Overweight Impairs Escalating Optimal Methotrexate Dose and Effect via Liver Dysfunction in Japanese Patients With...

Area of Science:

• Rheumatology
• Pharmacology
• Hepatology

Background:

• Rheumatoid arthritis (RA) management often involves methotrexate (MTX).
• Overweight status can influence drug efficacy and safety.
• The impact of overweight on MTX in Japanese RA patients requires further investigation.

Purpose of the Study:

• To assess how overweight affects MTX efficacy and liver function in Japanese RA patients.
• To determine if liver dysfunction contributes to MTX dose limitation and treatment resistance in overweight RA patients.

Main Methods:

• Retrospective cohort study of 71 Japanese RA patients initiating MTX.
• Patients stratified into normal weight (<25.0 kg/m²) and overweight (≥25.0 kg/m²) groups.
• Assessed DAS28-CRP, liver enzymes, and MTX dosing over 48 weeks.

Main Results:

• Overweight RA patients exhibited significantly reduced MTX efficacy (smaller ΔDAS28-CRP at 24 and 48 weeks).
• Overweight individuals had lower MTX dose per body weight and elevated liver enzymes (AST, ALT, γ-GTP), suggesting dose-limiting liver dysfunction.
• Higher prevalence of fatty liver in overweight patients correlated with poorer MTX response.

Conclusions:

• Overweight is linked to diminished MTX response in Japanese RA patients.
• Elevated liver enzymes and subsequent MTX dose limitation may explain reduced efficacy in overweight RA patients.
• Weight management and lifestyle interventions are recommended for overweight RA patients to improve treatment outcomes.