Ion Channel Modulators for Treatment-Resistant Rheumatoid Arthritis: Focus on Inflammation

Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease that, in most cases, mainly attacks synovial tissues within the joints. The pathogenesis of RA is not fully understood, but the main features are generation of autoantibodies, induced joint inflammation, and erosion of cartilage. Treatment of RA includes anti-inflammatory, chemotherapeutic drugs such as methotrexate, sulfasalazine, and biological therapy, linked against tumor necrosis factor α. However, a significant group of RA patients do not respond to or tolerate the treatments, so new drugs are needed. One possibility is to use (“reposition”) existing drugs from other therapeutic classes and disease areas to address the problem of treatment-resistant RA. In this regard, various ion channel modulators, including cardiovascular drugs and antiepileptics, have shown promising results in animal models of RA and joint inflammation. This perspective article focuses on ion channel modulators that target the process of inflammation, including those that alter the level of cytokines, induce alterations in joint structures, and impact on clinical signs in RA models.