Effects of Chronic Non-Invasive Vagus Nerve Stimulation in an Asplenic Individual with Rheumatoid Arthritis: A Single Subject Trial

Abstract

Background: Rheumatoid arthritis (RA) is an autoimmune disease for which the goal is disease remission or near-remission on a treat-to-target basis. Noninvasive vagus nerve stimulation (nVNS) represents a new era as an alternative to drug-resistant therapy, providing evidence of the anti inflammatory neuroimmunological (NIM) effect of vagal stimulation along with the restoration of autonomic nervous system balance.

Objective: We aimed to assess recovery outcomes and neuroimmunological effects of 24-month nVNS on an asplenic participant suffering from RA.

Methods: This study was single subject trial. A man on his 60’s suffering from RA was enrolled and at baseline he was shown how to stimulate remotely at home the auricular branch of the vagus nerve. The primary outcome measure was the change in the simple disease activity index (SDAI), and the secondary outcome measure was the change in the sympathovagal balance (SVB); additionally, we tracked the change in the NIM index across three periods (blocks) with different stimulation settings (20 Hz‒300 μs, 12 Hz‒300 μs and 10 Hz‒300 μs) as another endpoint. Data collection was performed at baseline and every two months during the 24-month run-in period.

Results: Compared with the baseline, the SBV was significantly lower after the first block of treatment (period 1) for a stimulation parameter of 20 Hz–300 μs (p<0.01; p<0.001); the SDAI significantly increased from moderate to high during the last period (p<0.05); and the NIM index only moderately improved during period 1. No other significant improvement was found in the outcomes for the other stimulation parameters during the treatment periods.

Conclusion: Chronic nVNS was safe and well tolerated, but the overall effect of nVNS on an asplenic patient with RA was unremarkable. Our results suggested poor benefits of nVNS on disease activity, the sympathovagal balance and the NIM index after splenectomy. Future controlled trials of nVNS on asplenic subjects are suggested to corroborate our findings.

Clinical Trial Registration: ClinicalTrials.gov NCT07646470.

Keywords: Rheumatoid Arthritis; Splenectomy; Disease Activity; Noninvasive Vagus Nerve Stimulation; Heart Rate Variability; Vagus Nerve

Citation

Pascal J.D. Grolaux. Effects of Chronic Non-Invasive Vagus Nerve Stimulation in an Asplenic Individual with Rheumatoid Arthritis: A Single Subject Trial. WebLog J Med Sci. wjms.2026. g0903. https://doi.org/10.5281/zenodo.21436474