Stimulating the vagus nerve with an implantable bioelectronic device significantly improved measures of disease activity in patients with rheumatoid arthritis, recently published clinical trial data shows.
Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects 1.3 million people in the United States and costs tens of billions of dollars annually to treat. The findings were announced by the Academic Medical Center/University of Amsterdam, the Feinstein Institute for Medical Research and SetPoint Medical.
The paper highlights a human study designed to reduce symptoms of RA, cytokine levels and inflammation by stimulating the vagus nerve with a small implanted device.
International principal investigator and lead author Professor Paul-Peter Tak, MD, PhD, FMedSci, of the Academic Medical Center/University of Amsterdam, said:
“This is the first study to evaluate whether stimulating the inflammatory reflex directly with an implanted electronic device can treat RA in humans. We have previously shown that targeting the inflammatory reflex may reduce inflammation in animal models and in vitro models of RA.
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."
Vagus nerve stimulation (VNS) therapy, using a pacemaker-like device implanted in the chest, has been used since 1997 to control seizures in epilepsy patients. It has recently also been approved for treating drug-resistant cases of clinical depression. A convenient, non-invasive VNS device that stimulates an afferent branch of the vagus nerve is also being developed and will soon undergo trials.
Anthony Arnold, Chief Executive Officer of SetPoint Medical, said:
“Our findings suggest a new approach to fighting diseases with bioelectronic medicines, which use electrical pulses to treat diseases currently treated with potent and relatively expensive drugs. These results support our ongoing development of bioelectronic medicines designed to improve the lives of people suffering from chronic inflammatory diseases and give healthcare providers new and potentially safer treatment alternatives at a much lower total cost for the healthcare system."
Although it was focused on rheumatoid arthritis, the trial’s results may have implications for patients suffering from other inflammatory diseases, including Crohn’s, Parkinson’s, Alzheimer’s and others.
Co-author Kevin J. Tracey, MD, president and CEO of the Feinstein Institute for Medical Research, discoverer of the inflammatory reflex and co-founder of SetPoint Medical, said:
“This is a real breakthrough in our ability to help people suffering from inflammatory diseases. While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself."
SetPoint is developing a novel proprietary bioelectronic medicine platform to treat a variety of immune-mediated inflammatory diseases, using an implanted device to stimulate the vagus nerve.
Methodology and Results
In the study, a stimulation device was implanted on the vagus nerve during a surgical procedure.
It was then activated and deactivated based on a set schedule to measure response over 84 days, with primary endpoints measured at day 42 using DAS28-CRP. Disease Activity Score 28-CRP is a standard composite score for RA that includes counts of tender and swollen joints, patient’s and physician’s assessment of disease activity and serum C-reactive protein (CRP) levels.
Of 17 patients with active RA in the study, several patients that had failed to respond to multiple therapies, including biologicals with different mechanisms of action, demonstrated robust responses. The findings indicate that active electrical stimulation of the vagus nerve inhibits TNF production in RA patients and significantly attenuates RA disease severity.
Several patients reported significant improvements, including some who had previously failed to respond to any other form of pharmaceutical treatment. In addition, no serious adverse side effects were reported.
The emerging field of bioelectronic medicine aims to target disorders traditionally treated with drugs and instead uses advanced neuromodulation devices that may offer significant advantages.
Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1605635113