Introduction: Electrical stimulation of the vagus nerve activates innate neuroimmune pathways to downregulate inflammation and restore immunologic balance - providing a novel treatment option for autoimmune diseases like rheumatoid arthritis (RA).
Methods: RESET-RA study (NCT04539964) is a randomized, double-blind, sham-controlled, multi-center trial that evaluated the safety and efficacy of a novel neuroimmune modulation device in adults with moderate-to-severe RA who are incomplete responders or intolerant to one or more biological or targeted synthetic disease modifying anti-rheumatic drugs (b/tsDMARDs).
All patients were washed off their b/tsDMARDs prior to implantation procedure. Miniature integrated neurostimulator was implanted on the left vagus nerve through single incision during an outpatient procedure under general anesthesia. Subjects were randomly assigned (1:1) to receive active or non-active stimulation during programming at the rheumatologist clinic. Safety and efficacy endpoints were assessed through 24 weeks of stimulation.
Results: The study enrolled 242 patients at 41 sites in the U.S. All implant procedures were completed without intraoperative complications or surgical revisions. No unanticipated adverse events (AEs) were reported during the perioperative period. The related serious adverse event (SAE) rate was low (1.7%) through 12 weeks and there were no related SAEs in long-term follow-up, as available. Vocal cord paresis and prolonged hoarseness were the most commonly reported related-AEs. The study met its primary endpoint with a statistically significant greater proportion of study participants achieving American College of Rheumatology 20% response (ACR20) in treatment group compared with control group at 12 weeks (p=0.0209). All secondary and exploratory endpoints, including improvements in disease activity scores and proportion of erosion progressors favored the treatment group. At Week 24, 81% of patients were managed with stimulation therapy, without the addition of steroids or b/tsDMARDs.
Conclusion : Neuroimmune modulation using an implantable device to stimulate the left cervical vagus nerve is well-tolerated and effective in improving signs and symptoms of active RA.
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