Methotrexate Shows Promise in Treating OA
Recent research findings support the potential role of methotrexate (MTX) in management of osteoarthritis (OA) symptoms, but the overall power of the existing literature remains limited, according to investigators reporting in Inflammapharmacology.
OA lacks consistently effective pharmacologic treatments. Due to its established anti-inflammatory efficacy in rheumatoid arthritis, the researchers aimed to investigate whether it could be efficacious in relieving inflammation and pain in OA, especially joint stiffness and pain in the knee and hand.
They conducted a comprehensive literature search across PubMed, Google Scholar, Embase, Web of Science, and Cochrane databases to identify randomized controlled trials (RCTs) evaluating MTX in OA. Risk ratios (RR) were synthesized for binary outcomes, while standard mean differences (SMD) and mean differences (MD) with 95% confidence intervals (CI) were pooled for continuous outcomes. The GRADE framework was employed to assess the quality of evidence.
The meta-analysis included 5 RCTs that included 465 participants, with 229 assigned to MTX treatment. The mean participant age across studies ranged from 52.4 to 67.5 years. MTX demonstrated a statistically significant effect in reducing stiffness in both knee and hand OA at the end of follow-up (SMD −0.36; 95% CI −0.57 to −0.15; *P* < .01), as well as at the 6-month follow-up (SMD −0.48; 95% CI −0.70 to −0.27; *P* < .01).
The authors conclude, “Methotrexate significantly reduced knee and hand stiffness at the end of follow-up,” suggesting a measurable clinical benefit. However, they also cautioned that “current literature might be underpowered,” underscoring the need for larger, well-designed RCTs to confirm these preliminary results and further evaluate the therapeutic role of MTX in OA.
Reference: Queiroz I, Pimentel T, Ruelas MG, et al. Methotrexate for osteoarthritis: a systematic review meta-analysis of randomized controlled trials. Inflammopharmacology. 2025;33(1):135–144.
