Digestive Diseases and Sciences

, Volume 52, Issue 5, pp 1262–1269

Thiopurine Methyltransferase Activity in Spain: A Study of 14,545 Patients

  • Javier P. Gisbert
  • Fernando Gomollón
  • Carlos Cara
  • Marta Luna
  • Yago González-Lama
  • José María Pajares
  • José Maté
  • Luis G. Guijarro
Original Paper

Abstract

We sought to assess the activity of thiopurine methyltransferase (TPMT) in 14,545 Spanish patients with different diseases amenable to treatment with azathioprine/6-mercaptopurine (6-MP), and to evaluate the proportion of patients with low TPMT activity and therefore a higher risk of myelotoxicity with these drugs. TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several clinical variables and TPMT activity was assessed by multiple linear regression. We included 14,545 patients: autoimmune hepatitis (n=359 patients), inflammatory bowel disease (n=7,046), multiple sclerosis (n = 814), myasthenia gravis (n=344), pemphigus (n=133), and other diseases (n=5,849). Mean TPMT activity was 20.1 ± 6 U/mL, but differed depending on the disease (P < .001). TPMT distribution was low (<5) in 0.5%; intermediate (5.0–13.7) in 11.9%; or high (≥13.8) in 87.6%. Only when TPMT activity was considered separately in each disease did it reveal a normal distribution. In the multivariate analysis, gender, hematocrit, and treatment with 5-aminosalicylates/steroids/azathioprine/6-MP statistically influenced TPMT activity, although, probably, in a clinically irrelevant manner. This study shows, in a large sample of 14,545 patients, that 0.5% had low TPMT activity, indicating a higher risk of myelotoxicity with azathioprine/6-MP, a figure similar or slightly higher than that reported in other areas. Nevertheless, the trimodal distribution of TPMT activity varied depending on disease, and the proportion of patients with low activity values ranged from 0–0.8%. The drugs prescribed for the treatment of autoimmune diseases, including azathioprine/6-MP, modified TPMT activity, but the magnitude of this effect was very small and the differences found are probably irrelevant from the clinical point of view.

Keywords

Azathioprine 6-Mercaptopurine Thiopurine methyltransferase TPMT Inflammatory bowel disease Autoimmune hepatitis Multiple sclerosis Myasthenia gravis Pemphigus 

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Copyright information

© Springer Science &#x002B; Business Media, Inc. 2006

Authors and Affiliations

  • Javier P. Gisbert
    • 1
  • Fernando Gomollón
    • 2
  • Carlos Cara
    • 3
  • Marta Luna
    • 1
  • Yago González-Lama
    • 1
  • José María Pajares
    • 1
  • José Maté
    • 1
  • Luis G. Guijarro
    • 4
  1. 1.Servicio de Aparato Digestivo Hospital Universitario de la PrincesaUniversidad AutónomaBoadilla del MonteSpain
  2. 2.Servicio de Aparato DigestivoHospital Clínico UniversitarioZaragozaSpain
  3. 3.Departamento MédicoCelltech UCB PharmaBrusselsBelgium
  4. 4.Unidad de Toxicología Molecular Hepática Departamento de Bioquímica y Biología MolecularUniversidad de AlcaláMadridSpain

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