Methotrexate treatment for pain due to osteoarthritis of the hand and knee: A systematic review and meta analysis

Osteoarthritis is a chronic health condition that causes substantial morbidity globally. Methotrexate has been explored as a therapeutic given its use in inflammatory arthritis. This paper aims to summarize and evaluate the current literature regarding methotrexate as treatment for osteoarthritis. We identified two randomized controlled trials testing methotrexate for hand pain (161 total subjects; 79 control, 82 experimental group) and three randomized controlled trials testing methotrexate for knee pain (313 total subjects; 157 control, 156 experimental). We performed a risk of bias assessment on all included studies. Our meta-analysis revealed significant reduction in hand pain with methotrexate use at 3-4 months (95% CI: -0.66, -0.06), as well as for knee pain at 6 months (95% CI: -1.26, -0.07), but not at 3-4 months (95% CI: -0.69, +0.09). Finally, we performed sensitivity analysis excluding high risk of bias studies, but when looking at all outcomes, this did not change significance for any of the groups.