{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:34:47Z","timestamp":1773264887605,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007949","name":"Reumatikerf\u00f6rbundet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007949","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007857","name":"Stiftelsen Konung Gustaf V:s 80-\u00e5rsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007857","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009800","name":"Stiftelsen Professor Nanna Svartz Fond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009800","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001858","name":"Vinnova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Methotrexate (MTX) is the mainstay initial treatment of rheumatoid arthritis (RA), but individual response varies and remains difficult to predict. The role of genetics remains unclear, but studies suggest its importance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Incident RA patients starting MTX\u2010monotherapy were identified through a large\u2010scale Swedish register linkage. Demographic, clinical, medical, and drug history features were combined with fully imputed genotype data and used to train and evaluate multiple learning models to predict key MTX treatment outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 2432 patients, we consistently observed an estimated area under the curve (AUC) of \u223c0.62, outperforming models trained on sex and age. The best performance was observed for EULAR primary response (AUC\u00a0=\u00a00.67), whereas models struggled the most with predicting discontinuation. Genetics provided negligible improvements to prediction quality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Despite an extensive study population with broad multi\u2010modal data, predicting MTX treatment outcomes remains a challenge. Common genetic variants added minimal predictive power over clinical features.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.20087","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T06:54:30Z","timestamp":1744008870000},"page":"693-701","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Common genetic variants do not impact clinical prediction of methotrexate treatment outcomes in early rheumatoid arthritis"],"prefix":"10.1111","volume":"297","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3221-7979","authenticated-orcid":false,"given":"Anton \u00d6berg","family":"Sysojev","sequence":"first","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9n\u00e9dicte","family":"Delcoigne","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Frisell","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Alfredsson","sequence":"additional","affiliation":[{"name":"Institute of Environmental Medicine (IMM) Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9601-6186","authenticated-orcid":false,"given":"Lars","family":"Klareskog","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Center for Molecular Medicine Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The SRQ biobank group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saedis","family":"Saevarsdottir","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"},{"name":"Faculty of Medicine School of Health Sciences University of Iceland  Reykjavik Iceland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Boman","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"},{"name":"MedTechLabs BioClinicum Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonid","family":"Padyukov","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Medicine Solna Karolinska Institutet and Karolinska University Hospital  Stockholm Sweden"},{"name":"Center for Molecular Medicine Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Askling","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"},{"name":"Rheumatology, Theme Infection and Inflammation Karolinska University Hospital  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3380-5342","authenticated-orcid":false,"given":"Helga","family":"Westerlind","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet  Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223356"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2023-003027"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22159"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-022-02851-5"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac645"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2023.111239"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11010044"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103800"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac032"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.24834"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11266"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-022-02873-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead301"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2023-003714"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e3181c30fb2"},{"key":"e_1_2_10_18_1","unstructured":"LundbergSM LeeSL.A unified approach to interpreting model predictions. InProc 31st Int Conf Neural Information Processing Systems.Long Beach CA:Curran Associates Inc.;2017. p.4768\u20134777."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.7992"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-205094"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2023.1146353"}],"container-title":["Journal of Internal Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/joim.20087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T16:49:49Z","timestamp":1747673389000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/joim.20087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,6]]},"references-count":20,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/joim.20087"],"URL":"https:\/\/doi.org\/10.1111\/joim.20087","archive":["Portico"],"relation":{},"ISSN":["0954-6820","1365-2796"],"issn-type":[{"value":"0954-6820","type":"print"},{"value":"1365-2796","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,6]]},"assertion":[{"value":"2025-04-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}