title: [Thiopurine methyltransferase activity in inflammatory bowel disease. A study on 7046 Spanish patients].
abstract: OBJECTIVE
  Our objective was to assess the activity of thiopurine methyltransferase (TPMT) in a very large number of Spanish patients with inflammatory bowel disease (IBD), to evaluate the influence of several variables (including azathioprine or 6-mercaptopurine) on that activity, and to know the proportion of patients with low TPMT activity and therefore high risk of myelotoxicity when treated with these drugs.
  
  
  METHODS
  TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several variables and TPMT values was assessed by multiple lineal regression.
  
  
  RESULTS
  7046 patients were included (mean age: 37 years; 53% males): 70% with Crohn's disease, 22% with ulcerative colitis, and 8% with indeterminate colitis. Mean TPMT value was 20 (6) U/ml RBCs (minimum 0 and maximum 46). TPMT activity distribution was as follows: low levels (< 5 U/ml), 0.5%; intermediate (5-13.7), 11.1%; and high (> or = 13.8), 88.4%. TPMT values did not follow a normal distribution (p < 0.001). In the univariate study, statistically significant differences (p < 0.001), yet of doubtly clinical significance because its minimal magnitude, were demonstrated in TPMT values depending on age, sex, type of disease, and treatment with azathioprine/6-mercaptopurine. In the multivariate study, the variables associated with TPMT activity were: sex, treatment with 5-aminosalicylates, steroids and azathioprine/6-mercaptopurine.
  
  
  CONCLUSIONS
  This study shows that 0.5% of the Spanish patients with IBD have low TPMT activity (< 5 U/ml RBCs), a figure similar to that reported in other countries, these patients being at higher risk of myelotoxicity when treated with azathioprine or 6-mercaptopurine. The drugs usually prescribed for the treatment of IBD, including 5-aminosalicylates and azathioprine/6-mercaptopurine, do not seem to modify in a clinically relevant manner TPMT activity.
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Universidad Autónoma, Madrid, Spain. gisbert@meditex.es
authors.forename: Javier P
authors.initials: JP
authors.lastname: Gisbert
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomollón
authors.forename: Carlos
authors.initials: C
authors.lastname: Cara
authors.forename: Marta
authors.initials: M
authors.lastname: Luna
authors.forename: Yago
authors.initials: Y
authors.lastname: González-Lama
authors.forename: José María
authors.initials: JM
authors.lastname: Pajares
authors.forename: José
authors.initials: J
authors.lastname: Maté
authors.forename: Luis G
authors.initials: LG
authors.lastname: Guijarro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000201:enzymology*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D008780:Methyltransferases / Q000097:blood*; D008875:Middle Aged
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine