Use of leflunomide plus TNF-α inhibitors in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory immune-mediated systemic disease which primarily affects the joints. Leflunomide (LFN) is a disease modifying anti-rheumatic drugs (DMARDs) which acts by inhibiting the synthesis of pyrimidines. Several trials have demonstrated the efficacy and safety of LFN alone or in combination with biological agents such as tumor necrosis factor-α (TNF-α) inhibitors in the treatment of RA patients. TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenesis of RA. TNF-α inhibitors have demonstrated efficacy as monotherapy or in combination with other anti-inflammatory or DMARDs in the treatment of RA. Five TNF-α inhibitors are available for clinical use and include infliximab, adalimumab, golimumab, certolizumab pegol and etanercept. In this editorial, we briefly discuss the efficacy and safety of LFN and TNF-α inhibitors in the treatment of RA, and the potential beneficial effect of both LFN and TNF-α inhibitors in improving the endothelial dysfunction and in reducing the risk of acute cardiovascular and/or cerebrovascular events.