{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:02:54Z","timestamp":1790114574071,"version":"4.0.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T00:00:00Z","timestamp":1557964800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tioguanine (or thioguanine) is an alternative drug for IBD patients who fail prior conventional immunomodulating therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To report effectiveness, safety and therapeutic drug monitoring in a cohort of patients with prolonged tioguanine maintenance therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this nationwide, multicentre study, medical records of tioguanine\u2010 using IBD patients were retrospectively reviewed. Response to therapy was defined as clinical effectiveness without (re)initiation of corticosteroids, concurrent biological therapy or surgical intervention. All adverse events that occurred during the follow\u2010up were listed and graded according to the common terminology criteria (CTC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two hundred and seventy\u2010four patients (female 63%, Crohn's disease in 68%) were included with median treatment duration of 51\u00a0months, 1567 patient\u2010years of follow\u2010up and median 20\u00a0mg\/d tioguanine dosage. Tioguanine was tolerated in 79%, clinical effectiveness at 6\u00a0months was documented in 66% and sustained clinical effectiveness during 12\u00a0months in 51% of patients. Forty\u2010one per cent of patients developed adverse events: 5% were graded as severe. Adverse events comprised infection requiring hospitalisation in three and skin cancer in eight patients (two melanomas). Asymptomatic nodular regenerative hyperplasia of the liver occurred in two out of 52 patients with liver biopsies (3.8%) and portal hypertension in three whereof one potentially associated with tioguanine (0.4%). Clinical effectiveness was correlated with 6\u2010thioguanine nucleotide threshold concentrations &gt;682\u00a0pmol\/8\u00d710<jats:sup>8 <\/jats:sup>RBC (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Long\u2010term tioguanine therapy for at least 12\u00a0months was effective in 51% and well tolerated as a maintenance treatment for IBD in about 70% of patients. Adverse events were common, but mainly mild or moderate. 6\u2010Thioguanine nucleotide threshold concentration\u00a0\u2265\u00a0700\u00a0pmol\/8\u00d710<jats:sup>8 <\/jats:sup>RBC is proposed as target level with higher odds for clinical effectiveness.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15280","type":"journal-article","created":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T07:39:51Z","timestamp":1557992391000},"page":"54-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Sustained effectiveness, safety and therapeutic drug monitoring of tioguanine in a cohort of 274 IBD patients intolerant for conventional therapies"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8827-955X","authenticated-orcid":false,"given":"Melek","family":"Simsek","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam UMC, Vrije Universiteit Amsterdam, AG&amp;M Research Institute Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie S.","family":"Deben","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Clinical Pharmacology and Toxicology, Zuyderland Medical Centre Sittard\u2010Geleen\u2010Heerlen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen S.","family":"Horjus","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie V.","family":"B\u00e9nard","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit I.","family":"Lissenberg\u2010Witte","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J. C.","family":"Buiter","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"van Luin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy Rijnstate Hospital Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margien L.","family":"Seinen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam UMC, Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris J. 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