{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:49:48Z","timestamp":1782125388942,"version":"3.54.5"},"reference-count":14,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the impact of overweight on methotrexate (MTX) efficacy and liver function in Japanese patients with rheumatoid arthritis (RA), and to explore whether liver dysfunction contributes to MTX dose limitation and treatment resistance in overweight individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cohort study included 71 RA patients who initiated MTX at a single center in Japan between April 2016 and December 2021. Patients were stratified by body mass index (BMI) into normal weight (&lt;\u200925.0\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) and overweight (\u2265\u200925.0\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) groups. Clinical data including DAS28\u2010CRP, liver enzyme levels, and MTX dosing were assessed at baseline and at 12, 24, and 48\u2009weeks. The primary outcome was the change in DAS28\u2010CRP (\u0394DAS28\u2010CRP) over time. Non\u2010parametric tests were used for comparisons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The overweight group showed significantly smaller \u0394DAS28\u2010CRP at 24 and 48\u2009weeks (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), suggesting a reduced clinical response to MTX, potentially related to lower MTX dose per body weight and elevated liver enzymes limiting dose escalation. While absolute MTX doses were similar, MTX dose per body weight was significantly lower in the overweight group throughout the study (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). MTX dose per body weight was negatively correlated with DAS28\u2010CRP at 48\u2009weeks (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.285,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.016). Overweight patients had higher AST, ALT, and \u03b3\u2010GTP levels, and a greater prevalence of fatty liver, suggesting liver dysfunction may have limited MTX escalation. Tender joint counts and CRP levels remained elevated in the overweight group, independent of osteoarthritic changes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overweight was associated with reduced MTX response in Japanese RA patients, potentially due to elevated liver enzymes limiting MTX dose escalation and leading to suboptimal dosing per body weight. Weight management and lifestyle interventions may improve treatment outcomes in overweight RA patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1756-185x.70487","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T01:06:48Z","timestamp":1763773608000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Overweight Impairs Escalating Optimal Methotrexate Dose and Effect via Liver Dysfunction in Japanese Patients With Rheumatoid Arthritis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-0563","authenticated-orcid":false,"given":"Soshi","family":"Takahashi","sequence":"first","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"},{"name":"The Center for Rheumatic Disease Shinko Hospital  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho","family":"Shibata","sequence":"additional","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8579-0109","authenticated-orcid":false,"given":"Miho","family":"Takahashi","sequence":"additional","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4924-1724","authenticated-orcid":false,"given":"Ayano","family":"Mori","sequence":"additional","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saori","family":"Hatachi","sequence":"additional","affiliation":[{"name":"The Center for Rheumatic Disease Shinko Hospital  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiharu","family":"Saito","sequence":"additional","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Kumagai","sequence":"additional","affiliation":[{"name":"The Shinko Institute for Medical Research Shinko Hospital  Kobe Japan"},{"name":"The Center for Rheumatic Disease Shinko Hospital  Kobe Hyogo 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