Electrical Stimulation Could Alleviate Rheumatoid Arthritis

A new study suggests that electrical stimulation of the vagus nerve could attenuate disease severity in rheumatoid arthritis (RA) by blocking the production of inflammatory cytokines.

Researchers at the University of Amsterdam Academic Medical Center (AMC; The Netherlands), the Feinstein Institute for Medical Research (Manhasset, NY, USA), and other institutions conducted a study of 17 patients with active RA (mean age 51, 75% female) who had at least four tender and swollen joints, despite methotrexate treatment. The patients were divided into a cohort of seven patients who had never received a tumor necrosis factor (TNF) inhibitor, and a cohort of 10 patients who had been treated unsuccessfully with at least two different types of biologic agents.


Surgical implantation of the neuromodulation device took place on day −14, and from that day to day 0, the device was turned off. On day 0, patients received a single 60-second electric current pulse of 250 µs duration, 10 Hz, output current of 0.25 to 2 mA, as tolerated. No additional stimulations were given for the next week. On day 7, the current was adjusted to the highest level tolerated (up to 2 mA), delivered once per day for 60 seconds, with 250 µs pulse widths and at 10 Hz. At day 28, patients who had not achieved a good or moderate response could have the stimulation frequency increased up to four times per day.

The results showed that the production of TNF decreased from 2,900 pg/mL on day −21 to 1,776 pg/mL on day 42, when the stimulator was turned off for 14 days. By day 56, TNF levels had increased again to 2,617 pg/mL. At day 56 the stimulator was turned on again and patients were followed until day 84, at which time TNF levels had once again fallen, to 1,975 pg/mL. The researchers also found that mean disease activity scores in 28 joints (DAS28) fell from 6.05 to 4.16 by day 42, rose to 4.96 by day 56, but then decreased after stimulation was reinstated.

Overall, DAS28 remission, defined as a score below 2.6, was seen in 28.6% of the first cohort, but in none of the patients in the second cohort. Improvements were also seen in the individual components of the DAS28, including tender and swollen joint counts, patient's pain rating, and patient and physician global assessments. The study was published on July 19, 2016, in Proceedings of the National Academy of Sciences (PNAS).

“Vagus nerve stimulation in RA patients significantly inhibited TNF production for up to 84 days. Moreover, RA disease severity, as measured by standardized clinical composite scores, improved significantly,” concluded senior author Paul-Peter Tak, MD, PhD, of the AMC, and colleagues. “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.”

For the study, the researchers used the Cyberonics (Houston, TX, USA) vagus nerve-stimulation (VNS) system, originally developed for the treatment of epilepsy, which consists of a titanium-encased generator with a lithium battery to fuel the generator, a lead system with electrodes, and an a helical anchor tether wrapped around the cervical vagus nerve. The lead itself was tunneled subcutaneously from the neck to the pulse generator and inserted into the lead attachment port on the generator.

Related Links:
University of Amsterdam Academic Medical Center
Feinstein Institute for Medical Research
Cyberonics