Optimism for vagus nerve stimulation in RA

4 minute read

While a recent study into wearable vagus nerve stimulators didn’t prove fruitful, US expert remains hopeful for implantable devices.

Two studies presented at this year’s ACR 2023 Convergence on the role of the vagus nerve in rheumatoid arthritis were seemingly at odds.  

But Dr Matthew Baker from Stanford University, who presented both studies, remained confident that there was a place for vagus nerve stimulation in RA care. 

In recent years, growing research has explored the role of the vagus nerve in inflammatory disorders, such as rheumatoid arthritis, as stimulation of the nerve has been demonstrated to interrupt the inflammatory reflex, ultimately supressing inflammatory cytokine production by macrophages. 

While some studies have shown reduction in RA symptoms through vagus nerve stimulation, the jury is still out as the studies have been small and often without control group.  

Speaking at this year’s ACR 2023 convergence, Dr Baker said his research group hoped to explore the role of the vagus nerve in RA from the “other side” by interrupting vagus nerve signalling through a vagotomy.  

The team explored the effects of two types of vagotomy on both RA, which is an inflammatory disorder and OA, which is a far less inflammatory disorder, Dr Baker said. 

In his presentation, Dr Baker said the group expected that full truncal vagotomy, which supressed all signalling of the vagus nerve to distal sites, would increase the risk of RA without impacting development of OA.   

The researchers expected the second type of vagotomy, superselective vagotomy which only affects signalling to the stomach, would have no effect on either disorder. 

The population-based cohort study in Denmark used Danish National Patient Registry and Danish Civil Registration System data collected between 1977 and 1995. 

The research group studied the incidence of RA, OA and incidence of joint replacement with OA in 2260 patients who underwent truncal vagotomy compared to 22610 controls, and in 3810 superselective vagotomy patients compared to 38090 comparators. 

The researchers found that patients with a truncal vagotomy were more than twice as likely to develop RA compared to their matched controls (hazard ratio 2.62), meaning truncal vagotomy was associated with an increased risk of RA. 

But, as expected, risk of OA was not affected by truncal vagotomy: the hazard ratio was 1.23 for OA and 0.73 for OA with joint replacement, both non-significant. 

For patients with a superselective vagotomy, there was no difference seen in the risk of RA or OA.  The hazard ratio for developing RA was 1.05 compared to the control cohort, 1.01 for OA and 0.73 for OA and joint replacement. 

“These results support the hypothesis that disruption of vagus nerve signalling may contribute to the development of RA,” the researchers said. 

Dr Baker also presented on another study he led into vagus nerve stimulation. 

In this randomised, double-blind, sham-controlled trial, patients aged 18-75 years old with active RA who were unresponsive to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and naïve to biological or targeted synthetic DMARDs received a wearable auricular vagus nerve stimulator. 

Patients were randomised to receive either unilateral 20 kHz stimulation (113 patients) or sham (101 patients) over 12 weeks and were instructed to use the device for 15 minutes a day, Dr Baker said. 

The researchers concluded that auricular VNS was “safe and well tolerated, but it did not meaningfully improve RA disease activity”. 

“More large, controlled studies of VNS for the treatment of RA are needed to better understand its potential future role,” Dr Baker told the delegates. 

“I’m still optimistic that vagus nerve stimulation will have a role and have a positive benefit in patients with RA. 

“All we can conclude with this study is that this particular device, which uses very specific stimulation parameters, and is pretty distant from the nerve itself, did not work.” 

Dr Baker concluded that he was hopeful that implanted vagus nerve stimulation devices would provide benefit. 

  • 0836 Vagotomy and subsequent risk of rheumatoid arthritis and osteoarthritis: a danish register-based cohort study 
  • 0837 A randomized, double-blind, sham-controlled, clinical trial of auricular vagus nerve stimulation for the treatment of active rheumatoid arthritis 

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