Efficacy and safety of methotrexate in osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

Abstract

OBJECTIVE To evaluate the efficacy and safety of methotrexate (MTX) for osteoarthritis (OA). DESIGN A systematic search of databases and clinical trial registers was conducted in September 2024 to identify randomized controlled trials (RCTs) comparing MTX with placebo. The evaluation focused on OA symptoms, including pain and function; quality of life; safety and OA-related biomarkers (biochemical and imaging markers). Meta-analysis and the minimum clinically important difference (MCID) were utilized to determine statistical and clinical significance. The risk of bias and certainty assessment were evaluated using the RoB 1 tool, the RoB-ME tool, and the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) framework. RESULTS Six RCTs involving 602 participants were included, all with a low risk of bias. Compared to the placebo, MTX significantly relieved pain (SMD, -0.44; 95% CI, -0.67 to -0.20, P = 0.0003) in patients with OA (knee and hand). Functional improvement with MTX was observed only in patients with knee OA (WMD, -7.36; 95% CI, -14.34 to -0.38, P = 0.045), while not observed in those with hand OA (WMD, -0.70; 95% CI, -2.52 to 1.12, P = 0.45). The point estimates did not exceed the MCID of each scale, suggesting the possible clinical significance of the findings. No differences were observed for quality-of-life outcome (SMD, -0.74; 95% CI, -153 to 0.05, P = 0.07). Besides, MTX did not significantly increase the incidence of adverse events (AEs) compared to placebo (RR, 0.88; 95% CI, 0.75 to 1.02, P = 0.09). CONCLUSIONS Methotrexate can alleviate pain in patients with osteoarthritis and improve functional recovery in knee OA without raising safety concerns.