P170 Azathioprine metabolite (6-TGN) levels within a defined therapeutic range are associated with lower faecal calprotectin in Crohn's disease. (16th January 2018) - Essmann, J
Abstract: Background: Azathioprine/6-mercaptopurine (AZA/6-MP) are first-line immunosuppressants for the treatment of Crohn's disease. While recent studies have reported a positive association of their active metabolite 6-thioguanine (6-TGN) with clinical outcomes, 6-TGN levels have not been correlated with surrogate markers of mucosal healing, which is an increasingly recognised therapeutic goal. We therefore asked whether 6-TGN levels within a defined therapeutic range are associated with lower fecal calprotectin (FC) in Crohn's disease. Methods: 6-TGN and FC levels of 96 Crohn's disease patients (Median age 36 years, 64% female) without further immunosuppressive therapy visiting our IBD outpatient clinic between 2009 and 2016 were retrospectively analysed. In a small sub-cohort with serial 6-TGN measurements, longitudinal FC measurements were evaluated (Registered as DRKS00013246, submission to WHO in progress). Results: In the cross-sectional approach, 6-TGN levels between 31 and 780 pmol/8 × 10 8 red blood cells (RBCs; mean AZA/6-MP dose: 2.27 mg/kg body weight) were observed. In patients with 6-TGN levels within a defined range (250–450 pmol/8 × 10 8 RBCs; n = 34; Estevinho MM JCC 2017), fecal calprotectin levels were significantly lower (median FC 149 vs. 346 mg/kg, Mann–Whitney U test, p = 0.007), and haemoglobin concentrations as well as transferrin saturation levels were significantly higher ( p = 0.014 and p = 0.018, respectively; Mann–Whitney U test) than in patients with lower or higher metabolites. CRP and protein levels were not different. In the small cohort that was followed longitudinally, all patients achieved an increase in 6-TGN levels upon dose escalation, which was paralleled by a decrease in FC in 71 %, but patient number was insufficient for statistical testing. Conclusions: In our retrospective analysis on Crohn's disease patients receiving thiopurine monotherapy, 6-TGN levels within a defined range (250–450 pmol/8 × 10 8 red blood cells) were associated with significantly lower fecal calprotectin levels as a surrogate marker for mucosal healing. A treat-to target concept directed by 6-TGN levels to reach mucosal healing in Crohn's disease appears promising, but requires prospective studies.