Rheumatoid arthritis (RA) is a chronic inflammatory disease that can be managed with a range of therapeutic treatments. Methotrexate (MTX) is a first-line treatment for RA
however, its metabolism in RA patients can be complicated by multiple factors. Therefore, understanding these specific factors is crucial for optimizing the efficacy of MTX to provide improved therapeutic outcomes for patients. This article explores existing literature to examine how MTX metabolism in RA patients is impacted by other commonly used medications for RA. Additionally, the review explores the role of genetics by investigating the impact that single nucleotide polymorphisms (SNPs) have on MTX metabolism. Key findings from this review highlight how MTX metabolism can be enhanced or impaired based on specific combination therapies and how alternative treatments are considered with MTX treatment failure. MTX metabolism can also vary across different racial, ethnic, and population-based groups due to the presence of distinct SNPs in their genetic profiles. These results underscore the importance of personalized treatment approaches when treating RA patients with MTX, as its metabolism is influenced by factors such as drug interactions and SNPs. Future research is needed to expand our understanding of these factors to further improve therapeutic outcomes in RA patients.