Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine

B A Kaskas; E Louis; U Hindorf; E Schaeffeler; J Deflandre; F Graepler; K Schmiegelow; M Gregor; U M Zanger; M Eichelbaum; M Schwab

doi:10.1136/gut.52.1.140

Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine

B A Kaskas, E Louis, U Hindorf, E Schaeffeler, J Deflandre, F Graepler, K Schmiegelow, M Gregor, U M Zanger, M Eichelbaum, M Schwab

Afdeling for Børn og Unge JMC

147 Citationer (Scopus)

Abstract

Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.

Originalsprog	Engelsk
Tidsskrift	Gut
Vol/bind	52
Udgave nummer	1
Sider (fra-til)	140-2
Antal sider	3
ISSN	0017-5749
DOI	https://doi.org/10.1136/gut.52.1.140
Status	Udgivet - jan. 2003

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10.1136/gut.52.1.140

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title = "Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine",

abstract = "Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.",

keywords = "Adult, Azathioprine/administration & dosage, Crohn Disease/drug therapy, Drug Administration Schedule, Female, Humans, Immunosuppressive Agents/administration & dosage, Male, Methyltransferases/deficiency, Treatment Outcome",

author = "Kaskas, {B A} and E Louis and U Hindorf and E Schaeffeler and J Deflandre and F Graepler and K Schmiegelow and M Gregor and Zanger, {U M} and M Eichelbaum and M Schwab",

year = "2003",

month = jan,

doi = "10.1136/gut.52.1.140",

language = "English",

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T1 - Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine

AU - Kaskas, B A

AU - Louis, E

AU - Hindorf, U

AU - Schaeffeler, E

AU - Deflandre, J

AU - Graepler, F

AU - Schmiegelow, K

AU - Gregor, M

AU - Zanger, U M

AU - Eichelbaum, M

AU - Schwab, M

PY - 2003/1

Y1 - 2003/1

N2 - Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.

AB - Thiopurine S-methyltransferase (TPMT) deficient patients develop life threatening haematotoxicity (for example, pancytopenia) when treated with a standard dose of azathioprine (AZA) and 6-mercaptopurine (6-MP) due to excessive accumulation of cytotoxic metabolites. At present, it is generally recommended that these patients should not receive AZA or 6-MP treatment for inflammatory bowel disease. We report for the first time that Crohn's disease patients with TPMT deficiency can be successfully treated with AZA. We illustrate this with three cases where treatment has been successful and toxicity has been avoided by carefully titrating the drug dose. Thus very low TPMT activity demands pharmacogenetically guided dosing.

KW - Adult

KW - Azathioprine/administration & dosage

KW - Crohn Disease/drug therapy

KW - Drug Administration Schedule

KW - Female

KW - Humans

KW - Immunosuppressive Agents/administration & dosage

KW - Male

KW - Methyltransferases/deficiency

KW - Treatment Outcome

U2 - 10.1136/gut.52.1.140

DO - 10.1136/gut.52.1.140

M3 - Journal article

C2 - 12477776

SN - 0017-5749

VL - 52

SP - 140

EP - 142

JO - Gut

JF - Gut

IS - 1

ER -

Safe treatment of thiopurine S-methyltransferase deficient Crohn's disease patients with azathioprine

Abstract

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