{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T14:04:58Z","timestamp":1784729098962,"version":"3.55.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Methotrexate has demonstrated efficacy in Crohn\u2019s disease (CD) as monotherapy and is increasingly used in combination therapy. We investigated for the first time the use of methotrexate in a very large cohort of patients with inflammatory bowel disease (IBD) in a real-world setting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This was an observational, retrospective, multicenter study including consecutive adult IBD patients treated with methotrexate in monotherapy or combination therapy between January 2015 and December 2022 in 15 French centers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among the 1115 patients included, 77% had CD and 34.5% had at least one extra-intestinal manifestation (EIM). Regarding prior treatments, 44.0% of patients had been exposed to azathioprine and 75.1% to anti-tumor necrosis factor agents. The primary indication for methotrexate was IBD (81.5%), followed by EIM (rheumatological [11.9%] or dermatological [3.9%]). Methotrexate was prescribed in combination therapy in 90.6% of cases. The most frequent induction and maintenance dose was 15\u2009mg\/week (47.5% and 51.1% respectively). The persistence rate of methotrexate was 27.7\u2009months in CD and 22.4\u2009months in ulcerative colitis (UC). For CD, factors associated with persistence were female gender (hazard ratio [HR] 1.26; 95% confidence interval [CI] 1.05-1.51) and the presence of EIM (HR 0.71; 95% CI 0.58-0.86), and for UC, the presence of EIM (HR 0.63; 95% CI 0.42-0.94). Among the 344 (31.7%) patients who experienced an adverse event related to methotrexate, nine experienced a serious adverse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The French multicenter MICI-METHO study is the first to provide a comprehensive overview of the real-world use, persistence, and safety of methotrexate in patients with IBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjag102","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:32:59Z","timestamp":1784727179000},"source":"Crossref","is-referenced-by-count":0,"title":["Methotrexate for inflammatory bowel disease: the MICI-METHO multicenter retrospective cohort study"],"prefix":"10.1093","volume":"20","author":[{"given":"B\u00e9n\u00e9dicte","family":"Caron","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Nancy University Hospital, and INSERM, NGERE, University of Lorraine , Nancy F-54000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2314-9284","authenticated-orcid":false,"given":"Julien","family":"Kirchgesner","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, H\u00f4pital Saint-Antoine, AP-HP, Sorbonne Universit\u00e9, INSERM, FHU GLIMMER, Institut Pierre Louis d\u2018Epid\u00e9miologie et de Sant\u00e9 Publique , Paris, F-75012,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Nachury","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE\u2014Institute for Translational Research in Inflammation , Lille F-59000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Bouguen","sequence":"additional","affiliation":[{"name":"CHU Rennes, Universit\u00e9 Rennes, INSERM, CIC1414, Institut NUMECAN (Nutrition Metabolism and Cancer) , Rennes F-35000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-2879","authenticated-orcid":false,"given":"Mathieu","family":"Uzzan","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, APHP, Mondor Hospital , Cr\u00e9teil,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-409X","authenticated-orcid":false,"given":"Anthony","family":"Buisson","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Clermont Auvergne, Inserm, CHU Clermont-Ferrand, 3iHP, Service d\u2018H\u00e9pato-Gastro Ent\u00e9rologie , Clermont-Ferrand,","place":["France"]},{"name":"Universit\u00e9 Clermont Auvergne, 3iHP, Inserm U1071, M2iSH, USC-INRA 2018 , Clermont-Ferrand,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8416-5432","authenticated-orcid":false,"given":"Guillaume","family":"Le Cosquer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Pancreatology, H\u00f4pital Rangueil, CHU de Toulouse, Universit\u00e9 Toulouse Paul Sabatier , Toulouse,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9845-6572","authenticated-orcid":false,"given":"Lucine","family":"Vuitton","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Hospital of Besan\u00e7on and UMR 1098 Right INSERM, EFS Bourgogne-Franche-Comt\u00e9 and University of Franche-Comt\u00e9 , Besan\u00e7on,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Seksik","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, H\u00f4pital Saint-Antoine, FHU GLIMMER, Centre de Recherche Saint-Antoine, INSERM, AP-HP, Sorbonne Universit\u00e9 , Paris,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Petit","sequence":"additional","affiliation":[{"name":"MICI Platform, Nancy Unveristy Hospital , Nancy F-54000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Wils","sequence":"additional","affiliation":[{"name":"Univ. Lille, Inserm, CHU Lille, U1286-INFINITE-Institute for Translational Research in Inflammation , Lille, Hauts-de-France,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Nancey","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Lyon-Sud