The safety and efficacy in reducing serum cytokines led to a preliminary study of 18 patients with rheumatoid arthritis (RA) in which VNS resulted in a significant drop in IL-6 levels and clinical improvement in both study groups: i) a treatment-naïve group with newly diagnosed RA; ii) a treatment-refractory group that failed standard treatments for RA, including methotrexate and two or more biological agents with distinct mechanisms of action, e.g., anti-TNF, anti-IL6R, or anti-CD20. Here, IL6R is linked to rheumatoid arthritis.