{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T06:51:56Z","timestamp":1776840716095,"version":"3.51.2"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Methotrexate (MTX) is a cornerstone in treating juvenile idiopathic arthritis (JIA). The long\u2010term impact of MTX, particularly on pulmonary and liver function, remains a concern. We longitudinally examined the effects of MTX on pulmonary and hepatic function in the largest reported cohort to date.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this retrospective, single\u2010center study, patients with JIA receiving MTX (10\u201315\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) between 1993 and 2023 were analyzed. Pulmonary function tests (PFTs), including body plethysmography and diffusing capacity for carbon monoxide (DLCO), were performed annually (\u00b13 months) starting at age 5\u20136 years by professional lung function technicians according to international guidelines. Hepatic enzymes (glutamate pyruvate transaminase [GPT]\/alanine aminotransferase) were assessed quarterly with annual abdominal ultrasounds. Data points were compared using paired\n                      <jats:italic>t<\/jats:italic>\n                      \u2010tests against baseline and prior values.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 274 patients with JIA (189 female patients and 85 male patients) with a mean age at disease onset of 7.8 years were treated with MTX for a mean duration of 42.7 months (maximum 14.3 years), corresponding to 918 treatment\u2010years. No clinically relevant MTX\u2010associated lung disease occurred, and spirometric, lung volume, and diffusion parameters remained stable over time. One\u2010third of the 274 pt hat RANSIENT liver enzyme elevations in liver enzyme levels that resolved after dose adjustment or temporary interruption; only 17 of 63 affected patients required permanent discontinuation due to recurrent transaminase elevations. No structural hepatic pathology was detected. Overall, MTX was discontinued in 59% of patients, most commonly due to sustained remission (53%). Other reasons included GPT elevation, nausea, cytopenia, inefficacy, and noncompliance and accounted for only a small minority of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In children with JIA, long\u2010term treatment with MTX appears to be safe regarding the pulmonary outcome. Hepatic involvement was frequent but transient, occasionally requiring dose adjustment or discontinuation without long\u2010term complications.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/acr290000-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acr2.90000","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:19:45Z","timestamp":1774333185000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methotrexate Therapy in Juvenile Idiopathic Arthritis: No Clinically Relevant Pulmonary Impairment but Frequent Transient Liver Enzyme Elevations in a Longitudinal Single\u2010Center Pediatric Cohort of 274 Children Over 30 Years"],"prefix":"10.1002","volume":"8","author":[{"given":"Janosch","family":"We\u00dfling","sequence":"first","affiliation":[{"name":"Division of Paediatric Pneumology, Allergology and Neonatology, Department of Paediatrics Hannover Medical School  Hannover Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Leiskau","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center G\u00f6ttingen Georg August University  G\u00f6ttingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Dressler","sequence":"additional","affiliation":[{"name":"Division of Paediatric Pneumology, Allergology and Neonatology, Department of Paediatrics Hannover Medical 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