Hospital, Hospices Civils de Lyon, and INSERM U1111, CIRI, University Lyon1 , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romain","family":"Altwegg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Montpellier Hospital, CHU St Eloi , Montpellier,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5158-2321","authenticated-orcid":false,"given":"Marianne","family":"Hupe","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes\/Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes\/Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209 , Grenoble 38043,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathurin","family":"Fumery","sequence":"additional","affiliation":[{"name":"Gastroenterology Department, Amiens University Hospital and PeriTox, Universit\u00e9 de Picardie Jules Verne , Amiens,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Roblin","sequence":"additional","affiliation":[{"name":"Service gastroent\u00e9rologie, CHU Saint Etienne , Saint Etienne,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Laharie","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9pato-gastroent\u00e9rologie et oncologie digestive, CHU de Bordeaux, H\u00f4pital Haut-L\u00e9v\u00eaque, Universit\u00e9 de Bordeaux , Bordeaux F-33000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Hebuterne","sequence":"additional","affiliation":[{"name":"Gastroenterology and Clinical Nutrition, University C\u00f4te d\u2019Azur , Nice,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9dric","family":"Baumann","sequence":"additional","affiliation":[{"name":"Methodology, Data Management and Statistics Unit, University Hospital of Nancy , Nancy 54000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Vicaut","sequence":"additional","affiliation":[{"name":"Clinical Trial Unit, Hospital Lariboisi\u00e8re APHP , Paris 75010,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2536-6618","authenticated-orcid":false,"given":"Laurent","family":"Peyrin-Biroulet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Nancy University Hospital, and INSERM, NGERE, University of Lorraine , Nancy F-54000,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"2026072209325190700_jjag102-B1","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1111\/apt.18194","article-title":"Systematic review: methotrexate-A poorly understood and underused medication in inflammatory bowel disease","volume":"60","author":"Sequier","year":"2024","journal-title":"Aliment Pharmacol Ther"},{"key":"2026072209325190700_jjag102-B2","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1056\/NEJM199502023320503","article-title":"Methotrexate for the treatment of Crohn\u2019s disease. The North American Crohn\u2019s Study Group Investigators","volume":"332","author":"Feagan","year":"1995","journal-title":"N Engl J Med"},{"key":"2026072209325190700_jjag102-B3","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1097\/00042737-200012110-00010","article-title":"6-Mercaptopurine or methotrexate added to prednisone induces and maintains remission in steroid-dependent inflammatory bowel disease","volume":"12","author":"Mat\u00e9-Jim\u00e9nez","year":"2000","journal-title":"Eur J Gastroenterol Hepatol"},{"key":"2026072209325190700_jjag102-B4","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1080\/17474124.2019.1596797","article-title":"Methotrexate for inflammatory bowel disease: time for reconsideration","volume":"13","author":"Nielsen","year":"2019","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"2026072209325190700_jjag102-B5","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1093\/ecco-jcc\/jjab178","article-title":"ECCO guidelines on therapeutics in ulcerative colitis: medical treatment","volume":"16","author":"Raine","year":"2022","journal-title":"J Crohns Colitis"},{"key":"2026072209325190700_jjag102-B6","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1016\/s1590-8658(03)00372-4","article-title":"Comparison between methotrexate and azathioprine in the treatment of chronic active Crohn\u2019s disease: a randomised, investigator-blind study","volume":"35","author":"Ardizzone","year":"2003","journal-title":"Dig Liver Dis."},{"key":"2026072209325190700_jjag102-B7","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1080\/14740338.2016.1218468","article-title":"Safety profile of methotrexate in inflammatory bowel disease","volume":"15","author":"Gabbani","year":"2016","journal-title":"Expert Opin Drug Saf"},{"key":"2026072209325190700_jjag102-B8","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1016\/S0140-6736(09)61302-7","article-title":"Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study","volume":"374","author":"Beaugerie","year":"2009","journal-title":"Lancet."