title: Measurement of red blood cell 6-thioguanine nucleotide is beneficial in azathioprine maintenance therapy of Chinese Crohn's disease patients.
abstract: OBJECTIVE
  It remains controversial whether 6-thioguanine nucleotide (6-TGN)-based dose adjusting can be beneficial in azathioprine (AZA) therapy. This study is designed to assess the role of 6-TGN concentrations in maintaining clinical remission in Chinese patients with Crohn's disease (CD).
  
  
  METHODS
  We performed a prospective observational study and collected data of CD patients in the First Affiliated Hospital of Anhui Medical University from June 2013 to April 2014. Demographic material, CD activity index, 6-TGN concentration, and laboratory tests were recorded at baseline and at each visit. In addition, 6-TGN was measured when drug adverse effects occurred. All patients achieved maintenance stage were administered a stable AZA dose at least 3 months before enrollment and were followed up at least 12 months. Thiopurine S-methyltransferase (TPMT) genotype was measured before AZA treatment.
  
  
  RESULTS
  Sixty-nine patients receiving maintenance therapy were analyzed. A positive correlation was found between 6-TGN levels and AZA dose (r = 0.258, p = 0.032). The mean 6-TGN concentration was 302.06 ± 115.84 in the remission group vs. 264.94 ± 164.53 pmol/8 × 10(8) RBC in those with active disease (t = 0.847, p = 0.40), and 197.74 ± 66.54 pmol/8 × 10(8) RBC in patients who relapsed vs. 310.26 ± 122.38 pmol/8 × 10(8) RBC for those in sustained remission (t= -2.541, p = 0.013). In the leukopenia group, the 6-TGN concentration was 469.11 ± 115.53 pmol/8 × 10(8) RBC vs. 257.31 ± 83.74 pmol/8 × 10(8) RBC in the non-leukopenia group (t = 7.622, p < 0.001). There was a significant negative correlation between leukocyte count and 6-TGN concentration (r= -0.326, p = 0.006).
  
  
  CONCLUSIONS
  6-TGN measurement is a helpful method of preventing disease relapse and avoiding leukopenia in individual azathioprine maintenance therapy.
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;
authors.forename: Qiuyuan
authors.initials: Q
authors.lastname: Liu
authors.affiliation: b Department of Pharmacy , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;
authors.forename: Qiao
authors.initials: Q
authors.lastname: Mei
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: a Department of Gastroenterology , The First Affiliated Hospital of Anhui Medical University , Hefei , Anhui , People's Republic of China ;
authors.forename: Naizhong
authors.initials: N
authors.lastname: Hu
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics; D016903:Drug Monitoring / Q000379:methods; D004912:Erythrocytes / Q000737:chemistry; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D008780:Methyltransferases / Q000235:genetics; D011446:Prospective Studies; D013873:Thionucleotides / Q000097:blood*; D055815:Young Adult
chemical_list: D006150:Guanine Nucleotides; D007166:Immunosuppressive Agents; D013873:Thionucleotides; C003964:6-thioguanylic acid; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001379:Azathioprine
keywords: 6-TGN; Azathioprine; Crohn’s disease; individual therapy