Neuroimmune Modulation Shows Promise in Treating Moderate-to-Severe Rheumatoid Arthritis

In a step forward for rheumatoid arthritis (RA) treatment, SetPoint Medical has announced promising results from its RESET-RA study, which were presented at the American College of Rheumatology (ACR) Convergence 2024. The trial highlights the potential of the SetPoint System, a neuroimmune modulation device, as a first-of-its-kind treatment for adults with moderate-to-severe RA who have not responded adequately or are intolerant to biologic or targeted synthetic DMARDs (b/tsDMARDs).

Key Findings From the RESET-RA Study

The RESET-RA trial enrolled 242 participants and demonstrated that the SetPoint System met its primary efficacy endpoint, achieving a significant ACR20 response at 12 weeks. Patients treated with the device showed a 35.2% ACR20 response rate compared to 24.2% in the sham control group (p=0.0209). Among patients with exposure to only one prior b/tsDMARD, the ACR20 response was even higher, with 44.2% responding to SetPoint therapy compared to just 19.0% in the control group (p=0.0054).

The study also reported improvements in Disease Activity Score (DAS28-CRP), with significantly more patients achieving low disease activity or remission in the treatment group at 12 weeks (p=0.0154). Additionally, MRI results revealed a substantial reduction in bone erosion progression, particularly in patients with a highly erosive phenotype, where erosion rates were halved compared to the control group (p=0.016). Importantly, by Week 24, 81% of patients were managed solely on SetPoint therapy without requiring adjunctive steroids or additional b/tsDMARDs.

Why These Results Matter

RA affects over 1.5 million adults in the U.S., and current treatments often leave gaps in effectiveness or pose significant safety risks. The SetPoint System, an implantable vagus nerve stimulation device, offers a novel mechanism of action by activating innate anti-inflammatory pathways without the immunosuppressive side effects seen with many drug therapies.

“The results from the RESET-RA study... underpin the continued positive clinical impact of neuroimmune modulation as a potential novel treatment for rheumatoid arthritis,” said John Tesser, MD, the study's principal investigator. Additionally, the low rates of serious adverse events (1.7%) and the absence of study discontinuations due to side effects further emphasize the system’s potential as a safe and well-tolerated option.

The innovative design of the SetPoint System, which automates daily nerve stimulation after a one-time outpatient implantation procedure, addresses common adherence challenges faced with traditional RA therapies. As David Chernoff, MD, Chief Medical Officer of SetPoint Medical, noted, “RESET-RA is the first randomized, sham-controlled trial to positively demonstrate the clinical potential of neuroimmune modulation for the treatment of RA.”

Looking Ahead

These findings represent a promising advance in RA management, especially for patients with difficult-to-treat disease. While long-term data are needed to confirm these results, the SetPoint System could become a game-changer in the treatment landscape, offering a potentially safer, drug-free alternative for managing RA and other autoimmune conditions.

Further research is anticipated to expand on these initial findings and explore the system’s utility in broader patient populations, including those with other chronic inflammatory diseases.