Vagus Nerve Stimulation Yields Responses in Refractory Rheumatoid Arthritis

John Tesser, MD

Credit: ACR

Implantation of a vagus nerve stimulation² device was well-tolerated and was effective in adults with active rheumatoid arthritis (RA) disease and inadequate response or intolerance to at least 1 biologic disease-modifying anti-rheumatic drugs (bDMARD) or targeted-synthetic DMARD (tsDMARD).¹

Findings from the phase 3 RESET-RA (NCT04539964) trial evaluating the device were presented at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC, by John Tesser, MD, Adjunct Assistant Professor of Medicine, Midwestern University, and Arizona College of Osteopathic Medicine, and Lecturer, University of Arizona Health Sciences Center, and Arizona Arthritis & Rheumatology Associates.

“If we have a new therapy where [the] safety profile is better, that would be a real game changer for a lot of patients. Now we have to look at longer term data in a lot of patients, but we're hopeful that that will continue, because this is really resetting the neuro immune regulatory system back towards what we hope is the normal balance, and hopefully we don't allow for an over-suppression in that respect,” Tesser told HCPLive® during the meeting.

RESET-RA is a randomized (1:1), double-blind, sham-controlled study that enrolled 242 patients across 41 sites in the United States with moderate to severe RA and inadequate response or intolerance to at least 1 prior b/tsDMARD. Participants remained on stable background conventional DMARDs and were washed off their b/tsDMARD prior to implant procedure. The study became open label after week 12 and control participants crossed over to stimulation, with efficacy assessments repeated for them at week 24. Nonresponders were rescued with steroids or b/tsDMARDs and imputed.

The participants had a mean age of 56 years, RA duration of 12 years, and BMI of 30. They had a mean of 15 tender joints, and 10 swollen joints (28 joint count) and most (86%) were female. Around 1/3 (39%) had 1 prior b/tsDMARD, 22% had 2, and 39% had at least 3 prior b/tsDMARDs. Around half (53%) were seropositive (RF and/or anti-CCP) and mean hsCRP was 8.2 mg/L.¹

Tesser and colleagues found that the stimulation group had significantly higher rates of ACR20 response at week 12 at 35.2% (n = 43/122) compared with 24.2% (n = 29/120) in the control group (P = .0209 [95% CI, 0.6-23.1]). After crossover, ACR20 response improved to 51.5% in the stimulation group and 53.1% in the control group by week 24.¹

Stratifying by prior b/tsDMARd found that those with 1 prior had a 44.2% (n = 23/52) ACR20 response rate in the stimulation group and a 19.0% (n = 8/42) in the control group (P = .0054 [95% CI, 7.1-43.3]). DAS28-CRP LDA/remission rate at Week 12 was also statistically significantly higher in the stimulation group and continued to improve through week 24, and less participants in the stimulation group had erosion progress than in the control group.¹

The implantation had an acceptable safety profile, with a low-rate of related serious adverse events (AEs) in the overall intent-to-treat population. The most related common AE was mild/moderate hoarseness/vocal cord dysfunction. The stimulation therapy specifically was well-tolerated. At Week 24, 81% of patients were on stimulation therapy alone without added b/tsDMARDs, and there were no deaths in the study.¹

“These patients had RA for 13 years. So that was a very long duration of disease in contrast to medicines have been developed over the last number of years where most of those patients after a TNF had been on only 1 TNF, and their duration of disease was more like 8 to 10 years. So, [with] the longer duration of disease, more patients have been on advanced therapies and are more of a harder treatment group to get to success. So, I think it's very important to maintain that context of it,” Tesser said.

REFERENCES

1. Tesser J, June J, Wickersham P, et al. Neuroimmune Modulation in Adults with Rheumatoid Arthritis and Inadequate Response or Intolerance to Biological or Targeted Synthetic DMARDs: Results at 12 and 24 Weeks from a Randomized, Sham-Controlled, Double-Blind Pivotal Study. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L10.

2. Neurostimulation to treat RA. Arthritis Society Canada. Webpage. August 2020. https://arthritis.ca/treatment/emerging-treatment-and-research/neurostimulation#