Vagus nerve stimulation in patients with rheumatoid arthritis: 24 month safety an efficacy

Background/Purpose: RA is a debilitating chronic disease with an unmet need for additional therapeutic approaches. Modulating innate neuro-immune re ex pathways by stimulation of the vagus nerve (VNS) could represent a novel means of treating RA (van Maanen MA et al. Nat Rev Rheumatol. 2009 ; 5:229-32). We recently reported a 12-week proof of concept study using a VNS device, approved for drugresistant epilepsy, showing reductions in the DAS28-CRP and in TNF-α and IL-6 levels (Koopman FA et al. PNAS 2016 ; 113:8284). To understand the long term safety and e cacy of this novel treatment approach, we followed the patients in a 24 months long-term extension study and report on the safety and clinical e cacy data. Methods: In the primary study, VNS devices were implanted into 17 RA patients, mostly with insu cient response to multiple conventional and biologic DMARDs, on stable background of methotrexate (≤25 mg weekly) therapy. The devices electrically stimulated the vagus nerve, 1-4 min/day, over a 12 week open label period. On completion, subjects were o ered to enroll into a follow-up study, where the study physicians were given exibility to alter VNS dosing parameters and/or to add a biologic DMARD to the treatment regimen. DAS28-CRP and Health Assessment Questionnaire-Disability Index (HAQ-DI) were collected over 2 years. Results: All subjects electively continued on VNS treatment through 24 months of the long term follow-up study. Biologic DMARDs were started in 1 and restarted in 8 of 17 subjects ; of these, 4 were nonresponders to VNS in the primary study, and 5 had stable improvement but had not yet achieved disease remission on VNS alone (Table 1). At the start of the follow-up study, the mean DAS28-28 and HAQ-DI were signi cantly reduced compared to the pre-implant baseline (mean di erence± SE in DAS28-CRP = -1.60± 0.37, p