{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:39:15Z","timestamp":1794440355073,"version":"4.9.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100019559","name":"Carl von Ossietzky Universit\u00e4t Oldenburg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019559","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>Methotrexate (MTX), a standard treatment for rheumatoid arthritis (RA), is known for its potential kidney and liver toxicity. Whether concomitant use of analgesics, possibly affecting the same organs, has an impact on the occurrence or course of adverse drug reactions (ADRs) remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We used all spontaneous reports (until 2022) of suspected ADRs associated with MTX in RA patients, from the EudraVigilance database, a spontaneous report system operated by the European Medicines Agency (EMA). We displayed case and treatment characteristics, stratified by the organ affected (kidneys, liver) and the outcome (fatal, non-fatal).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We included a total of 10,319 reports (mean age: 62.3 years, 72.6% female). 365 and 1,082 were related to ADRs involving the kidneys and liver, respectively. Patients with ADRs on the kidneys were older and comedication (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, metamizole and corticosteroids) was more common than in cases with ADRs on the liver. More patients with kidney- than liver-related ADRs had a fatal outcome (21.1% vs. 5.8%). In fatal cases with ADRs on the kidneys and with ADRs on the liver comedication was more common compared to non-fatal cases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Liver dysfunction was reported nearly three times more often than renal impairment. However, the kidneys need to be especially watched for, since a fatal outcome was considerably more common in renal failure. More precise and standardized recommendations on renal function tests might be necessary to support physicians in the complex treatment of RA.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13075-025-03551-6","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T11:29:33Z","timestamp":1743852573000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Methotrexate-related drug reactions on kidneys and liver in rheumatoid arthritis: an analysis of spontaneous reports in EudraVigilance"],"prefix":"10.1186","volume":"27","author":[{"given":"Kai","family":"Khoroshun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bantel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falk","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Jobski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"issue":"1","key":"3551_CR1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1136\/ard-2022-223356","volume":"82","author":"JS Smolen","year":"2023","unstructured":"Smolen JS, Landew\u00e9 RBM, Bergstra SA, Kerschbaumer A, Sepriano A, Aletaha D, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3\u201318.","journal-title":"Ann Rheum Dis"},{"issue":"4","key":"3551_CR2","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1093\/rheumatology\/keac520","volume":"62","author":"NK Bagri","year":"2023","unstructured":"Bagri NK, Ramanan A, Ramanan AV. Dr Yellapragada SubbaRow: the forgotten figure in the history of methotrexate. Rheumatology. 2023;62(4):1364\u20135.","journal-title":"Rheumatology"},{"key":"3551_CR3","unstructured":"European Medicines Agency (EMA). New measures to avoid potentially fatal dosing errors with methotrexate for inflammatory diseases. 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