Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Jan;33(1):135-144.
doi: 10.1007/s10787-024-01604-x. Epub 2024 Nov 30.

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

Ivo Queiroz  1 , Túlio Pimentel  2 , Mariano Gallo Ruelas  3 , Arthur Henrique Tavares  4 , Lucas M Barbosa  5 , Maria L R Defante  6 , Giovanna N Leandro  2 , Arthur Ribeiro Monteiro  2 , Fernando Nunes Pimentel  7
Affiliations
Meta-Analysis

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

Ivo Queiroz et al. Inflammopharmacology. 2025 Jan.

Abstract

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.

Keywords: Arthritis treatment; Knee pain; Methotrexate; Osteoarthritis; Pain reduction.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflict of interest: All authors report no relationships that could be construed as a conflict of interest. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

References

    1. Balduzzi S, Rücker G, Schwarzer G (2019) How to perform a meta-analysis with R: a practical tutorial. Evid Based Mental Health 22:153–160. https://doi.org/10.1136/ebmental-2019-300117 - DOI
    1. Bellamy N, Campbell J, Haraoui B et al (2002) Clinimetric properties of the AUSCAN Osteoarthritis Hand Index: an evaluation of reliability, validity and responsiveness. Osteoarthr Cartil 10:863–869. https://doi.org/10.1053/joca.2002.0838 - DOI
    1. Centre Hospitalier Universitaire de Nice (Responsible Party) Erosive Osteoarthritis of the Hands: Treatment by Methotrexate Versus Placebo (ADEM)
    1. Da Costa BR, Saadat P, Basciani RM et al (2021) Visual Analogue Scale has higher assay sensitivity than WOMAC pain in detecting between-group differences in treatment effects: a meta-epidemiological study. Osteoarthr Cartil 29:304–312. https://doi.org/10.1016/j.joca.2020.10.004 - DOI
    1. Diakonhjemmet Hospital A Post-trial Follow-up of MERINO Participants to Evaluate Long-term Effects of Methotrexate Treatment in Adults With Erosive Hand OA. (MERINO:2)

MeSH terms

LinkOut - more resources