Is a vagus nerve stimulator a viable treatment option for rheumatoid arthritis (RA)?

Vagus Nerve Stimulation for Rheumatoid Arthritis: Not Currently Recommended

Vagus nerve stimulation is not currently recommended as a viable treatment option for rheumatoid arthritis as it is not FDA-approved for this indication and lacks sufficient evidence of efficacy. 1

Current Status and Evidence

The American College of Rheumatology (ACR) explicitly states in their 2022 guidelines that no recommendation was made regarding vagus nerve stimulation for RA because this invasive procedure is not currently approved by the FDA for rheumatoid arthritis. 1

Recent clinical trials investigating vagus nerve stimulation for RA have shown mixed results:

• A 2023 randomized, double-blind, sham-controlled trial of auricular vagus nerve stimulation found no meaningful improvement in RA disease activity. The primary endpoint (ACR20 response) showed no significant difference between active stimulation (25.0%) and sham (26.9%). 2

• A 2021 proof-of-concept study using non-invasive vagus nerve stimulation showed some promising results with mean DAS28-CRP reduction of -1.4 and 37% of patients reaching DAS28-CRP ≤3.2. However, this was an uncontrolled, open-label study with only 30 participants. 3

• A 2020 two-stage pilot study using a miniaturized VNS device reported that VNS was safe and reduced signs and symptoms of RA in multidrug-refractory patients, but this was a very small study. 4

• A 2024 safety and feasibility study (RESET-RA) demonstrated that surgical procedures for implantation of a neuroimmune modulation device were safe, but efficacy data was not reported in this interim analysis. 5

Potential Risks and Considerations

Implantable vagus nerve stimulation devices carry risks that must be considered:

• Surgical complications have been documented, including vocal cord paresis and prolonged hoarseness 5
• Horner's syndrome and vocal cord paralysis have been reported as surgery-related adverse events 4

Current Treatment Recommendations for RA

The ACR guidelines recommend several other integrative approaches for RA management that have better evidence:

• Conditionally recommended: acupuncture, massage therapy, and thermal modalities 1
• Conditionally recommended against: electrotherapy (including TENS) and chiropractic therapy 1

Clinical Decision Algorithm

For patients inquiring about vagus nerve stimulation for RA:

1. Explain that VNS is not FDA-approved for RA and is not recommended in current treatment guidelines

2. Ensure the patient is optimized on standard RA therapies:

   • Disease-modifying antirheumatic drugs (DMARDs)
   • Biologic agents if indicated
   • Treat-to-target approach as recommended by ACR

3. If the patient is interested in complementary approaches, consider ACR-recommended options:

   • Thermal modalities (heat, cold therapy)
   • Massage therapy by providers experienced with RA
   • Acupuncture (though considered lower value by patient panels)

4. For patients with refractory disease interested in VNS:

   • Discuss the limited and mixed evidence for efficacy
   • Explain potential surgical risks
   • Consider referral to clinical trials investigating VNS for RA if available

Conclusion

While research into vagus nerve stimulation for RA continues, with some early studies showing potential, the current evidence does not support its use outside of clinical trials. The ACR guidelines make no recommendation for VNS due to lack of FDA approval, and the most recent high-quality randomized controlled trial showed no significant benefit over sham treatment.