Pilot Study Supports Safety of Novel Vagus Nerve Stimulation Device for Refractory RA

human brain and vagus nerve stimulation:VNS, image illustration
human brain and vagus nerve stimulation:VNS, image illustration
Researchers assessed the safety and efficacy of a novel miniaturized vagus nerve stimulation device for the treatment of multidrug-refractory rheumatoid arthritis.

A miniaturized novel vagus nerve stimulation (VNS) device was found to be safe, well tolerated, and showed reduced signs and symptoms in the treatment of refractory rheumatoid arthritis (RA), according to results from a pilot study published in Lancet Rheumatology.

Investigators conducted a 12-week, randomized, multicenter, sham-controlled trial (ClinicalTrials.gov Identifier: NCT03437473) at 5 clinical research sites in the United States. Participants were aged 22 to 75 years and had multidrug-resistant RA. Patients were eligible in the study if they had an insufficient response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and at least 2 biologic or targeted synthetic DMARDs. The MicroRegulator, a wireless, rechargeable neurostimulating device, was implanted on the left cervical vagus nerve of participants. Participants were randomly assigned 1:1:1 to receive active stimulation for 1 minute, once a day; active stimulation for 1 minute, 4 times a day; or sham stimulation (device implanted but not activated). The primary outcome was incidence of treatment-emergent adverse events. The 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) was used to assess clinical improvements. Participants used the devices for 4 days.

A total of 14 patients were enrolled in the study between March and August 2018. Three patients received active stimulation as a preliminary safety assessment (stage 1). After safety review board approval, the VNS device was implanted in the remaining 11 patients (stage 2) who received 1 minute of active stimulation daily (n=3); 1 minute of active stimulation 4 times daily (n=4); or no stimulation (n=4) for 12 weeks. No device- or treatment-related serious adverse events were observed during the study. Surgery-related adverse events were Horner syndrome and vocal cord paralysis, which occurred in 1 patient each. Both of these events resolved without significant sequelae. No deaths occurred.

Among patients who received active stimulation (n=10), 50% had clinical improvement in DAS28-CRP score. Mean changes in DAS28-CRP scores in the stage 1 once-daily, stage 2 once-daily and 4-times-daily groups were -1.4, -1.2, and 0.4, respectively. Four of the 6 patients (67%) who received stimulation once daily exceeded the minimally clinically important difference of -1.2 in DAS28-CRP score.

These preliminary data support the safety and feasibility of the MicroRegulator for symptom management in patients with refractory RA.

“Based on the safety profile observed in this first in-human pilot study, and the risk–benefit profile observed in patients with drug-refractory [RA], these findings will be examined further in a larger efficacy trial,” the investigators concluded.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Genovese MC, Gaylis NB, Sikes D, et al. Safety and efficacy of neurostimulation with a miniaturized vagus nerve stimulation device in patients with multidrug-refractory rheumatoid arthritis: a two-stage multicentre, randomised pilot study. Lancet Rheumatol. Published online July 28, 2020. doi:10.1016/S2665-9913(20)30172-7