{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:06:59Z","timestamp":1791313619780,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003061","name":"Erasmus Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Low\u2010dose thiopurine\u2010allopurinol (LDTA) combination therapy is a commonly applied optimisation strategy in IBD patients with a skewed thiopurine metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To assess continued LDTA maintenance treatment at annual intervals and explore risk factors for treatment cessation<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult IBD patients treated with LDTA between 2009 and 2016 were retrospectively included. Data on the incidence of clinical and laboratory adverse events (AEs), including hepatotoxicity and myelotoxicity resulting in imposing LDTA therapy cessation and associated risk factors were collected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, 221 IBD patients (46% male, median age 42\u00a0years) were included. Maintenance LDTA treatment was continued in 78%\u00a0of patients at 1\u00a0year (n\u00a0=\u00a0145), 66% at 2\u00a0years (n\u00a0=\u00a083), 57% at 3\u00a0years (n\u00a0=\u00a052) and 52% at 4\u00a0years (n\u00a0=\u00a033). Treatment in patients receiving LDTA therapy for AEs during thiopurine monotherapy was more often continued than in patients initiating LDTA for other indications (eg, ineffectiveness of thiopurine monotherapy, routinely discovered skewed metabolism) (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.016). Myelotoxicity during thiopurine monotherapy resolved in 87% and hepatotoxicity in 86% after median of 1.2 and 1.4\u00a0months after LDTA initiation. Cumulative incidence of AEs during LDTA resulting in therapy cessation within total follow\u2010up of 449 treatment\u2010years was 7% for clinical AEs, 4% for myelotoxicity and 1% for hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LDTA therapy is a safe and beneficial optimisation strategy in IBD patients. Continued maintenance LDTA treatment is 52% after 4\u00a0years of treatment and most commonly affected by ineffectiveness of LDTA rather than LDTA\u2010attributed toxicity. LDTA optimisation strategy is most advantageous in patients failing thiopurine monotherapy due to AEs.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.15402","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T07:58:56Z","timestamp":1564473536000},"page":"407-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Real\u2010life study of safety of thiopurine\u2010allopurinol combination therapy in inflammatory bowel disease: myelotoxicity and hepatotoxicity rarely affect maintenance treatment"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4015-5571","authenticated-orcid":false,"given":"Joany E.","family":"Kreijne","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-0931","authenticated-orcid":false,"given":"Rozanne C.","family":"de Veer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanne K.","family":"de Boer","sequence":"additional","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":"Gerard","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Center Groningen and University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"West","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Sint Franciscus Gasthuis &amp; Vlietland Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1947-8971","authenticated-orcid":false,"given":"Sofia A. W.","family":"Moorsel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Zuyderland Medical Center Heerlen\u2010Sittard\u2010Geleen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk J.","family":"de Jong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Radboud University Medical Center Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Janneke","family":"van der Woude","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemarie C.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"of the Dutch Initiative on Crohn, Colitis (ICC)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70140-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200208000-00003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.4.485"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-8-641"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.8.1081"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01187.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2006.02977.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.06.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13656"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e328334338f"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210790112773"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000213"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2012.12.006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2008.03782.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.06.002"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2006.11.020"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365521.2016.1216589"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2012.02.007"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000827"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2005.02583.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.23021"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2018.02.001"},{"key":"e_1_2_7_24_1","first-page":"87","article-title":"Xanthine oxidase: biochemistry, distribution and physiology","volume":"548","author":"Parks DA","year":"1986","journal-title":"Acta Physiol Scand Suppl"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.58"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(90)90124-A"},{"key":"e_1_2_7_27_1","first-page":"423","article-title":"A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6\u2010mercaptopurine, cyclosporine, and methotrexate","volume":"91","author":"Sandborn WJ","year":"1996","journal-title":"Am J Gastroenterol"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X17733657"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0904492"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.crohns.2010.02.009"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001163"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04221.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14571"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1373\/49.2.260"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257770.2011.597371"}],"container-title":["Alimentary Pharmacology &amp; 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