{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T15:44:59Z","timestamp":1757778299002,"version":"3.40.5"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,25]],"date-time":"2024-08-25T00:00:00Z","timestamp":1724544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Conventional thiopurines (azathioprine and mercaptopurine) remain standard therapy to maintain steroid sparing remission in inflammatory bowel disease (IBD), but are regularly discontinued due to adverse drug reactions (ADRs). Measurement of the metabolites 6\u2010thioguanine nucleotides (6\u2010TGN), 6\u2010methylmercaptopurine ribonucleotides (6\u2010MMPR) and the 6\u2010MMPR\/6\u2010TGN ratio, may predict the development of these ADRs. Our aim was to evaluate whether early thiopurine metabolite measurements were associated with clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A post\u2010hoc analysis was conducted of a multicentre, prospective, observational study on thiopurine\u2010induced hepatotoxicity. IBD patients who initiated thiopurine therapy were included and thiopurine metabolite concentrations were assessed after 7\u00a0days (\u00b11) (T1). Patients were monitored for 12\u2009weeks to document the occurrence of ADRs, early treatment discontinuation and effectiveness.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 181 patients were evaluated. At T1, 6\u2010MMPR concentrations and 6\u2010TGN\/6\u2010MMPR ratios were independently related to treatment discontinuation within 12\u2009weeks after correction for sex, age and body mass index (BMI) (<jats:italic>P<\/jats:italic>\u00a0=\u2009.034 and .002, respectively). The largest effects were observed for 6\u2010MMPR \u22653000\u00a0pmol\/8\u2009\u00d7\u200910<jats:sup>8<\/jats:sup> RBC and 6\u2010TGN\/6\u2010MMPR ratio \u226517. Furthermore, 6\u2010MMPR concentrations and 6\u2010TGN\/6\u2010MMPR ratios at T1 were independently related to skewed metabolism at steady state (Week 8, 6\u2010MMPR\/\u20106TGN ratio \u226511 and \u226520) (both <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.001). The occurrence of ADRs and effectiveness were not independently related to T1 thiopurine metabolite concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Thiopurine metabolite concentrations at T1 were related to early treatment discontinuation and skewed metabolism at steady state, but not to effectiveness, helping to identify patients with a high risk of thiopurine treatment failure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16219","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T06:04:50Z","timestamp":1724652290000},"page":"3296-3307","source":"Crossref","is-referenced-by-count":1,"title":["Early therapeutic drug monitoring helps to identify inflammatory bowel disease patients with a high risk to fail thiopurine treatment"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2956-5713","authenticated-orcid":false,"given":"Debbie S.","family":"Deben","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Clinical Pharmacology and Toxicology Zuyderland Medical Centre  Sittard\u2010Geleen\/Heerlen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bjorn","family":"Winkens","sequence":"additional","affiliation":[{"name":"Department of methodology and statistics, CAPHRI Care and Public Health Research Institute Maastricht University Medical Center  Maastricht Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia A. W.","family":"van Moorsel","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Jeroen Bosch Hospital  \u2018s\u2010Hertogenbosch Netherlands"},{"name":"Department of Clinical Pharmacy Bernhoven Hospital  Uden Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brigit P. 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G.","family":"Leers","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Hematology Zuyderland Medical Centre  Sittard\u2010Geleen\/Heerlen Netherlands"},{"name":"Faculty of Science Open Universiteit  Heerlen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis R.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Clinical Pharmacology and Toxicology Zuyderland Medical Centre  Sittard\u2010Geleen\/Heerlen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriaan A.","family":"van Bodegraven","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Maastricht University Medical Center  Maastricht Netherlands"},{"name":"Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co\u2010MIK) Zuyderland Medical Centre  Sittard\u2010Geleen\/Heerlen Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,25]]},"reference":[{"issue":"1491","key":"e_1_2_9_2_1","first-page":"46","article-title":"New Zealand Society of Gastroenterology guidelines on therapeutic drug monitoring in inflammatory bowel disease","volume":"132","author":"Khan A","year":"2019","journal-title":"N Z Med J"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjab178"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjz180"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17128"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21221"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjad022"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.11.039"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102832"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izx065"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12664\u2010024\u201001529\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(22)00385\u20105"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI16432"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13879"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000414"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4292\/wjgpt.v7.i4.524"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620\u2010019\u201005720\u20105"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001163"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.39.3.401"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2428"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2021.2029406"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691\u2010200406000\u201000016"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.32420"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000213"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102036.2012.05084.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000001031"},{"key":"e_1_2_9_27_1","unstructured":"Werkgroep Modernisering Richtlijn IBD.Handleiding behandeling IBD 2014\u20132015. 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