Wave nerve stimulation study reveals significant reduction in RA symptoms

The results of one study suggest that electrostimulation of the vagus nerve might constitute a new therapeutic approach for patients with rheumatoid arthritis.¹

"It's a really exciting development. For many patients with rheumatoid arthritis, current treatments do not work or are not tolerated"Said Professor Thomas Dörner, chairman of the scientific program committee, EULAR.

"These results open the door to a new approach to treat not only rheumatoid arthritis, but also other chronic inflammatory diseases. It is certainly a subject to deepen. "

The vagus nerve is the longest and most complex of the 12 pairs of cranial nerves originating from the brain. The name "vague" comes from the Latin word for "wandering". Indeed, the vagus nerve wanders from the brain into the organs of the neck, chest, and abdomen.²

Recent advances in neuroscience and immunology have made it possible to map brain circuits regulating immune responses. In one of the circuits, called "inflammatory reflex", signals are transmitted in the vagus nerve that inhibit the production of cytokines, including tumor necrosis factor (TNF), an inflammatory molecule that is a major therapeutic target for rheumatoid arthritis. rheumatoid. It is thought that by stimulating the activity of this inflammatory reflex, innate immune responses can be modulated without suppressing them or producing significant immunosuppression.³

In this pilot study, a new miniaturized neurostimulator called MicroRegulator was implanted in 14 patients with rheumatoid arthritis who had failed on at least two biological products or targeted oral therapies with different mechanisms of action. Patients were randomized into three groups: placebo, stimulation once a day or four times a day for 12 weeks. At the end of the study, it was shown that patients who received stimulation once a day responded better than those receiving stimulation four times a day, two-thirds meeting the criteria for good or moderate response to stimulation. EULAR and an average change in the rate of DAS28-CRP. -1.24. The mean change in DAS28-CRP in the placebo group was 0.16.¹

Cytokines (a broad and vague category of small proteins important for cell signaling) were also measured in the study; actively stimulated groups showed a more than 30% decrease in interleukin (IL) 1β, IL-6 and TNF-α levels. Implantation and stimulation have generally been well tolerated, with no serious device or treatment-related adverse events, or two surgical-related adverse events resolved without clinically significant effects.¹

"Our pilot study suggests that this new micro-regulator device is well tolerated and reduces the signs and symptoms of rheumatoid arthritis., "Said Mark Genovese, MD, James W. Raitt, professor of medicine, Stanford University, Stanford, California, United States.

"These data support the study of this device as part of a larger placebo-controlled study as a novel therapeutic approach for rheumatoid arthritis and possibly other chronic inflammatory diseases.. "

This study follows a validation study that used reprogrammed vagus nerve stimulators to demonstrate reduced systemic inflammation and improved disease activity in 17 patients with rheumatoid arthritis.⁴

The study included 14 patients with active rheumatoid arthritis who had not responded adequately to more than two biologic disease modifying antirheumatic drugs (bDMARDs) or JAK inhibitors with more than two modes of action. All patients remained on a stable background of methotrexate. The first three patients were implanted and stimulated after three weeks, following the approval of the safety review committee. The remaining 11 patients were implanted and randomized for one minute of stimulation per day, one minute of stimulation four times a day or one minute of placebo stimulation.¹

References

1. Genovese MC et al. First human study of a new vagus nerve stimulation device implanted to treat rheumatoid arthritis. EULAR 2019; Madrid: Summary LB0009.

2. The vagus nerve (CNX). Teach me anatomy. Available at https://teachmeanatomy.info/head/cranial-nerves/vagus-nerve-cn-x/ [Last accessed June 2019].

3. Andersson U, Tracey KJ. Reflex Principles of Immune Homeostasis. Annu Rev Immunol 2012; 30: 313-35.

4. Koopman FA et al. Vagus nerve stimulation inhibits cytokine production and reduces the severity of the disease in rheumatoid arthritis. Proc Natl Acad SciS A., 2016; 113 (29): 8284-9.