Role of Thiopurine Methyltransferase Activity in the Safety and Efficacy of Azathioprine in the Treatment of Pemphigus Vulgaris

Firooz, Alireza; Ghandi, N; Hallaji, Zahra; Chams‐Davatchi, Cheyda; Valikhani, Mahin; Davari, M Karbakhsh

doi:10.1001/archderm.144.9.1143

Cited by 16 publications

(9 citation statements)

References 22 publications

(21 reference statements)

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“…10,11 Approximately 90% of individuals have normal to high TPMT activity, 10% have intermediate activity, and 1 in 220 to 300 individuals is homozygous for mutant alleles with low to almost undetectable enzymatic activity. 10,12 Utilizing the phenotypic classification when initiating therapy has allowed both individuals with normal and intermediate activity to be treated with fewer instances of hematopoetic toxicity. 7,13 It particularly helps identify and precludes administration to patients with significant enzyme deficiency who would be at risk for excessive accumulation of active metabolites.…”

Section: Discussionmentioning

confidence: 99%

Oral azathioprine for recalcitrant pediatric atopic dermatitis: Clinical response and thiopurine monitoring

Caufield

Tom

2013

Journal of the American Academy of Dermatology

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Background Azathioprine is prescribed as a corticosteroid-sparing agent for many inflammatory conditions, including refractory atopic dermatitis (AD). There is limited prospective data on its appropriate use and monitoring for children with AD. Objectives This study was designed to assess clinical response to azathioprine, determine the necessity for repeat measurement of thiopurine methyltransferase (TPMT) activity during treatment, and test the utility of measuring levels of the metabolites 6-thioguanine nucleotide (6-TGN) and 6-methylmercaptopurine (6-MMP). Methods Twelve children with severe, recalcitrant AD were treated with oral azathioprine and followed prospectively. Disease severity was determined by the SCORing Atopic Dermatitis Index. Baseline TPMT activity was measured and this was repeated along with 6-TGN and 6-MMP measurement at times of stable improvement, inadequate response, or change in response. Results Azathioprine therapy was associated with clinical improvement in all but one subject. There were few adverse effects. Three subjects showed a significant change in TPMT activity during treatment: two had a mild decrease and one demonstrated enzyme inducibility with an increase from the intermediate to the normal activity range. These changes, but not 6-TGN or 6-MMP levels, inversely correlated with the clinical response to therapy. Limitations Small sample size Conclusions Azathioprine can be of benefit in the treatment of recalcitrant pediatric AD. Repeat assessment of TPMT activity may be helpful for evaluation of non–response or change in response and warrants further study. In contrast, measurement of thiopurine metabolites during treatment was not clinically useful.

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Section: Discussionmentioning

confidence: 99%

Oral azathioprine for recalcitrant pediatric atopic dermatitis: Clinical response and thiopurine monitoring

Caufield

Tom

2013

Journal of the American Academy of Dermatology

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“…We did not measure the thiopurine methyltransferase (TPMT) activity in our patients, due to its unavailability as a routine test in Iran, and because a work done in Iran that could not show any relationship between TPMT activity and either toxic effects or efficacy of azathioprine therapy in PV 10 …”

Section: Methodsmentioning

confidence: 99%

Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris

Chams‐Davatchi

Mortazavizadeh

Daneshpazhooh

et al. 2012

Acad Dermatol Venereol

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“…Importantly, many studies have also highlighted that patients with one variant TPMT allele (intermediate‐range TPMT activity) who receive ‘conventional’ doses of thiopurines may be at greater risk of toxicity from therapy 7,8,47–49 . Unfortunately, there are only limited publications pertaining to patients with dermatological conditions, including one retrospective review of 139 patients with pemphigus vulgaris which failed to demonstrate an association 50 . Therefore, for the purposes of these guidelines, relevant literature for nondermatological indications is also reviewed.…”

Section: 2 the Role Of Thiopurine Methyltransferase Measurement In mentioning

confidence: 99%

British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011

Meggitt

Anstey

Mustapa

et al. 2011

British Journal of Dermatology

112

151

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Role of Thiopurine Methyltransferase Activity in the Safety and Efficacy of Azathioprine in the Treatment of Pemphigus Vulgaris

Abstract: To evaluate the relationship between thiopurine methyltransferase (TPMT) activity and the safety and efficacy of azathioprine sodium in the treatment of pemphigus vulgaris.

Cited by 16 publications

References 22 publications

Oral azathioprine for recalcitrant pediatric atopic dermatitis: Clinical response and thiopurine monitoring

Oral azathioprine for recalcitrant pediatric atopic dermatitis: Clinical response and thiopurine monitoring

Randomized double blind trial of prednisolone and azathioprine, vs. prednisolone and placebo, in the treatment of pemphigus vulgaris

British Association of Dermatologists’ guidelines for the safe and effective prescribing of azathioprine 2011

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