},{"key":"2026072209325190700_jjag102-B9","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1093\/ecco-jcc\/jjz180","article-title":"ECCO guidelines on therapeutics in Crohn\u2019s disease: medical treatment","volume":"14","author":"Torres","year":"2020","journal-title":"J Crohns Colitis"},{"key":"2026072209325190700_jjag102-B10","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1093\/ecco-jcc\/jjv027","article-title":"Optimal doses of methotrexate combined with anti-TNF therapy to maintain clinical remission in inflammatory bowel disease","volume":"9","author":"Colman","year":"2015","journal-title":"J Crohns Colitis"},{"key":"2026072209325190700_jjag102-B11","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s10620-023-08237-0","article-title":"Effectiveness and tolerability of methotrexate combined with biologics in patients with Crohn\u2019s disease: a multicenter observational study","volume":"69","author":"Park","year":"2024","journal-title":"Dig Dis Sci"},{"key":"2026072209325190700_jjag102-B12","doi-asserted-by":"publisher","first-page":"4382","DOI":"10.3390\/jcm12134382","article-title":"The role of low-dose oral methotrexate in increasing anti-TNF drug levels and reducing immunogenicity in IBD","volume":"12","author":"Demase","year":"2023","journal-title":"J Clin Med"},{"key":"2026072209325190700_jjag102-B13","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1056\/NEJM200006013422202","article-title":"A comparison of methotrexate with placebo for the maintenance of remission in Crohn\u2019s disease. North American Crohn\u2019s Study Group Investigators","volume":"342","author":"Feagan","year":"2000","journal-title":"N Engl J Med"},{"key":"2026072209325190700_jjag102-B14","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/apt.12161","article-title":"Pharmacokinetic profiles for oral and subcutaneous methotrexate in patients with Crohn\u2019s disease","volume":"37","author":"Wilson","year":"2013","journal-title":"Aliment Pharmacol Ther"},{"key":"2026072209325190700_jjag102-B15","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1046\/j.1365-2036.2003.01614.x","article-title":"Bioavailability of oral vs. subcutaneous low-dose methotrexate in patients with Crohn\u2019s disease","volume":"18","author":"Kurnik","year":"2003","journal-title":"Aliment Pharmacol Ther"},{"key":"2026072209325190700_jjag102-B16","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1007\/s11926-023-01116-7","article-title":"Oral versus subcutaneous methotrexate in immune-mediated inflammatory disorders: an update of the current literature","volume":"25","author":"Vermeer","year":"2023","journal-title":"Curr Rheumatol Rep"},{"key":"2026072209325190700_jjag102-B17","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1053\/j.gastro.2021.07.042","article-title":"Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management","volume":"161","author":"Rogler","year":"2021","journal-title":"Gastroenterology"},{"key":"2026072209325190700_jjag102-B18","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1111\/apt.16039","article-title":"Thiopurines vs methotrexate: Comparing tolerability and discontinuation rates in the treatment of inflammatory bowel disease","volume":"52","author":"Vasudevan","year":"2020","journal-title":"Aliment Pharmacol Ther"},{"key":"2026072209325190700_jjag102-B19","doi-asserted-by":"publisher","first-page":"17562848211043017","DOI":"10.1177\/17562848211043017","article-title":"Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn\u2019s disease: a retrospective study","volume":"14","author":"Hong","year":"2021","journal-title":"Ther Adv Gastroenterol"},{"key":"2026072209325190700_jjag102-B20","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1111\/j.1572-0241.2000.02190.x","article-title":"Methotrexate in Crohn\u2019s disease: long-term efficacy and toxicity","volume":"95","author":"L\u00e9mann","year":"2000","journal-title":"Am J Gastroenterol"},{"key":"2026072209325190700_jjag102-B21","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.jhep.2022.12.034","article-title":"Risk of liver fibrosis associated with long-term methotrexate therapy may be overestimated","volume":"78","author":"Atallah","year":"2023","journal-title":"J Hepatol"},{"key":"2026072209325190700_jjag102-B22","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/j.jhep.2023.02.018","article-title":"Methotrexate-induced liver fibrosis: the end of a long-held belief","volume":"78","author":"Di Martino","year":"2023","journal-title":"J Hepatol"},{"key":"2026072209325190700_jjag102-B23","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1056\/NEJMoa0904492","article-title":"Infliximab, azathioprine, or combination therapy for Crohn\u2019s disease","volume":"362","author":"Colombel","year":"2010","journal-title":"N Engl J Med"},{"key":"2026072209325190700_jjag102-B24","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1053\/j.gastro.2013.11.024","article-title":"Methotrexate in combination with infliximab is no more effective than infliximab alone in patients with Crohn\u2019s disease","volume":"146","author":"Feagan","year":"2014","journal-title":"Gastroenterology"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/7\/jjag102\/69784687\/jjag102.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/20\/7\/jjag102\/69784687\/jjag102.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:33:00Z","timestamp":1784727180000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/doi\/10.1093\/ecco-jcc\/jjag102\/8739761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":24,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7,7]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjag102","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,7]]},"published":{"date-parts":[[2026,7]]},"article-number":"jjag102"}}