Implanted vagus nerve device shows higher 3-month response than sham in rheumatoid arthritis trial

What was demonstrated
In RESET-RA, a double-blind, sham-controlled trial of 242 adults with rheumatoid arthritis who had an inadequate response to, or intolerance of, biologic or targeted synthetic DMARDs, an implanted device acting on the vagus nerve gave an ACR20 response at 3 months of 35.2% with active stimulation, against 24.2% with sham (P = 0.0209). The primary endpoint was the 3-month ACR20 response. Open-label follow-up, which had no control group, reported ACR20 responses of 50.0% at 6 months and 52.8% at 12 months (all completers). Related serious adverse events occurred in 1.6% of patients, all perioperative and resolved.
Why it matters
This is a pivotal, sham-controlled trial of an implanted vagus nerve device in rheumatoid arthritis. If later trials confirm the benefit, it would support testing this approach in people with rheumatoid arthritis who have not responded adequately to, or cannot tolerate, biologic or targeted synthetic DMARDs.
Caveats
- The 3-month difference from sham was about 11 percentage points (35.2% against 24.2%). About two thirds of patients on active stimulation did not reach an ACR20 response at that point.
- The 6- and 12-month figures come from open-label follow-up with no control group, so they cannot show that stimulation caused the improvement.
- The trial evaluated the SetPoint System, made by SetPoint Medical. The sources checked do not name the trial sponsor, so sponsorship and conflicts of interest need checking against the paper.
- The randomised comparison covers 3 months only, so longer-term control-group evidence is not yet available.
Technology profiles
Sources
- peer reviewed paper
Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial
Tesser JRP, et al.. Nature Medicine, 22 Dec 2025. DOI: 10.1038/s41591-025-04114-7. - news
Vagus nerve stimulator shows ongoing efficacy in rheumatoid arthritis
Rob Volansky. Healio, 4 Feb 2026.
Last reviewed 21 Oct 2026.