Nerve stimulation reduces severity of rheumatoid arthritis

John Murphy, MDLinx | July 06, 2016

Stimulating the vagus nerve with an implantable bioelectronic device significantly improved measures of disease activity in patients with rheumatoid arthritis (RA), researchers reported July 5, 2016 in the journal PNAS Early Edition.

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Rheumatoid arthritis nerve stimulation device

After researchers implanted this device to electrically stimulate the vagus nerve in patients with rheumatoid arthritis, the patients’ measures of arthritis improved. (Photo: SetPoint Medical)

The researchers had shown in previous studies of animal models and in vitro models of RA that targeting the “inflammatory reflex” reduced inflammation. The inflammatory reflex is defined by signals that travel in the vagus nerve to inhibit monocyte and macrophage production of tumor necrosis factor (TNF) and other inflammatory cytokines.

“This is the first study to evaluate whether stimulating the inflammatory reflex directly with an implanted electronic device can treat RA in humans,” said principal investigator and lead author Paul-Peter Tak, MD, PhD, FMedSci, Professor in the Department of Clinical Immunology & Rheumatology at the Academic Medical Center, University of Amsterdam, in Amsterdam, The Netherlands.

“The direct correlation between vagus nerve stimulation and the suppression of several key cytokines like TNF as well as reduced RA signs and symptoms demonstrates proof of mechanism, which might be relevant for other immune-mediated inflammatory diseases as well,” Dr. Tak explained.

For this study, surgeons implanted a vagus nerve-stimulating device (using a coiled cuff electrode on the left cervical vagus nerve) in 17 patients with active RA. Patients received electric current pulses (up to 2.0 mA maximum) from 0 to 4 times per day, and the researchers measured their responses using a standard disease activity composite score (derived from counting swollen and tender joints, a visual assessment of disease activity, and measures of serum C-reactive protein).

The study included two groups of patients: 7 with moderate RA who had failed methotrexate treatment and 10 with advanced RA who had failed multiple biological disease-modifying anti-rheumatic drugs. In both groups, electrical stimulation of the vagus nerve significantly improved composite scores, while withholding electrical stimulation significantly worsened the severity of disease, the researchers found.

The investigators also noted that significant reductions in TNF release accompanied periods of disease remission while significant increases in TNF release occurred during disease exacerbation.

“Together, these results establish that vagus nerve stimulation targeting the inflammatory reflex modulates TNF production and reduces inflammation in humans,” the authors concluded. “These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases.”

Although this is the first study of nerve stimulation to treat RA in humans, vagus nerve stimulation is not new—it’s been used to treat medically refractory epilepsy in more than 100,000 patients, and it is generally well tolerated, the researchers noted.

SetPoint Medical, manufacturer of the nerve-stimulating device, supported this research.

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