Rac1/ pSTAT3 expression: A pharmacodynamic marker panel as a first step toward optimization of thiopurine therapy in inflammatory bowel disease patients

2021 ◽  
Author(s):  
Debbie S. Deben ◽  
Arjan J. Adrichem ◽  
Roosmarie Drent ◽  
Sabine Puts ◽  
Kelly E. J. M. Pelzer ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Marker Panel ◽  
Pharmacodynamic Marker ◽  
Thiopurine Therapy ◽  
Inflammatory Bowel

Rac1 as a Potential Pharmacodynamic Biomarker for Thiopurine Therapy in Inflammatory Bowel Disease

2016 ◽  
Vol 38 (5) ◽  
pp. 621-627 ◽  
Author(s):  
Margien L. Seinen ◽  
Geerten P. van Nieuw Amerongen ◽  
Nanne K. H. de Boer ◽  
Chris J. J. Mulder ◽  
Jan van Bezu ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Thiopurine Therapy ◽  
Inflammatory Bowel

Safety of Thiopurine Therapy in Inflammatory Bowel Disease

2013 ◽  
Vol 19 (7) ◽  
pp. 1404-1410 ◽  
Author(s):  
María Chaparro ◽  
Ingrid Ordás ◽  
Eduard Cabré ◽  
Valle Garcia-Sanchez ◽  
Guillermo Bastida ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Thiopurine Therapy ◽  
Inflammatory Bowel

scholarly journals A practical guide to thiopurine prescribing and monitoring in IBD

2016 ◽  
Vol 9 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Ben Warner ◽  
Emma Johnston ◽  
Monica Arenas-Hernandez ◽  
Anthony Marinaki ◽  
Peter Irving ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Clinical Practice ◽  
Bowel Disease ◽  
Practical Guide ◽  
Thiopurine Therapy ◽  
Thioguanine Nucleotide ◽  
Inflammatory Bowel

Thiopurines are often the mainstay of treatment for many patients with inflammatory bowel disease. As such, a general understanding of the evidence behind their use and of their metabolism is extremely useful in clinical practice. This review gives a practical overview of thiopurine metabolism, the importance of thiopurine S-methyltransferase testing prior to the start of therapy and the monitoring of thioguanine nucleotide levels while on treatment, guiding a personalised approach to optimising thiopurine therapy.

scholarly journals P339 Assessment of DNA-thioguanine nucleotide identifies patients at risk of thiopurine-induced leukopoenia in inflammatory bowel disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S325-S326
Author(s):  
X Zhu ◽  
K Chao ◽  
X Gao ◽  
M Huang ◽  
X D Wang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Roc Curves ◽  
Blood Samples ◽  
Clinical Toxicity ◽  
Thiopurine Therapy ◽  
Thioguanine Nucleotide ◽  
Patients At Risk ◽  
Inflammatory Bowel ◽  
The Impact

Abstract 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 (p = 0.050). However, there was a significant association between DNA-TGN levels and TIL. Patients who developed TIL were identified with a higher DNA-TGN levels compared with those who did not (p = 0.00030, 456.9 (63.3–879.2) vs. 268.9 (45.6–916.8) fmol/μg DNA). The area under the ROC curves of the continuous DNA-TGN concentration to predict TIL was 0.75 (95% CI: 0.63~0.87) and almost 84% (16/19) of the TIL could be explained based on the DNA-TGN cut-off value of 343.9 fmol/μg DNA 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.

Thiopurine therapy in inflammatory bowel disease patients: Analyses of two 8-year intercept cohorts

2010 ◽  
Vol 16 (9) ◽  
pp. 1541-1549 ◽  
Author(s):  
B. Jharap ◽  
M. L. Seinen ◽  
N. K.H. de Boer ◽  
J. R. van Ginkel ◽  
R. K. Linskens ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Thiopurine Therapy ◽  
Inflammatory Bowel
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