Rheumatoid Arthritis

Novel Stimulation Device May Reduce Rheumatoid Arthritis Symptoms

Stimulation from a novel miniaturized neurostimulator can reduce signs and symptoms of rheumatoid arthritis (RA) among individuals with highly refractory disease, according to research that will be presented at the 2019 Annual European Congress of Rheumatology.

Previous research has shown that electrical vagus nerve stimulation (VNS) reduced systemic inflammation and improved disease activity among individuals with RA.


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For this double-blind study, the researchers developed the MicroRegulator (MR) and sought to assess safety and efficacy among 14 individuals with RA who had a prior insufficient response to biological disease-modifying antirheumatic drugs or janus kinase inhibitors.

The researchers implanted the MR in 14 participants. Three weeks after the implantation, 3 participants underwent a 1-minute stimulation once daily. After safety approval, the researchers randomly assigned the remaining 11 participants to either 1-minute stimulation once daily, 4 daily 1-minute stimulations, or 1-minute sham treatments for 12 weeks.

Participants who were initially assigned to sham treatment had their devices activated after the primary endpoint at 12 weeks. Clinical efficacy was measured via Disease Activity Score 28 using C-reactive protein (DAS28-CRP) response and contrast-enhanced magnetic resonance imaging.

No device or treatment-related serious adverse effects were observed. There were 2 surgery-related adverse events—left vocal cord paralysis and Horner syndrome—that resolved.

On average, participants in the open-label and once-daily stimulation groups had a decrease in DAS28-CRP scores at 12 weeks, which corresponded with better RA control. Participants in the sham group and those who received 4 daily stimulations had modest increases in average DAS28-CRP scores, which suggested worse RA control.

Among participants who were stimulated once daily, 4 of 6 had a good or moderate response according to European League Against Rheumatism (EULAR) criteria. Scores from the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system correlated with the EULAR responses.

The pharmacodynamic response to VNS was confirmed in the actively stimulated groups, with a more than 30% decrease in bioassay levels of interleukin 1β, interleukin 6, and tumor necrosis factor α from baseline to 12 weeks.

Synovitis or osteitis, based on MRI findings, had not changed after 12 weeks of stimulation.

“These initial pilot data support the use of the MR in a larger blinded sham-controlled study in patients who have failed biologics or targeted oral therapies as a novel approach for treatment of RA and other chronic inflammatory diseases,” the researchers concluded.

—Melinda Stevens

Reference:

Genovese MC, Gaylis N, Sikes D, et al. First-in-human study of novel implanted vagus nerve stimulation device to treat rheumatoid arthritis [EULAR LB0009]. Ann Rheum Dis. 2019;78(suppl 2):A264. http://scientific.sparx-ip.net/archiveeular/index.cfm?searchfor=LB0009&view=1&c=a&item=2019LB0009. Accessed June 10, 2019.