Low-Dose Methotrexate for the Treatment of Inflammatory Knee Osteoarthritis: A Randomized Clinical Trial.
OrthoEvidence Journal (OE Journal) - ACE Report
OE Journal. 2025;13(17):12 JAMA Intern Med . 2025 Jul 1;185(7):808-816.What this means for my practice?
In MRI-defined inflammatory knee OA, methotrexate 15 mg weekly did not reduce pain or effusion-synovitis versus placebo at 1 year; routine use for this indication is not supported. Clinically, prioritize non-DMARD strategies and phenotype-specific approaches; methotrexate may be reserved for research or carefully selected subgroups only. Limitations include predominance of female participants, dosing capped at 15 mg weekly (regional standard), COVID-era conduct, and small subgroup sizes, which may affect generalizability and power for modifiers of response
Study Summary
Two hundred fifteen patients with inflammatory knee osteoarthritis (OA) and MRI effusion-synovitis were randomized to methotrexate up to 15 mg weekly (n=108) or identical placebo (n=107). The primary outcome of interest was change in knee VAS pain and effusion-synovitis maximal area over 52 weeks. Secondary outcomes of interest included WOMAC (pain, stiffness, function, total), MRI effusion-synovitis volume, infrapatellar fat pad signal metrics, OMERACT-OARSI response, PHQ-9, SF-12, and structural MRI scores. Outcomes were assessed repeatedly to 52 weeks, with MRI at baseline and week 52. Overall, the results revealed no between-group differences for either primary endpoint and no significant differences across prespecified secondary outcomes.
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