{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:25:22Z","timestamp":1775715922414,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008359","name":"Maag Lever Darm Stichting","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008359","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":[[2023,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate\u2010polyglutamate (MTX\u2010PG) in erythrocytes might enable TDM for methotrexate in patients with Crohn's disease (CD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate the relationship between MTX\u2010PGs and methotrexate drug survival, efficacy and toxicity<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a multicentre prospective cohort study, patients with CD starting subcutaneous methotrexate without biologics were included and followed for 12\u2009months. Primary outcome was subcutaneous methotrexate discontinuation or requirement for step\u2010up therapy. Secondary outcomes included faecal calprotectin (FCP), Harvey Bradshaw Index (HBI), hepatotoxicity and gastrointestinal intolerance. Erythrocyte MTX\u2010PGs were analysed at weeks 8, 12, 24 and 52 or upon treatment discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We included 80 patients with CD (mean age 55\u2009\u00b1\u200913y, 35% male) with a median FCP of 268\u2009\u03bcg\/g (IQR 73\u2013480). After the 12\u2010month visit, 21 patients (26%) were still on subcutaneous methotrexate monotherapy. Twenty\u2010one patients stopped because of disease activity, 29 because of toxicity, and four for both reasons. Five patients ended study participation or stopped methotrexate for another reason. A higher MTX\u2010PG<jats:sub>3<\/jats:sub> concentration was associated with a higher rate of methotrexate drug survival (HR 0.86, 95% CI 0.75\u20130.99), lower FCP (<jats:italic>\u03b2<\/jats:italic> \u22123.7, SE 1.3, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and with biochemical response (FCP \u2264250 if baseline &gt;250\u2009\u03bcg\/g; OR 1.1, 95% CI 1.0\u20131.3). Higher MTX\u2010PGs were associated with less gastrointestinal intolerance. There was no robust association between MTX\u2010PGs and HBI or hepatotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Higher MTX\u2010PG<jats:sub>3<\/jats:sub> concentrations are related to better methotrexate drug survival and decreased FCP levels. Therefore, MTX\u2010PG<jats:sub>3<\/jats:sub> could be used for TDM if a target concentration can be established.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17719","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T11:07:50Z","timestamp":1695899270000},"page":"1151-1162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Therapeutic drug monitoring of methotrexate in patients with Crohn's disease"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2415-5114","authenticated-orcid":false,"given":"Maartje M.","family":"van de Meeberg","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam University Medical Centre, VU University Amsterdam  Amsterdam the Netherlands"},{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht, Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herma H.","family":"Fidder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht, Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bas","family":"Oldenburg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology University Medical Centre Utrecht, Utrecht University  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janani","family":"Sundaresan","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduard A.","family":"Struys","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nahid S. M.","family":"Montazeri","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, Department of Gastroenterology and Hepatology Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wout G. N.","family":"Mares","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Gelderse Vallei Hospital  Ede the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nofel","family":"Mahmmod","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology St. Antonius Hospital  Nieuwegein the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk P.","family":"van Asseldonk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology NWZ Alkmaar  Alkmaar the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurice W. M. D.","family":"Lutgens","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Elisabeth\u2010TweeSteden Hospital  Tilburg the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan P.","family":"Kuyvenhoven","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Spaarne Gasthuis  Haarlem the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svend T.","family":"Rietdijk","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology OLVG  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loes H. C.","family":"Nissen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Jeroen Bosch Hospital  's\u2010Hertogenbosch the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parweez","family":"Koehestanie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Bravis Hospital  Roosendaal the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanne K. H.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam University Medical Centre, VU University Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Bouma","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam University Medical Centre, VU University Amsterdam  Amsterdam the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maja","family":"Bulatovi\u0107\u00a0\u0106alasan","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry Amsterdam UMC  Amsterdam the Netherlands"},{"name":"Department of Rheumatology and Clinical Immunology University Medical Centre Utrecht  Utrecht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the Dutch Initiative on Crohn and Colitis (ICC)","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200006013422202"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2020.100271"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/17562848221085889"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjz180"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11938\u2010017\u20100128\u20100"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco\u2010jcc\/jjab050"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.06.018"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2019.1597054"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/BCP.15579"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2016.06.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.175"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216\u2010012\u20106581\u20107"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00177"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010022\u201002439\u2010y"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis\u20102013\u2010203725"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1749\u20104486.2008.01668.X"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000853"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1159\/000201455"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph13121236"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2015.06.001"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30367"},{"key":"e_1_2_10_23_1","unstructured":"R foundation for statistical computing. 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