Fecal calprotectin is significantly linked to azathioprine metabolite concentrations in Crohn's disease.

Autor:	Essmann J; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover., Keil C; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover., Unruh O; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover., Otte A; Institute for Clinical Chemistry, University Medical Center Göttingen, Göttingen, Germany., Manns MP; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover., Bachmann O; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover.
Jazyk:	angličtina
Zdroj:	European journal of gastroenterology & hepatology [Eur J Gastroenterol Hepatol] 2019 Jan; Vol. 31 (1), pp. 99-108.
DOI:	10.1097/MEG.0000000000001262
Abstrakt:	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 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 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).
Databáze:	MEDLINE
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