MADRID — A novel, implantable vagus nerve stimulator can improve symptoms and inflammatory markers in patients with refractory rheumatoid arthritis, a small, first-in-human study suggests.
“We realize there’s an unmet need in rheumatoid arthritis. Despite the many drugs available, we in fact don’t put that many patients into remission,” said Mark Genovese, MD, from Stanford University in Palo Alto, California.
“As this trial shows, there are a fair number of patients with active disease who have failed between three and six biologic therapies,” Genovese told Medscape Medical News. “Over time, it’s become a burgeoning area to use neurostimulation. Whether this becomes an adjunct approach as part of a broader attempt to control rheumatoid arthritis is not clear.”
The vagus nerve — which originates in the brain and stretches into organs in the neck, chest, and abdomen — is believed to be involved in immune response. Previous research has suggested that delivering electrical pulses to the nerve can spark an inflammatory reflex that suppresses a variety of inflammatory cytokines, including tumor necrosis factor (TNF), by 30% to 70%, he explained.
Vagus Nerve and Immune Response
Genovese presented results from the pilot study of the inch-long neurostimulator, known as the microregulator (SetPoint Medical), during a late-breaking clinical trials session here at the European League Against Rheumatism (EULAR) 2019 Congress.
The device was implanted along the vagus nerve in 14 patients with rheumatoid arthritis who had failed at least two biologics or Janus oral kinase (JAK) inhibitors with at least two different mechanisms of action. The device can be recharged wirelessly and programmed by health providers through an iPad app.
The participants, who ranged in age from 22 to 75 years, were all on a stable dose of methotrexate and were randomized to one of three 12-week groups: 60 seconds of stimulation once a day; 60 seconds of stimulation four times a day; or a sham procedure.
After 12 weeks, five of 10 patients in the stimulation groups had a clinically meaningful response, measured by changes in Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP). Two patients achieved DAS28-CRP remission, but there was an “overall lack of DAS response in the sham group,” Genovese reported.
In the stimulation groups, there was also a drop of more than 30% in levels of interleukin (IL)-1-beta, IL-6, and TNF-alpha.
Notably, results were better with once-daily stimulation than with stimulation four times daily.
“We believe the inflammatory reflex is more on–off. Once we turn it on, we believe additional stimulation probably doesn’t make a difference,” Genovese explained. However, “we’re still without a clear explanation why.”
The implantation and stimulation seemed well tolerated overall, and there were no device- or treatment-related serious adverse events. Two patients experienced surgery-related complications, including left vocal cord paralysis and Horner’s syndrome, but they resolved.
Audience members seemed enthusiastic about a technology that could augment treatments for patients with rheumatoid arthritis without the adverse effects of drugs.
Vagus nerve stimulation seems “beneficial,” said John Isaacs, MBBS, PhD, from Newcastle University in Newcastle Upon Tyne, United Kingdom, who is chair of the EULAR abstract selection committee.
He said he is intrigued by the finding that patients stimulated once daily experienced better results than those stimulated four times daily. “In a funny sort of way, it gives you confidence,” Isaacs told Medscape Medical News. “It suggests that one time per day may well be a real result.”
The study was funded by SetPoint Medical. Genovese has received grants from SetPoint and is a consultant for SetPoint. Isaacs is a consultant or has received honoraria and grants for AbbVie, Biogen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Merck, Pfizer, and Roche.
European League Against Rheumatism (EULAR) 2019 Congress: Abstract LB0009. Presented June 15, 2019.