title: Concentrations of 6-thioguanine nucleotide correlate with trough levels of infliximab in patients with inflammatory bowel disease on combination therapy.
abstract: OBJECTIVE
  In patients with inflammatory bowel diseases, the combination of infliximab and thiopurines (such as 6-thioguanine) is more effective treatment than monotherapy. We assessed the correlation between serum levels of 6-thioguanine (6-TGN) and infliximab levels or antibodies to infliximab (ATI).
  
  
  METHODS
  We performed a cross-sectional study of 72 patients receiving maintenance therapy with infliximab and a thiopurine for inflammatory bowel disease at the Crohn's and Colitis Center of the University of Miami, FL. We collected clinical, endoscopic, and biochemical data, and levels of thiopurine metabolites. The primary outcomes were trough level of infliximab and the presence of ATI.
  
  
  RESULTS
  Levels of 6-TGN correlated with those of infliximab (ρ, 0.53; P < .0001). The cut-off point of 6-TGN that best predicted a higher level of infliximab was 125 pmol/8 × 10(8) red blood cells (RBCs) (area under receiver operating characteristic, 0.86; P < .001). Patients in the lowest quartile of 6-TGN had infliximab levels that were similar to patients on no thiopurines (4.3 vs. 4.8 mcg/mL, respectively; P = .8). An infliximab level of 8.3 mcg/mL or greater was associated with mucosal healing. Only 8 patients (11%) had detectable ATI. Patients with 6-TGN levels less than 125 pmol/8 × 10(8) RBCs were significantly more likely to have ATI (odds ratio, 1.3; 95% confidence interval, 2.3-72.5; P < .01).
  
  
  CONCLUSIONS
  Although 6-TGN levels of greater than 230 pmol/8 × 10(8) RBCs have been associated with improved outcomes in patients on monotherapy, a level of 6-thioguanine of 125 pmol/8 × 10(8) RBCs or greater may be adequate to achieve therapeutic levels of infliximab. In the long term, this may minimize the toxicity for patients on combination therapy.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Yarur
authors.affiliation: University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Maddie J
authors.initials: MJ
authors.lastname: Kubiliun
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Frank
authors.initials: F
authors.lastname: Czul
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Sussman
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Quintero
authors.affiliation: Prometheus Laboratories, San Diego, California.
authors.forename: Anjali
authors.initials: A
authors.lastname: Jain
authors.affiliation: Prometheus Laboratories, San Diego, California.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Drake
authors.affiliation: Prometheus Laboratories, San Diego, California.
authors.forename: Scott I
authors.initials: SI
authors.lastname: Hauenstein
authors.affiliation: Prometheus Laboratories, San Diego, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Lockton
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Amar R
authors.initials: AR
authors.lastname: Deshpande
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida.
authors.forename: Jamie S
authors.initials: JS
authors.lastname: Barkin
authors.affiliation: Prometheus Laboratories, San Diego, California.
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Miami, Miller School of Medicine, Miami, Florida. Electronic address: mabreu1@med.miami.edu.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Abreu
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006150:Guanine Nucleotides / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D007155:Immunologic Factors / Q000097:blood* / Q000493:pharmacokinetics*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D000069285:Infliximab / Q000097:blood* / Q000493:pharmacokinetics*; D008297:Male; D044967:Serum / Q000737:chemistry; D013873:Thionucleotides / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D000906:Antibodies; D006150:Guanine Nucleotides; D007155:Immunologic Factors; D013873:Thionucleotides; C003964:6-thioguanylic acid; D000069285:Infliximab
keywords: Azathioprine; Crohn's Disease; Drug Levels; Mercaptopurine; Ulcerative Colitis