P339 Assessment of DNA-thioguanine nucleotide identifies patients at risk of thiopurine-induced leukopoenia in inflammatory bowel disease
X. Zhu1, K. Chao2, X. Gao2, M. Huang1, X.D. Wang1
1School of Pharmaceutical Sciences, Sun Yat-Sen Unversity, Guangzhou, China, 2Department of Gastroenterology, the Sixth Affiliated Hospital- Sun Yat-sen University, Guangzhou, China
Background
Thiopurine drugs plays an important role for immunosuppressive therapy in inflammatory bowel disease. The molecular mechanism of the thiopurine toxicity is primarily mediated by DNA-incorporated thioguanine nucleotides (DNA-TGN). The aim of this study was to assess the impact of DNA-TGN levels on thiopurine-induced toxicity.
Methods
Patients over 18 years who were diagnosed with IBD and prescribed on thiopurines from February 2019 to August 2019 were recruited. All of them were genotyped with NUDT15 R139C before the thiopurine therapy. A novel assay was established to measure levels of DNA-TGN in blood leucocytes. The DNA-TGN and 6TGN levels were correlated with clinical toxicity.
Results
185 patients with Crohn’s disease and 5 patients with ulcerative colitis were included in this study. DNA-TGN and 6TGN levels could be quantified in 229 patients’ blood samples. Thiopurine-induced leukopoenia (TIL) arose in 19 individuals with the median 6TGN level of 308.0 pmol/8×108 RBC which was not significantly different from the patients without TIL (
Conclusion
This study shows that quantification of DNA-TGN levels can be applied to gauge thioprine therapy and avoid TIL after pre-genotyping NUDT15 R139C in inflammatory bowel disease patients.