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.
authors.affiliation: Department of Gastroenterology, University Hospital Tübingen, Germany. b.kaskas@soton.ac.uk
authors.forename: B A
authors.initials: BA
authors.lastname: Kaskas
authors.forename: E
authors.initials: E
authors.lastname: Louis
authors.forename: U
authors.initials: U
authors.lastname: Hindorf
authors.forename: E
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: J
authors.initials: J
authors.lastname: Deflandre
authors.forename: F
authors.initials: F
authors.lastname: Graepler
authors.forename: K
authors.initials: K
authors.lastname: Schmiegelow
authors.forename: M
authors.initials: M
authors.lastname: Gregor
authors.forename: U M
authors.initials: UM
authors.lastname: Zanger
authors.forename: M
authors.initials: M
authors.lastname: Eichelbaum
authors.forename: M
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage*; D003424:Crohn Disease / Q000188:drug therapy* / Q000201:enzymology*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008780:Methyltransferases / Q000172:deficiency*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine