The effectiveness and safety of methotrexate in the intervention of osteoarthritis: A systematic review and meta-analysis of randomized controlled trials

The findings of this meta-analysis suggest that methotrexate is both safe and effective for treatment of pain and joint stiffness in patients with osteoarthritis. James W. Mold, MD, MPH

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Background:
Osteoarthritis (OA) is a prevalent chronic joint disorder among middle-aged and older adults, characterized by progressive cartilage degeneration, subchondral bone remodeling, and osteophyte formation, leading to joint pain, stiffness, dysfunction, and reduced quality of life. With the global aging population, OA imposes a growing socioeconomic burden, yet no disease-modifying therapy is currently available—particularly for moderate-to-severe stages. Emerging evidence implicates synovial inflammation as a central contributor to OA symptoms and progression, raising interest in methotrexate (MTX), a well-established, low-dose anti-inflammatory agent used safely in rheumatoid arthritis. Preliminary studies suggest MTX may alleviate OA-related pain, but findings from randomized controlled trials (RCTs) have been inconsistent and limited in number. Given recent new RCTs and the heterogeneity of existing outcomes, an updated systematic review and meta-analysis is urgently needed to clarify the efficacy and safety of MTX in OA and inform future clinical trial design.

Methods:
PubMed, ClinicalTrials, Web of Science, Cochrane Library and other databases were searched to find randomized controlled trials (RCT) of MTX treatment of OA. Methodological quality was assessed using the Cochrane "risk of bias" assessment tool, and the meta-analysis was conducted using Review Manager (RevMan) version 5.3 (The Cochrane Collaboration, London, UK).

Results:
Fifteen RCTs involving 1591 participants were included in this review. The meta-analysis results showed that the ineffective rate in the experimental group was lower [RR: 0.40 (0.24, 0.67), P = .004]; the VAS in the experimental group was lower [WMD: −0.66 (−1.08, −0.24), P = .002]; the WOMAC score-stiffness in the experimental group was lower [WMD: −0.72 (−1.04, −0.41), P < .00001]; the WOMAC score-function in the experimental group was lower [WMD: −7.72 (−13.56, −1.87), P = .01]. The adverse events in the experimental group were not statistically significant compared with the control group [RR: 1.04 (0.77, 1.42), P = .78].

Conclusion:
MTX demonstrates potential in effectively alleviating pain, improving joint function, and slowing disease progression in patients with OA. Its safety profile is comparable to that of control treatments, making it a viable and reliable therapeutic option worthy of broader clinical application.

Author/s:

Wan, Lifei, Yang, Qianyue, Yang, Kailin, Zeng, Liuting, Sun, Lingyun

Uveitis in Adults

Hope Smashey — Tue, 01 Jul 2025 17:07:23 +0000

Date Added:

July 1, 2025

Journal/Publication:

JAMA

Publication Date:

May 28, 2025

URL:

Uveitis in Adults

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.4358

Keywords

human leukocyte antigen

PMID (1):

40434762

MeSH

human leukocyte antigen

corticosteroid

antimicrobial

Inflammation

An evidence-based review of the diagnosis, causes, and treatment of uveitis in adults. James W. Mold, MD, MPH

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Importance: Uveitis is characterized by inflammation of the uvea—the middle portion of the eye composed of the iris, ciliary body, and choroid—causing eye redness, pain, photophobia, floaters, and blurred vision. Untreated uveitis may cause cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss.

Observations: Uveitis predominantly affects individuals aged 20 to 50 years. Anterior uveitis affects the iris and ciliary body (41%-60% of cases); intermediate uveitis affects the pars plana (attachment point of vitreous humor) and peripheral retina (9%-15%); posterior uveitis involves the choroid and/or retina (17%-23%); and panuveitis involves all uveal layers (7%-32%). Uveitis is classified as noninfectious or infectious, with toxoplasmosis, herpes, tuberculosis, and HIV comprising 11% to 21% of infectious cases in high-income countries and 50% in low- and middle-income countries. Incidence and prevalence of uveitis are influenced by genetic factors (eg, human leukocyte antigen–B27), environmental factors (eg, air pollution), and infection rates. In the US and Europe, 27% to 51% of uveitis cases are idiopathic, and 37% to 49% are associated with systemic disease, such as axial spondyloarthritis. Treatment goals are to induce and maintain remission while minimizing corticosteroid use to reduce corticosteroid-related adverse effects. Infectious uveitis requires systemic antimicrobial treatment. Active inflammatory disorders associated with uveitis should be treated by the appropriate specialist (eg, rheumatologist). Treatment for uveitis depends on subtype; anterior uveitis is treated with topical corticosteroids, and mild intermediate uveitis may be monitored without initial treatment. Patients with moderate to severe intermediate uveitis, posterior uveitis, and panuveitis are at high risk of sight-threatening complications and require systemic and/or intravitreal corticosteroids and immunosuppressive agents. For posterior uveitis, first-line therapy with disease-modifying antirheumatic drugs such as methotrexate achieved remission of inflammation in 52.1% (95% CI, 38.6%-67.1%) of patients, and mycophenolate mofetil controlled inflammation in 70.9% (95% CI, 57.1%-83.5%). In patients who do not improve or worsen with first-line therapy, adalimumab extended time to treatment failure to 24 weeks vs 13 weeks with placebo and reduced frequency of treatment failure from 78.5% to 54.5% (P < .001).

Conclusions and Relevance: Uveitis is characterized by inflammation of the uvea and primarily affects adults aged 20 to 50 years. For noninfectious anterior uveitis, corticosteroid eyedrops are first-line treatment. For posterior noninfectious uveitis, disease-modifying antirheumatic drugs are first-line therapy; biologics such as adalimumab are second-line treatment for patients with inflammation refractory to treatment. Uveitis caused by systemic infection should be treated with antimicrobials, and local or systemic steroids may be used depending on the severity of uveitis and the specific microorganism.

Author/s:

Panayiotis Maghsoudlou, Simon J. Epps, Catherine M. Guly