JAMA Intern Med

Low-dose methotrexate misses mark in knee OA trial

June 5, 2025

Findings from this randomized placebo-controlled trial don’t support the use of methotrexate for symptom relief or disease modification in people with inflammatory knee osteoarthritis (OA).

Study details: This multicenter, double-blind, randomized trial enrolled 215 adults (mean age 60 years; 89% female) with MRI-confirmed inflammatory knee OA and effusion-synovitis at 11 sites in China. Participants were randomized to receive methotrexate (up to 15 mg weekly) or placebo for 52 weeks. Primary outcomes were change in knee pain (visual analog scale; VAS) and effusion-synovitis maximal area on MRI.

Results: At 52 weeks, there wasn’t a significant between-group difference in change in VAS pain (0.3 mm; 95% confidence interval [CI], -6.7 to 7.3 mm) or effusion-synovitis area (0.1 cm²; 95% CI, -0.8 to 1.0 cm²). Secondary outcomes, including function and quality of life, were similar between groups. Adverse event rates were also similar: 29.6% with methotrexate vs. 24.3% with placebo.

Source:

Zhu Z, et al. (2025, June 2). JAMA Intern Med. Low-Dose Methotrexate for the Treatment of Inflammatory Knee Osteoarthritis: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40455462/