<![CDATA[Rheumatoid arthritis is a chronic autoimmune disease characterised by persistent inflammation and functional impairment. Methotrexate remains the cornerstone therapy; however, its effects on physical function have not been consistently evaluated. To evaluate the effectiveness of methotrexate-based therapy on inflammatory control and physical function in patients with rheumatoid arthritis. This systematic review followed PRISMA guidelines. Literature searches were conducted in PubMed, Scopus, the Cochrane Library, SpringerLink, and ScienceDirect for studies published between 2016 and 2025. Eligible studies were randomised controlled trials involving adult patients with rheumatoid arthritis receiving methotrexate as monotherapy or combination therapy. The primary outcome was physical function assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI), while secondary outcomes included disease activity measures. Eight randomised controlled trials were included. Methotrexate-based therapy consistently reduced disease activity across studies, with combination regimens generally demonstrating greater inflammatory suppression than monotherapy. Improvements in physical function were observed in several studies, particularly in combination therapy groups; however, these improvements were not consistently proportional to reductions in inflammatory activity. Functional outcomes were also reported heterogeneously across studies. Methotrexate-based therapy is effective in controlling inflammatory activity in rheumatoid arthritis but does not consistently translate into proportional improvements in physical function. Persistent impairment may also be influenced by structural joint damage, chronic pain, fatigue, and psychosocial factors. ]]>
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