Fecal calprotectin is significantly linked to azathioprine metabolite concentrations in Crohn's disease. Issue 1 (January 2019)

• Record Type: Journal Article
• Authors: Essmann, Julian; Keil, Carsten; Unruh, Olesya; Otte, Anita; Manns, Michael P.; Bachmann, Oliver
• Is Part Of: European journal of gastroenterology & hepatology. Volume 31:Issue 1(2019)
• Publication Date: 2019-01
• Subjects: azathioprine -- drug monitoring -- fecal calprotectin -- inflammatory bowel disease; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Digestive organs -- Diseases; Liver -- Diseases; Periodicals; 616.33
• DOI: 10.1097/MEG.0000000000001262
• Languages: English
• ISSNs: 0954-691X

Abstract

Abstract : Background: The value of therapeutic drug monitoring during azathioprine (AZA) therapy with respect to clinical outcomes has been convincingly demonstrated in recent meta-analyses. However, the association between AZA metabolites and the mucosal state in inflammatory bowel disease is largely unclear. Aims: We investigated the association between AZA's active metabolite 6-thioguanine nucleotides (6-TGN) and fecal calprotectin (FC) as a well-validated surrogate marker of mucosal inflammation in patients with Crohn's disease (CD) on AZA monotherapy. Patients and methods: Of 443 6-TGN measurements, 140 values from 88 patients with CD on AZA monotherapy visiting the inflammatory bowel disease outpatient clinic between 2009 and 2016 were retrospectively analyzed. In a subcohort with serial 6-TGN measurements, longitudinal FC measurements in patients with versus without intervention (dose increase, allopurinol, and education) were assessed. Results: In patients with 6-TGN concentrations within a predefined range (250–450 pmol/8×10 8 red blood cells), FC was significantly lower (median: 119.5 vs. 327.2 mg/kg, P =0.003), and hemoglobin as well as serum protein concentrations were significantly higher than in patients with 6-TGN outside of this range. C-reactive protein and transferrin saturation were not different. In the longitudinal cohort, 6-TGN increased in the intervention group, but only a minority reached the defined range; no significant change in FC was observed. Conclusion: This study is the first to show that in patients with CD receiving AZA monotherapy, 6-TGN concentrations within a defined range (250–450 pmol/8×10 8 red blood cells) are associated with significantly lower FC. A treat-to-target concept directed by 6-TGN to reach mucosal healing may thus be a promising approach (DRKS00013246). Abstract : Supplemental Digital Content is available in the text.