Effectiveness of methotrexate in the treatment of osteoarthritis: modern views

Abstract

Background. Methotrexate (Mtx) is known for its disease-modifying potential in the treatment of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, systemic vasculitis. There are attempts to use Mtx also in other rheumatic diseases, particularly in non-immune diseases such as osteoarthritis. Objective(s). To determine the efficacy of methotrexate indication in the complex treatment of osteoarthritis of the hand and knee joints according to recent studies (within the last 5 years). Materials and methods. The medical search engine of reputable databases PubMed, SciensDirect, Lancet, Google Shcolar were searched and 265 publications were found, of which 6 were classified as randomized controlled trials evaluating the efficacy of methotrexate in the treatment of osteoarthritis of the hands and knees compared with placebo. Results. In a double-blind, randomized, placebo-controlled study conducted in 2023, of the 202 participants assessed for eligibility, 97 (48%) were randomized to receive methotrexate (n=50) or placebo (n=47). The results of the study demonstrated that treatment of osteoarthritis of the hand with synovitis with 20 mg of methotrexate for 6 months had a moderate, but potentially clinically significant, effect in reducing pain. A meta-analysis conducted in 2025 with 465 patients from 5 randomized clinical trials concluded that this drug demonstrates efficacy at the end of the follow-up period regarding pain and stiffness in osteoarthritis of the knee. Conclusion(s). Methotrexate has demonstrated some favorable clinical results in diminishing the intensity of pain syndrome and stiffness in the joints of the hands and knees, especially in clinical variants with inflammatory phenotype (reactive synovitis) of the primary osteoarthritis.