Highlights from

EULAR 2019

European Congress of Rheumatology

Madrid 12-15 June 2019

Stimulation of vagus nerve shows a reduction in rheumatoid arthritis symptoms

Electrical vagus nerve stimulation, could provide a new treatment approach for patients with rheumatoid arthritis (RA). These were the main findings of a non-pharmacological pilot study, presented by Dr Mark Genovese (Stanford University School of Medicine, USA) at EULAR 2019 [1].

Recent advances in neuroimmunology have mapped circuits in the brain that regulate immune responses. In one of the circuits, the ‘inflammatory reflex’, signals are transmitted in the vagus nerve, which inhibits cytokine production including TNF. It is thought that, by stimulating the activity of this inflammatory reflex, innate immune responses can be modulated without abolishing them or producing immunosuppression [2].

In this pilot study, a miniaturised neurostimulator was implanted into 14 RA patients who had failed on at least two biologics (bDMARDs) or targeted oral therapies (JAK inhibitors). All patients remained on a stable background of methotrexate. Patients were randomised to 3 groups who were either placebo, stimulated once daily, or stimulated 4 times a day for 12 weeks. Patients, rheumatologists, joint assessors, and monitors were fully blinded to treatment arm. Clinical efficacy was measured by DAS28-CRP* response and contrast-enhanced MRI (RAMRIS OMERACT). The pharmacodynamic response to vagus nerve stimulation was assessed in blood by measuring cytokines in an ex vivo bioassay.

At the end of the study, the patients who received once-daily stimulation were shown to have a better response than those on 4-times-daily stimulation with two-thirds meeting the EULAR good or moderate response criteria and a mean change in DAS28-CRP* of -1.24. The mean change in DAS28-CRP* in the placebo group was 0.16. The actively stimulated groups showed a decrease of more than 30% in levels of cytokines (IL-1β, IL-6, and TNF-α). Implantation and stimulation were well-tolerated with no device or treatment-related serious adverse events. Two surgery-related adverse events resolved without clinically significant effects.

The pilot study suggests that the neurostimulator reduces RA signs and symptoms. These data support the study of this device in a larger placebo-controlled study as a new treatment approach for RA and possibly other chronic inflammatory diseases.

  1. Genovese M, et al. Abstract LB0009. EULAR 2019

  2. Andersson U, et al. Annu Rev Immunol. 2012; 30:313.

The content and interpretation of these conference highlights are the views and comments of the speakers/authors.