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P197 Use of 6-thioguanine nucleotide concentration test in the management of patients with Crohn’s disease in Korea

T. J. Kim*, J. Lee, E.R. Kim, S. N. Hong, D.K. Chang, Y.-H. Kim

Samsung Medical Centre, Seoul, South Korea

Background

The association between 6-TGN and clinical remission remains a matter of debate in IBD.1,2,3,4 In addition, there were few reports for adults in Korea.5 The aim of this cross-sectional study was to compare metabolite level in active disease and remission state patients with Crohn’s disease (CD) undergoing thiopurine maintenance treatment.

Methods

From April to December 2014, 140 patients were included for analysis. The patients were classified as 2 groups. The responder group was comprised of patients with a CDAI score ≤ 150 undergoing azathioprine or 6-mercaptopurine therapy. Patients with CDAI > 150 or who received anti-tumour necrosis factor agent as a ‘step-up’ treatment of CD were included in the non-responder group.

Results

In total, 95 patients were included in the responder group and 45 patients were assigned to the non-responder group. Further, 48 (50.5%) of the 95 patients in the responder group had 6-TGN concentrations within optimal range (235–450 pmol/8x108 RBCs), and 8 (17.8%) of the 45 patients in the non-responder group had 6-TGN concentration in the optimal range (p-value < 0.001).

Table 1 Optimal 6-TGN concentrations of controlled group and uncontrolled group

SuboptimalOptimalOver
< 235235–450450P-value
Responder (n, %)30 (31.6%)48 (50.5%)17 (17.9%)< 0.001
Non-responder (n, %)36 (80.0%)8 (17.8%)1 (2.2%)

The odds ratio for having active status in case of inadequate 6-TGN value was 4.73 (CI 95%, 1.99–11.20). Mean 6-TGN levels were significantly different between the responder and non-responder groups, at 338.6 vs 173.8 pmol/8 × 108 erythrocytes, respectively (p < 0.001).

Table 2 Results of thiopurine metabolites levels

Total (n = 140)Responder (n = 95)Non-responder (n = 45)p-value
Mean 6-TGN285.6 ± 202.9338.6 ± 215.2173.8 ± 110.6< 0.001
Mean 6-MMP575.1 ± 644.4593.2 ± 611.6536.8 ± 714.40.63

Level of 6-TGN showed a significant correlation with thiopurine dose (r = 0.357; p < 0.001), but was not associated with mean corpuscular volume (r = 0.152; p = 0.072) and white blood cell (WBC) count (r = -0.058, p = 0.496). Moreover, there was a trend for correlation between CDAI score and 6-TGN level, but it did not reach statistical significance(r = -0.163, p = 0.055).

Conclusion

The 6-TGN levels within adequate therapeutic range are associated with a significantly higher chance of being in remission status. The monitoring of 6-TGN concentration may be helpful in the management of CD in adult Korean patients.

References

[1] Cuffari C, Dassopoulos T, Turnbough L, et al. Thiopurine methyltransferase activity influences clinical response to azathioprine in inflammatory bowel disease. Clin Gastroenterol Hepatol 2004;2(5):410–17.

[2] Kwan LY, Devlinb SM, Mirocha JM, et al. Thiopurine methyltransferase activity combined with 6-thioguanine metabolite levels predicts clinical response to thiopurines in patients with inflammatory bowel disease. Dig Liver Dis 2008;40(6):425–32.

[3] Andoh A, Tsujikawa T, Ban H, et al. Monitoring 6-thioguanine nucleotide concentrations in Japanese patients with inflammatory bowel disease. J Gastroenterol Hepatology 2008;23(9):1373–77.

[4] Haines ML, Ajlouni Y, Irving PM, et al. Clinical usefulness of therapeutic drug monitoring of thiopurines in patients with inadequately controlled inflammatory bowel disease. Inflamm Bowel Dis 2011;17(6):1301–07.

[5] Lee MN, Kang B, Choi SY, et al. Impact of genetic polymorphisms on 6-thioguanine nucleotide levels and toxicity in pediatric patients with IBD treated with azathioprine. Inflamm Bowel Dis 2015;21(12):2897–908.