ATLANTA — Once-daily vagus nerve stimulation is both safe and well-tolerated in drug refractory patients with rheumatoid arthritis (RA) and successfully reduces signs and symptoms of the disease, according to research results presented at the 2019 American College of Rheumatology/Association of Rheumatology Professionals (ACR/ARP) Annual Meeting, held November 8 to 13, 2019, in Atlanta, Georgia.
Researchers reported safety and efficacy data from a first-in-human, double-blind pilot study of the novel MicroRegulator (MR) miniaturized neurostimulator, used to stimulate the vagus nerve in patients with RA.
Investigators implanted the MR on the left vagus nerve of 14 patients with active RA and prior insufficient response to ≥2 biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors with ≥2 different modes of action. All patients remained on stable background doses of either methotrexate or hydroxychloroquine.
Three weeks after implantation, investigators stimulated the MR in 3 patients, each for 1 minute once daily. After safety approval, the MR was implanted in the remaining 11 patients who were then randomly assigned to receive 1 minute of stimulation either once daily, 4 times daily, or sham treatment for 12 weeks.
Researchers assessed pharmacodynamic response to vagus nerve stimulation by blood cytokine production using an ex vivo bioassay. Clinical efficacy of the treatment was measured by Disease Activity Score in 28 Joints-C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) responses by wrist magnetic resonance imaging (MRI).
Overall, patients tolerated both device implantation and stimulation, with no treatment-related serious adverse events reported, although 2 notable surgical adverse events (left vocal cord paralysis and Horner syndrome) were reported; both adverse events were resolved “without clinically significant sequelae.”
In both groups receiving active stimulation, investigators observed a pharmacodynamic response with a >30% decrease from baseline in bioassay levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. Minimal change was noted in the sham group. In the once-daily stimulation group, 4 of 6 patients had a European League Against Rheumatism good or moderate response, compared with 1 of 4 patients in the 4-times-daily group and none of the patients in the sham group. Both DAS28 and CDAI responses were achieved in 5 of the patients receiving active stimulation; DAS28 remission was achieved in 2 patients. MRI inflammation measures did not change by the end of the study.
“The novel MR device and stimulation was well-tolerated independent of the 2 surgery-related events,” the researchers concluded. “MR-associated [vagus nerve stimulation] reduced signs and symptoms of RA in a meaningful number of highly drug-refractory patients. These initial pilot data support the use of MR for [once-daily vagus nerve stimulation] 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.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Gaylis N, Sikes D, Kivitz A, et al. Neurostimulation for treatment of drug refractory rheumatoid arthritis: a first-in-human study using a novel vagus nerve stimulator. Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. Abstract 930.
This article originally appeared on Rheumatology Advisor