffney²,

Shapiro³

et al. 2007

Aliment Pharmacol Ther

100

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“…Although .70% of myelosuppression related to azathioprine use is not associated with TPMT polymorphism [13,18,19], screening as few as 20 patients for TPMT deficiency can prevent one adverse event over 6 months of therapy [20]. Furthermore, pharmacoeconomic models and prospective studies have demonstrated that genotype or phenotype screening for TPMT polymorphisms is cost-effective in patients with rheumatological disorders [20], inflammatory bowel disease [21,22], paediatric leukaemia [23] and autoimmune skin disease [24]. Other small prospective screening studies of TPMT activity have not adequately predicted toxicity in patients with inflammatory bowel disease [25,26].…”

Section: Discussionmentioning

confidence: 99%

Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase

Perri

Cole²,

Friedman³

et al. 2007

Eur Respir J

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Current guidelines support the use of corticosteroids and azathioprine as one possible treatment strategy for idiopathic pulmonary fibrosis (IPF). However, some patients with genetic polymorphisms of thiopurine methyltransferase (TPMT) are at risk of severe azathioprine myelotoxicity.The current authors present the case of an 85-yr-old Caucasian male with IPF who developed diffuse alveolar haemorrhage as a complication of azathioprine-induced myelosuppression.Leukocyte genetic TPMT testing revealed that the patient had homozygous polymorphisms associated with the absence of TPMT activity and severe azathioprine-induced myelotoxicity.Thiopurine methyltransferase deficiency should be considered in patients who develop leukopenia early in treatment with azathiopurine, or who present with severe marrow suppression at usual doses. For centres with equipped laboratories, a dosing suggestion is provided based on thiopurine methyltransferase testing. Even with screening strategies, frequent monitoring of complete blood count and liver biochemistry should remain the mainstay of surveillance for azathioprine toxicity.

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

Cited by 76 publications

References 15 publications

Thiopurine methyltransferase polymorphisms in a Brazilian population

Thiopurine methyltransferase polymorphisms in a Brazilian population

Assessment of thiopurine methyltransferase enzyme activity is superior to genotype in predicting myelosuppression following azathioprine therapy in patients with inflammatory bowel disease

Azathioprine and diffuse alveolar haemorrhage: the pharmacogenetics of thiopurine methyltransferase

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