Electrical stimulation of the vagus nerve inhibits TNF production and reduces disease activity in patients with active RA, a first-in-human study reports.
In the study published in this week’s PNAS the researchers from the Division of Clinical Immunology & Rheumatology of the Academic Medical Center/University of Amsterdam implanted a stimulation device on the vagus nerve of 17 patients with RA who had active disease.
Participants were studied in two cohorts: cohort I (n = 7) included patients with active disease despite therapy with methotrexate. They had never received a biological TNF antagonist or had previously failed treatment with TNF antagonists.
Cohort II (n = 10) included patients who had failed conventional therapy with methotrexate and with at least two biological agents.
The device was activated and deactivated based on a set schedule to measure response over 84 days, with primary endpoints measured at day 42.
The researchers reported TNF production in cultured peripheral blood obtained from the combined RA study cohort was significantly reduced from baseline measure at day 21 (TNF = 2,900 ± 566 pg/mL on day) to 1,776 ± 342 pg/mL on day 42, (P < 0.05).
DAS28-CRP values went from 6.05 ± 0.18 on day −21 to 4.16 ± 0.39 on day 42, (P < 0.001), when the device was delivering current.
The percentages of patients fulfilling the ACR response criteria for 20%, 50%, and 70% improvement on day 42 were 71.4%, 57.1%, and 28.6%, respectively, for cohort I and 70.0%, 30.0%, and 0.0%, respectively, for cohort II.
The percentages of patients achieving DAS28 remission (DAS28- CRP <2.6) on day 42 in cohorts I and II were 28.6% and 0.0%, respectively.
Improvement was also observed in tender joint count, swollen joint count, patient’s assessment of pain, patient’s global assessment, physician’s global assessment, and CRP.
“Together, these data indicate that vagus nerve stimulation inhibits TNF and significantly attenuates RA disease severity, ” the researchers concluded.
“These findings suggest that it is possible to use mechanism-based neuromodulating devices in the experimental therapy of RA and possibly other autoimmune and autoinflammatory diseases,” they said.
While it was reasonable to consider whether placebo mechanisms contributed to the findings, previous research had reported that biomarkers were not modifiable by placebo effects, the researchers noted.
“This first-in-class study supports a conceptual framework for further studies of electronic medical devices in diseases currently treated with drugs, an approach termed “bioelectronic medicine,” they concluded.
Co-author of the paper Kevin J. Tracey, MD, is a neurosurgeon and president and CEO of the Feinstein Institute for Medical Research, discoverer of the inflammatory reflex and co-founder of SetPoint Medical.