Short-term transcutaneous non-invasive vagus nerve stimulation may reduce disease activity and pro-inflammatory cytokines in rheumatoid arthritis: results of a pilot study

• Published in: Scandinavian journal of rheumatology Vol. 50; no. 1; pp. 20 - 27
• Main Authors: Drewes, AM, Brock, C, Rasmussen, SE, Møller, HJ, Brock, B, Deleuran, BW, Farmer, AD, Pfeiffer-Jensen, M
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.01.2021
• Subjects: Adult; Aged; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - therapy; Electrocardiography; Female; Humans; Interleukin-10 - blood; Male; Middle Aged; Pilot Projects; Proof of Concept Study; Severity of Illness Index; Transcutaneous Electric Nerve Stimulation - statistics & numerical data; Vagus Nerve Stimulation
• ISSN: 0300-9742; 1502-7732
• DOI: 10.1080/03009742.2020.1764617

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA. Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS. Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = −0.37, p = 0.03). Overall, n-VNS was well tolerated. Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.