Table 1.
Therapies Effective Against RA and ASCVD.
| DMARDs | ||
|---|---|---|
| Name of Drug | Mechanism of Action | |
| Anti-rheumatic Properties | Atheroprotective Properties | |
| Methotrexate | Inhibits dihydrofolate reductase and several immune pathways involved in purine and pyrimidine synthesis. |
Enhances macrophage cholesterol efflux and prevents foams cell differentiation and activation. Upregulates free radical scavenging; improves endothelial function. |
| Sulfasalazine | Reduces production of inflammatory cytokines, likely through inhibition of NF-κB activation. |
Prevents arachidonic acid-mediated platelet aggregation, decreases adhesion of monocytes and leukocytes, and increases HDL-C. |
| Hydroxychloroquine | Interferes with toll-like receptor signaling, reduces calcium signaling in B and T cells and matrix metalloprotease activity | Positively impacts insulin sensitization, promotes anti-atherogenic lipid profile. Anti-thrombotic and anticoagulant properties. |
| Tumor Necrosis Factor (TNF)-α Inhibitors | ||
| Etanercept Infliximab Adalimumab |
Biologics that inactivate TNF-α. Etanercept is a fusion protein of human immunoglobulin 1 Fc domain and TNF-α receptor. Infliximab is a mouse-human chimeric anti-human TNF-α antibody Adalimumab is a human anti-human TNF-α antibody |
TNF-α promotes numerous inflammatory responses associated with atherosclerosis, including induction of vascular adhesion and monocyte/macrophage proliferation. TNF-α impacts lipid metabolism by stimulating liver triglyceride production. |
| IL-6 Inhibitors | ||
| Tocilizumab | Inhibits IL-6 which contributes to inflammation and antibody production through its action on T cells, B cells, monocytes and neutrophils |
Decreases inflammatory proteins such as serum amyloid A, and restores the anti-atherogenic function of HDL by increasing HDL cholesterol efflux capacity. |
| JAK Kinase Inhibitors | ||
| Tofacitinib | Small molecules that target the JAK-STAT signaling pathway. Reduce expression of cytokine related genes. | Risk of adverse cardiovascular events still being evaluated. Many studies show no difference compared to placebo or biologic |
| Upadacitinib | More JAK1 selective | |