Vagus nerve stimulation may benefit patients with RA 'for whom there were no options'
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Daily stimulation of the vagus nerve yielded quantifiable improvement in disease activity in a small cohort of patients with rheumatoid arthritis, bringing this approach closer to becoming a therapeutic reality, according to a presenter at the 2020 Interdisciplinary Autoimmune Summit.
“The question is, what is the molecular basis for this connection between the brain and the peripheral joints and inflammation?” David Chernoff, MD, chief medical officer of SetPoint Medical, and medical consultant at Myriad Genetics in Salt Lake City, Utah, said in his presentation.
Chernoff reviewed the body of basic, translational, preclinical and proof-of-concept research into whether the cholinergic anti-inflammatory pathway could be a method of reducing chronic inflammation. The sum total of research has demonstrated that the inflammatory reflex is a prototypical cholinergic neuro-immune reflex that contributes to immunological homeostasis, according to Chernoff. He added that electrically stimulating the vagus nerve can activate this reflex therapeutically in many rodent models of disease, including RA.
The current pilot study investigated the clinical utility of a daily dose of 60 seconds of vagus nerve stimulation in patients with drug refractory RA. In the study, the device (SetPoint Medical) was successfully implanted into 14 multibiologic refractory RA patients, according to Chernoff. “These are patients that had failed, essentially, all drugs, including janus kinase inhibitors,” he said. “They had long-standing disease. This was a very difficult drug-refractory population for whom there were no options.”
The SetPoint system performed as designed, Chernoff reported, noting that device placement, communication between components, programmability and delivery of stimulation all occurred to the specifications of the designers. The study included a sham group.
Pharmacodynamic data indicated that the mechanism of action performed to specifications, with reduction of proinflammatory cytokines observed for patients treated with active therapy using a validated biomarker assay.
“We observed a meaningful clinical response in treatment groups, with no apparent sham effect,” Chernoff said, reporting that five of 10 patients in treatment groups met or exceeded meaningful clinically important difference (MCID) in disease activity score (DAS) 28-CRP at 12 weeks. “This was surprising, given the drug-refractory nature of the patient population.”
In addition, DAS28-CRP remission was reported in two patients. Moreover, patients in the sham group showed no DAS response.
Trends of joint structure preservation emerged in an MRI analysis. Improvement in rheumatoid arthritis MRI erosion scores correlated with DAS response. Chernoff acknowledged, however, that synovitis and osteitis scores failed to demonstrate a clear conclusion.
The safety profile revealed no device-related adverse events.
Based on these findings, Chernoff reported that further studies are planned.
“Very brief periods of vagus nerve stimulation are sufficient to induce a therapeutic response in half of patients with rheumatoid arthritis, many who had insufficient response to multiple biological drugs,” Chernoff concluded.
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Chernoff D. Bioelectronic Medicine for Treatment of Rheumatoid Arthritis. Presented at: Interdisciplinary Autoimmune Summit; July 10-12, 2020 (virtual meeting).
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