• The SetPoint System offers patients with rheumatoid arthritis a non-pharmacotherapeutic option.
• The device can be effective in refractory patients.

HUNTINGTON BEACH, Calif. — Vagus nerve stimulation with the SetPoint System offers a new and promising approach for patients with refractory rheumatoid arthritis, according a speaker at the Congress of Clinical Rheumatology West.

“Vagal nerve stimulation is a new option now proven for patients with RA,” Jeffrey Curtis, MD, MS, MPH, Marguerite Jones Harbert-Gene V. Ball endowed professor of medicine at the University of Alabama at Birmingham, told Healio. “It is the first new mechanism of action that we have had in RA in the last 14 years, since JAK inhibitors. Its excellent safety profile, and potential to combine with other biologics or JAK inhibitors in patients who might do well on both, are particularly unique features of vagal nerve stimulation.”

Curtis first reviewed some of the failed attempts at vagus nerve stimulation in the rheumatology space, from noninvasive devices that were attached to the ear or neck, to those that were embedded directly onto the spleen. The noninvasive devices failed because patients were required to stimulate themselves multiple times a day, creating adherence issues, while the devices in the spleen appeared to have failed from a practical because the surgery was invasive, he said.

Enter the SetPoint System (SetPoint Medical), which was approved for use in rheumatoid arthritis by the FDA in July 2025 in the wake of the RESET-RA study.

According to Curtis, this approach addresses the previous devices’ issues with a 60- to 90-minute outpatient procedure to implant the device in the carotid sheath. The surgery requires a single incision, and once activated it is titrated by a rheumatologist, he said.

The device stimulates the vagus nerve for approximately 1 minute per day, usually in the middle of the night so the patient does not feel it, according to Curtis. An app is used to program it.

Prior to the RESET-RA trial, studies tested more frequent stimulation regimens, along with stimulation for shorter and longer durations than 60 seconds. These strategies showed no additional benefit, according to Curtis.

A rheumatologist manages the patient and use of the device, which requires charging a few minutes each week, Curtis added.

“This is not very invasive nor uncomfortable,” he said.

Vagus nerve stimulation can transiently reduce production of inflammatory cytokines by approximately 30% to 70%, according to Curtis.

“It reduces them transiently,” he said. “It is a Goldilocks effect: Not too little, because then vagus nerve stimulation wouldn’t have an effect, but not too much, because then it would be immunosuppressive.”

This is important because it does not entirely eliminate cytokines that perform other biologic functions, including prevention of infections, Curtis added.

“We do not see the same adverse events in the infection space that we see with some of our patients on biologics or JAK inhibitors,” he said.

Curtis additionally highlighted a few critical components of the RESET-RA trial. He stressed that patients in the cohort had a mean duration of RA for more than 12 years. Meanwhile, nearly half of patients had failed three or more prior therapies, 35% had failed one therapy, and 23% had failed two therapies.

“These people have failed a lot of treatments and were as refractory as any clinical trial population that we’ve ever seen in RA, yet many still responded,” Curtis said.

Another important data point from the RESET-RA results showed that approximately one-quarter of patients augmented the vagus nerve device with a traditional RA therapy within the first 12 months, according to Curtis.

“We never use JAK or TNF inhibitors together,” he said. “It does not help and there are more infections. This is the first study in a very long time where you are combining two targeted therapies.”

The final point Curtis highlighted about RESET-RA was the durability of vagus nerve stimulation in an ongoing, open-label leg of the trial.

“The therapy is increasing in its effectiveness over time,” he said.

The best candidates for vagus nerve stimulation include those who have failed conventional disease-modifying antirheumatic drugs and biologics, according to Curtis. He added that patients who prefer “natural therapies” or those who ask how quickly they can stop taking methotrexate or a biologic may also be inclined to choose this option.

Although patients with higher infection risk or a history of venous thromboembolism might be particularly compelling candidates for vagal nerve stimulation, there are a few caveats, according to Curtis.

“The patient can’t have a pacemaker or an implantable cardioverter-defibrillator, and there is caution with pregnancy,” he said.

Access has also been an issue with the SetPoint device, but Curtis said those concerns are decreasing.

“It is commercially available,” he said. “And Medicare does reimburse this, although access and reimbursement is still variable regionally. Thirty to 40 centers in the United States are doing this now.”

For more information:

Jeffrey Curtis, MD, MS, MPH, can be reached at jrcurtis@uabmc.edu.