Innovative Neuroimmune Modulation with the SetPoint System in Rheumatoid Arthritis: Insights from the RESET-RA Study

RESET-RA found the implantable SetPoint System produced durable, clinically meaningful improvement in adults with moderately-to-severely active rheumatoid arthritis—marking a move toward targeted neuroimmune modulation without broad systemic immunosuppression.

RESET-RA is a pivotal, double-blind, randomized, sham-controlled trial that assessed primary endpoints including ACR20 response and composite disease-activity measures. It reported a statistically significant ACR20 improvement at three months (p = 0.0209) and an open-label 12-month ACR20 response rate of 52.8%.

Disease-activity measures reinforced the primary signal: by 12 months, 49.3% of treated patients achieved DAS28-CRP low disease activity or remission and 47.4% reached CDAI low disease activity or remission—shifts in joint counts and inflammatory markers that are clinically meaningful at the patient level. Nearly half of participants maintained these benefits at one year, suggesting sustained disease control without adding biologic DMARDs or JAK inhibitors for most patients.

Safety through 12 months was favorable. There were no related deaths or unanticipated adverse device effects, and no new serious device-related adverse events identified during protocolized monitoring. The majority of adverse events were comparable across arms during the controlled period; related serious adverse events were perioperative (1.6%) and resolved. Perioperative events were infrequent and transient, supporting a risk–benefit profile that may favor the device for appropriately selected patients.

Key Takeaways:

• RESET-RA reported a statistically significant ACR20 improvement at 3 months with sustained response through 12 months and a 77.3% EULAR good/moderate response at one year.
• Nearly half of patients achieved DAS28-CRP low disease activity or remission (49.3%) and CDAI low disease activity or remission (47.4%) at 12 months, indicating meaningful patient-level improvements.
• No new serious device-related adverse events were identified through 12 months; perioperative serious adverse events were infrequent (1.6%) and resolved, supporting a favorable safety profile.