{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T16:06:59Z","timestamp":1793203619851,"version":"4.5.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Intern Med"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"Importance<\/jats:title>A recent study reported that methotrexate may reduce joint pain in patients with inflammatory hand osteoarthritis (OA). However, it remains unknown whether methotrexate has similar effects on inflammatory knee OA.<\/jats:p><\/jats:sec>Objective<\/jats:title>To examine whether methotrexate has symptom-relieving and disease-modifying effects for participants with knee OA and effusion-synovitis.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This multicenter, placebo-controlled randomized clinical trial was conducted at 11 sites in China between July 18, 2019, and January 15, 2023. Community-dwelling patients with inflammatory knee OA with effusion-synovitis on magnetic resonance imaging were included.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Participants were randomly assigned (1:1) to receive methotrexate, up to 15 mg weekly, or placebo using block randomization, stratified by study site.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary outcomes were knee visual analog scale (VAS) pain change and effusion-synovitis maximal area change, over 52 weeks in the intention-to-treat population.<\/jats:p><\/jats:sec>Results<\/jats:title>Of 278 participants screened, 215 participants (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomized (108 to the methotrexate group; 107 to the placebo group), and 175 (81%) completed the trial. Changes in VAS pain and effusion-synovitis maximal area were not significantly different between the methotrexate and placebo group over 52 weeks (between-group difference, 0.3 mm [95% CI, \u22126.7 to 7.3 mm] for VAS pain; 0.1 cm2<\/jats:sup> [95% CI, \u22120.8 to 1.0 cm2<\/jats:sup>] for effusion-synovitis maximal area). No significant between-group differences were found for any of the prespecified secondary outcomes. At least 1 adverse event occurred in approximately 32 participants (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The results of this randomized clinical trial show that, compared to placebo, low-dose methotrexate did not reduce pain or effusion-synovitis over 52 weeks in patients with knee OA and effusion-synovitis.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03815448<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamainternmed.2025.1359","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T15:00:57Z","timestamp":1748876457000},"page":"808","source":"Crossref","is-referenced-by-count":24,"title":["Low-Dose Methotrexate for the Treatment of Inflammatory Knee Osteoarthritis"],"prefix":"10.1001","volume":"185","author":[{"given":"Zhaohua","family":"Zhu","sequence":"first","affiliation":[{"name":"Clinical 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