Methotrexate

Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers.

Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis.

Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.

Author/s:

Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher

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

Megan George — Tue, 14 Oct 2025 13:08:01 +0000

Date Added:

October 14, 2025

Journal/Publication:

Medicine

Publication Date:

October 10, 2025

URL:

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

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1097/MD.0000000000044994

Keywords

MeSH

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

Free full text

View

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

Treatment of Atopic Dermatitis

Megan George — Thu, 21 Aug 2025 15:59:01 +0000

Date Added:

August 21, 2025

Journal/Publication:

JAMA

Publication Date:

August 20, 2025

URL:

Treatment of Atopic Dermatitis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.11589

Keywords

dermatology

atopic dermaitis

A review of currently available treatment methods for patients with atopic dermatitis. James W. Mold, MD, MPH

Free full text

View

Not Available

Author/s:

Aaron M. Drucker

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

View

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

Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People

Brian Desmarais — Wed, 26 Jun 2019 21:56:55 +0000

Date Added:

June 26, 2019

Publisher:

UCSF Center of Excellence for Transgender Health

Publication Date:

June 17, 2019

URL:

Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

Keywords

MeSH

Antineoplastic Combined Chemotherapy Protocols

Cytarabine

Etoposide

Methotrexate

referral and consultation

Standard of Care

Guidelines for providing gender-affirming care for LGBTQ patients. I recommend pages 15-18 even if you have no interest in the rest of the material in the guideline. James W. Mold, MD, MPH

Free full text

View

Introduction to the guidelines The Center of Excellence for Transgender Health (CoE) at the University of California – San Francisco is proud to present these Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People. Transgender people have a gender identity that differs from the sex which they were assigned at birth, and are estimated to represent 0.5% of the U.S. population.[1] Numerous needs assessments have demonstrated that transgender people encounter a range of barriers to accessing primary health care. A 2006 survey of more than 600 transgender people in California found that 30% postponed seeking medical care due to prior disrespect or discrimination, and that 10% were primary care outright.[2] The 2011 National Transgender Discrimination Survey of more than 6000 transgender people in all 50 U.S. states found several noteworthy disparities, including 28% who delayed care due to past discrimination and 19% who were denied care outright. Most alarmingly, 50% of respondents reported having to teach their providers about their own healthcare.[3] These guidelines aim to address these disparities by equipping primary care providers and health systems with the tools and knowledge to meet the health care needs of their transgender and gender nonconforming patients. These guidelines expand on the original UCSF Primary Care Protocol for Transgender Care, which since its launch in 2011 has served thousands of providers and policymakers across the U.S. and around the world; the page on hormone administration alone received more than 5000 visitors in the month of November, 2015. These Guidelines complement the existing World Professional Association for Transgender Health Standards of Care and the Endocrine Society Guidelines in that they are specifically designed for implementation in every day evidence-based primary care, including settings with limited resources.[4,5] The overall structure and list of topics for inclusion were developed in consultation with the CoE’s Medical Advisory Board (MAB), a diverse group of expert clinicians from a variety of academic and community based settings. Also contributing to the overall design and structure was a review of the range of consultation requests received by the CoE since the 2011 launch of the original Protocol. The guidelines were then written using an authorship – peer review approach. Primary authors from both within and outside the MAB were invited for individual topics, after which a peer review and modified consensus process was used to arrive at the final guidelines presented here. The diverse authorship allows the development of a broadly applicable document, rather than one that solely reflects the practice at a single academic medical center, such as UCSF. These guidelines would not be possible without the contributions of our Medical Advisory Board and other authors and reviewers, as well as the support of my CoE colleagues JoAnne Keatley, MSW and E. Michael Reyes, MD, MPH, as well as Lissa Moran who assisted immensely with literature reviews, bibliography management, version control, copy editing, formatting, and compiling peer reviewer comments. Ben Zovod also assisted with literature reviews, bibliography management, and compiling peer reviewer comments. Their dedication and hours of hard work has resulted in a final product that is relevant, broadly applicable, evidence based, and scientifically sound. I hope you find these guidelines useful and welcome any feedback or questions, which are June 17, 2016 2 Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People helpful in framing future revisions. Thank you for caring about the health of transgender and gender nonconforming people. Madeline B. Deutsch, MD, MPH Editor Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People Director of Clinical Services Center of Excellence for Transgender Health Associate Professor of Clinical Family and Community Medicine Department of Family and Community Medicine University of California, San Francisco Madeline.Deutsch@ucsf.edu