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Methotrexate for Osteoarthritis: What Does the Evidence Say?
Marina De Castro Fidalgo E Costa1,2, Frederique Ponchel1,2, Kierran Flack1,2
1Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, 2nd Floor Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK.
Drugs & Aging
|January 22, 2026
Summary
Methotrexate (MTX) shows potential for treating osteoarthritis (OA) pain, particularly in knee and hand OA, when used at higher doses. Further research is needed to optimize its use and cost-effectiveness.
Area of Science:
- Rheumatology
- Pharmacology
- Immunology
Background:
- Osteoarthritis (OA) is a major cause of disability with limited treatment options.
- Inflammation is a key factor in OA, making anti-inflammatory agents a potential therapeutic target.
- Methotrexate (MTX) is effective in rheumatoid arthritis (RA) due to its immunomodulatory effects.
Purpose of the Study:
- To review the evidence for methotrexate (MTX) efficacy and safety in treating knee and hand osteoarthritis (OA).
- To explore the potential of MTX as a pharmacotherapy for OA symptoms.
Main Methods:
- Systematic review of seven randomized controlled trials and two observational studies.
- Analysis of studies investigating MTX in patients with knee and hand OA.
- Evaluation of varying sample sizes, populations, MTX dosages, and follow-up durations.
Main Results:
- Conflicting outcomes regarding MTX's effect on OA symptoms across studies.
- Larger trials using higher MTX doses (> 15 mg/week) showed consistent benefits for knee and hand OA pain.
- MTX demonstrated a favorable safety profile in the reviewed studies.
Conclusions:
- Methotrexate (MTX) shows promise as a treatment for osteoarthritis (OA) pain, especially with higher doses.
- Further research is required to refine MTX dosing, assess long-term effects, and evaluate cost-effectiveness.
- Stratifying OA patients by phenotype, considering inflammation, may improve MTX treatment selection.
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