Title: | Early Assessment of Thiopurine Metabolites Identifies Patients at Risk of Thiopurine-induced Leukopenia in Inflammatory Bowel Disease |
Author(s): | Wong, D.R.; Coenen, M.J.H. ; Vermeulen, S.H. ; Derijks, L.J.; Marrewijk, C.J. van ; Klungel, O.H.; Scheffer, H. ; Franke, B. ; Guchelaar (LUMC), H.J.; Jong, D.J. de ; Engels, L.G.; Verbeek, A.L.M. ; Hooymans, P.M. |
Publication year: | 2017 |
Source: | Journal of Crohn's and Colitis, vol. 11, iss. 2, (2017), pp. 175-184 |
ISSN: | 1873-9946 |
DOI: | https://doi.org/10.1093/ecco-jcc/jjw130 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/169964 ![]() |
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Subject: | Radboudumc 0: Other Research RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 15: Urological cancers RIHS: Radboud Institute for Health Sciences Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience Radboudumc 5: Inflammatory diseases RIHS: Radboud Institute for Health Sciences Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience |
Organization: | Human Genetics Health Evidence Haematology Psychiatry Radboudumc Extern Gastroenterology |
Journal title: |
Journal of Crohn's and Colitis
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Volume: | vol. 11 |
Issue: | iss. 2 |
Page start: | p. 175 |
Page end: | p. 184 |
Abstract: |
BACKGROUND AND AIMS: Only a quarter of thiopurine-induced myelotoxicity in inflammatory bowel disease [IBD] patients is related to thiopurine S-methyltransferase deficiency. We determined the predictive value of 6-thioguanine nucleotide [6-TGN] and 6-methylmercaptopurine ribonucleotide [6-MMPR] concentrations 1 week after initiation [T1] for development of leukopenia during the first 8 weeks of thiopurine treatment. METHODS: The study was performed in IBD patients starting thiopurine therapy as part of the Dutch randomized controlled TOPIC trial [ClinicalTrials.gov NCT00521950]. Blood samples for metabolite measurement were collected at T1. Leukopenia was defined by leukocyte counts of <3.0 x 109/L. For comparison, patients without leukopenia who completed the 8 weeks on the stable dose were selected from the first 272 patients of the TOPIC trial. RESULTS: Thirty-two patients with, and 162 patients without leukopenia were analysed. T1 threshold 6-TGN concentrations of 213 pmol/8 x 108 erythrocytes and 3525 pmol/8 x 108 erythrocytes for 6-MMPR were defined: patients exceeding these values were at increased leukopenia risk (odds ratio [OR] 6.2 [95% CI: 2.8-13.8] and 5.9 [95% CI: 2.7-13.3], respectively). Leukopenia rates were higher in patients treated with mercaptopurine, compared with azathioprine (OR 7.3 [95% CI: 3.1-17.0]), and concurrent anti-TNF therapy (OR 5.1 [95% CI: 1.6-16.4]). Logistic regression analysis of thiopurine type, threshold concentrations, and concurrent anti-tumour necrosis factor [TNF] therapy revealed that elevations of both T1 6-TGN and 6-MMPR resulted in the highest risk for leukopenia, followed by exceeding only the T1 6-MMPR or 6-TGN threshold concentration (area under the curve 0.84 [95% CI: 0.76-0.92]). CONCLUSIONS: In ~80% of patients, leukopenia could be explained by T1 6-TGN and/or 6-MMPR elevations. Validation of the predictive model is needed before implementing in clinical practice.
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