The Effects of Disease-Modifying Antirheumatic Drugs on Cardiovascular Risk in Inflammatory Joint Diseases: Current Evidence and Uncertainties

Abstract

Patients with inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, have an elevated risk of cardiovascular complications due to systemic inflammation, immune-mediated endothelial dysfunction, and associated metabolic changes. Disease-modifying antirheumatic drugs (DMARDs) influence cardiovascular risk through their effects on inflammation, lipid metabolism, and endothelial function. Methotrexate has demonstrated cardioprotective properties, likely mediated through anti-inflammatory mechanisms rather than direct metabolic effects. However, other conventional DMARDs, such as sulfasalazine and hydroxychloroquine, also continue to play a role in routine practice; their cardiovascular effects appear more heterogeneous and less well established. Biologic DMARDs, particularly tumor necrosis factor (TNF) inhibitors, are associated with a reduction in major cardiovascular events despite inducing lipid profile alterations. However, data on newer biologic agents, such as interleukin (IL)-17 and IL-23 inhibitors, remain limited. Janus kinase (JAK) inhibitors present concerns regarding dyslipidemia and thrombotic risk, necessitating individualized cardiovascular risk assessment. Nonsteroidal anti-inflammatory drugs (NSAIDs) remain controversial due to their potential to exacerbate cardiovascular risk, particularly with long-term use. Given the variability in drug effects, treatment strategies must balance effective disease control with cardiovascular safety. This narrative review summarizes current evidence on the impact of both conventional and biologic DMARDs on cardiovascular risk, drawing from randomized clinical trials and real-world observational data. The review also compares available data across different inflammatory joint diseases and highlights areas of uncertainty that remain in clinical decision-making. A multidisciplinary and individualized approach remains essential for optimizing long-term cardiovascular outcomes in these patients.

Keywords: autoimmune; axial spondyloarthritis; cardiovascular risk; disease-modifying antirheumatic drugs; immune-mediated diseases; psoriatic arthritis; rheumatoid arthritis.