P272 Azathioprine drug monitoring and faecal calprotectin levels in ulcerative colitis
C. Keil*1, L. Püschel1, A. Otte2, M. P. Manns1, O. Bachmann1
1Hannover Medical School, Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover, Germany, 2University Medical Centre, Institute for Clinical Chemistry, Göttingen, Germany
Azathioprine/6-mercaptopurine (AZA/6-MP) is one of the first-line immunosuppressants for the treatment of ulcerative colitis, but most guidelines argue against the routine use of 6-thioguanine (TGN) level monitoring in view of inconclusive studies on its value regarding the achievement of clinical endpoints. Despite the increasing significance of markers of mucosal healing, data on their association with 6-TGN levels in UC are sparse. We therefore asked whether 6-TGN levels are inversely related to faecal calprotectin (FC) levels in AZA/6-MP-treated clinically quiescent ulcerative colitis patients.
Out of 83 patients with available 6-TGN level and FC measurements visiting the IBD clinic of Hannover Medical School from 2008 to 2014, 25 patients on AZA/6-MP monotherapy in clinical remission (SSCAI < 5) were identified. In a small sub-cohort with serial 6-TGN measurements and AZA/6-MP dose adjustment, longitudinal FC measurements were evaluated.
In the cross-sectional approach, 6-TGN levels ranged from 32 to 839 pmol/8x108 red blood cells (RBCs) (median 204). There was no statistically significant association between 6-TGN levels and FC levels. Further, there was no statistically significant difference between FC levels of patients above and below the previously published 6-TGN threshold of 236 pmol/8 x 108 RBCs (p = 0,130). In the small cohort that was followed longitudinally, 6 of 11 patients received a dose adjustment, 4 of which achieved an increase in 6-TGN levels above 236 pmol/8 x 108 RBCs in combination with a decrease in their FC levels (50% with levels < 100 µg/g), but patient number was insufficient to perform statistical analysis.
In our retrospective analysis on clinically quiescent ulcerative colitis patients receiving thiopurine monotherapy, no statistically significant correlation between 6-TGN levels and faecal calprotectin was observed. However, a considerable fraction of patients experienced a decrease in their FC levels after exceeding the threshold of 236 pmol/8 x 108 RBCs following dose adjustment. A treat-to-target concept directed by 6-TGN levels to reach mucosal healing thus warrants further studies.