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Case report
Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine
  1. B A Kaskas1,
  2. E Louis2,
  3. U Hindorf3,
  4. E Schaeffeler4,
  5. J Deflandre5,
  6. F Graepler1,
  7. K Schmiegelow6,
  8. M Gregor1,
  9. U M Zanger4,
  10. M Eichelbaum4,
  11. M Schwab4
  1. 1Department of Gastroenterology, University Hospital Tübingen, Germany
  2. 2Department of Gastroenterology, University Hospital Liége, Belgium
  3. 3Department of Internal Medicine, Blekinge Hospital, Karlskrona, Sweden
  4. 4Dr Margarete Fischer-Bosch Institute for Clinical Pharmacology, Stuttgart, Germany
  5. 5Department of Gastroenterology, Regional Hospital La Citadelle, Liége, Belgium
  6. 6Department of Pediatrics II, Juliane Marie Centre, National Hospital, Copenhagen, Denmark
  1. Correspondence to:
    Dr BA Kaskas, Division for Inflammation, Infection, and Repair, University of Southampton, School of Medicine, Mailpoint 813, Southampton SO16 6YD, UK; b.kaskas{at}soton.ac.uk

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.

  • inflammatory bowel diseases
  • thiopurine S-methyltransferase
  • azathioprine
  • 6-MP, 6-mercaptopurine
  • 6-TGN, 6-thioguanine nucleotides
  • ALL, acute lymphoblastic leukaemia
  • AZA, azathioprine
  • IBD, inflammatory bowel diseases
  • RBC, red blood cells
  • TPMT, thiopurine S-methyltransferase
  • TIMP, 6-thioinosine-5′-monophosphate
  • 6-MTG, 6-methylthioguanine

https://doi.org/10.1136/gut.52.1.140

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