Methotrexate for osteoarthritis: a systematic review meta-analysis of randomized controlled trials.

Background: Osteoarthritis (OA) is a common joint disorder causing pain and stiffness, with limited effective treatment options. Methotrexate, known for its anti-inflammatory properties in rheumatoid arthritis, is being explored as a treatment for OA. This study evaluates Methotrexate's efficacy compared to placebo in reducing OA symptoms, such as stiffness in the knee and hand, and its impact on pain, physical function.

Methods: We systematically searched PubMed, Google Scholar, Embase, Web of Science, and Cochrane databases for randomized controlled trials (RCTs), analyzing the efficacy of Methotrexate compared to placebo in patients with OA. We pooled risk ratios (RR) for binary outcomes. For continuous outcomes, we used standard mean difference (SMD) and mean difference (MD) with 95% confidence intervals (CI). Outcomes included were related to knee and hand pain, knee stiffness, and similar outcomes. We used R version 4.4.1 for statistical analyses. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach evaluated the quality of evidence.

Results: This analysis included 5 RCTs comprising 465 patients, of whom 229 were randomized to Methotrexate. The age ranged from 52.4 to 67.5 years among studies. Compared with placebo, Methotrexate significantly reduced knee and hand stiffness at the end of follow-up (SMD - 0.36; 95% CI - 0.57 to - 0.15; p< 0.01), knee and hand stiffness at 6 months of follow-up (SMD - 0.48; 95% CI - 0.70 to - 0.27; p< 0.01).

Conclusion: Methotrexate significantly reduced knee stiffness in both knee and hand OA. However, current literature might be underpowered, more robust RCTs are necessary to validate these findings.