SetPoint VNS for Rheumatoid Arthritis: For Rheumatologists

SetPoint VNS for rheumatoid arthritis: information for rheumatologists.

The FDA approved the SetPoint System (PMA P240039) on July 30, 2025 for adults with moderately to severely active RA who have had an inadequate response, loss of response, or intolerance to one or more biologic or targeted synthetic DMARDs (b/tsDMARDs). The implant is a restricted device sold only to surgeons trained by SetPoint Medical. We place the implant. After recovery the patient returns to the referring rheumatologist, who activates and titrates the device and continues to manage the RA.

Refer a patient →

Mechanism.

SetPoint stimulates the left cervical vagus nerve to activate the inflammatory reflex, a neural circuit that regulates cytokine production. In earlier studies, one minute of vagus nerve stimulation reduced several proinflammatory cytokines by 30 to 70% (Koopman 2016; Genovese 2020).

The device.

• The implant is an integrated neurostimulator about 1 inch (2.5 cm) long and 3 g in weight, seated in a silicone pod on the left cervical vagus nerve. It has no leads and no chest battery pack.

• Stimulation is delivered automatically for 60 seconds once daily. The rheumatologist sets and adjusts therapy with a Bluetooth Programmer.

• The patient recharges the implant with a wireless charger worn around the neck for a few minutes about once a week. The battery is designed to last up to 10 years.

• The implant is MRI conditional. A patient must wait at least two weeks after implantation before an MRI, and MRI personnel must follow the SetPoint MRI safety manual.

RESET-RA.

RESET-RA was a randomized, double blind, sham controlled, multicenter pivotal study at 41 US sites. All 242 patients were implanted and randomized to stimulation (122) or sham (120). The primary endpoint was ACR20 response at week 12. After week 12 the sham group crossed over to stimulation, and all patients entered open label follow-up for 252 weeks. Patients had to remain on a stable csDMARD through week 12. b/tsDMARDs were withdrawn before implantation and not permitted through week 12.

Baseline characteristics: mean age 55.7 years, 86% women, mean RA duration 12.4 years, 53% seropositive, mean DAS28-CRP 5.3, mean CDAI 37.1, mean 14.6 tender and 10.0 swollen joints. Patients had a mean of 2.6 prior b/tsDMARDs (39% had three or more). Prior exposure was 93% anti-TNF, 28% CTLA4-Ig, 23% anti-IL-6, 20% JAK inhibitor, and 14% B cell depleting agents.

Week 12 results (intention to treat).

Open label ACR20 response (patients completing follow-up, both groups on stimulation).

Non augmented patients received no added b/tsDMARD or high dose steroid. Secondary endpoints were not powered for significance. The open label phase has no control group. Benefit accrued slowly over the first 24 weeks, especially in patients with several prior b/tsDMARDs. From week 12 on, adding a b/tsDMARD was permitted for worsening disease.

Safety.

• Vocal cord paresis (4.5%) and dysphonia (2.9%) were reported as resolved within one year. 3 of 243 patients (1.2%) received vocal cord filler injections.

• 94% of patients kept their device (14 of 242 explanted at the time of FDA review).

Patient selection.

Label contraindications. Bilateral or left cervical vagotomy, splenectomy, a pacemaker or defibrillator, neck spine disease that makes intubation unsafe, inability to tolerate anesthesia, and a neck too large to wear the charger.

RESET-RA entry criteria. Age 22 to 75 years, at least 4 of 28 tender and 4 of 28 swollen joints, inadequate response, loss of response, or intolerance to one or more b/tsDMARDs, and a stable csDMARD for at least 4 weeks. Exclusions included current nicotine use, untreated or poorly controlled psychiatric illness, history of substance abuse, significant immunodeficiency, stroke or TIA, clinically significant cardiovascular disease, multiple sclerosis, Alzheimer disease, Parkinson disease, uncontrolled fibromyalgia, prior carotid surgery, recurrent vasovagal syncope, and inability to have an MRI.

What happens after you refer.

1. Referral. Submit the referral form with the patient’s RA history. Patients can also refer themselves.

2. Surgical consultation. We review the history, examine the neck and document baseline voice quality by video, and confirm eligibility.

3. Surgery. The operation is outpatient, takes about 60 to 90 minutes under general anesthesia, and uses a single left neck incision. The closure uses absorbable sutures and skin glue.

4. Activation and titration. The patient returns to the referring rheumatologist 2 to 4 weeks after implant.

5. Follow up. The rheumatologist continues evaluation 3 to 4 times per year for ongoing management.

What to include with a referral.

$1Insurance information and demographics

• RA diagnosis date, serostatus, and disease activity showing moderate to severe (for example RAPID3, CDAI, DAS28)

• Current csDMARD, glucocorticoid, and NSAID doses

• Each prior b/tsDMARD and the rationale for inadequacy: intolerability, adverse events, comorbidities, or inadequate response

• Function (HAQ-DI if available) and current symptoms

• Medical and surgical history, especially head and neck surgery or radiation

• Any pacemaker or defibrillator

• Baseline voice and swallowing

• Allergies, tobacco use, and support at home on the day of surgery

Refer a patient →

Read the patient guide →

Back to overview →

References.

1. Tesser JRP, Crowley AR, Box EJ, et al. Vagus nerve-mediated neuroimmune modulation for rheumatoid arthritis: a pivotal randomized controlled trial (RESET-RA). Nat Med 2026;32:369-378. doi:10.1038/s41591-025-04114-7.
2. SetPoint System Surgeon Instructions for Use, 65154-01 Rev A.
3. US Food and Drug Administration. Premarket approval letter P240039, July 30, 2025.
4. Koopman FA, et al. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci USA 2016;113:8284-8289.
5. Genovese MC, et al. Safety and efficacy of neurostimulation with a miniaturised vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis. Lancet Rheumatol 2020;2:e527-e538.
6. Peterson D, et al. Clinical safety and feasibility of a novel implantable neuroimmune modulation device for the treatment of rheumatoid arthritis. Bioelectron Med 2024;10:8.