Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study

Marsal, Sara; Corominas, H.; Agustín, Juan José de; Pérez-García, Carolina; López-Lasanta, María; Borrell, Helena; Reina, Dèlia; Sanmartí, Raimón; Narváez, Javier; Franco-Jarava, Clara; Peterfy, Charles; Narváez, José Antonio; Sharma, Vivek; Alataris, Konstantinos; Genovese, Mark C.; Baker, Matthew

doi:10.1016/s2665-9913(20)30425-2

Cited by 42 publications

(54 citation statements)

References 24 publications

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“…The second was a two-stage pilot study utilising VNS in 14 RA patients which demonstrated significant improvements in clinical and biochemical domains whereas those using a sham device did not (48). The most recent single-arm proof-of-concept study demonstrated a significant reduction in DAS28-CRP in 30 patients with RA refractory to biological therapies over 12 weeks (49). Several small studies which have used VNS have suggested an improvement in symptoms in a wide range of conditions including migraine, anxiety, depression, and fibromyalgia (50)(51)(52)(53).…”

Section: Ans As a Potential Therapeutic Targetmentioning

confidence: 99%

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Autonomic Nervous System Dysfunction in Primary Sjögren’s Syndrome

Davies

2021

Front. Immunol.

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Primary Sjögren’s syndrome (pSS) is an autoimmune disease which primarily affects the exocrine glands, but can also affect other organs, including the nervous system. Many studies have reported evidence of autonomic nervous system (ANS) dysfunction in pSS which may contribute to a wide range of symptoms and functional burden. Symptoms of ANS dysfunction are common and widespread among patients with pSS and are associated with other features of the disease, particularly fatigue. Accumulating data on the inter-relationship between the ANS and the immune system via the vagus nerve have been reported. Vagus nerve stimulation (VNS) has also been associated with improvement in fatigue in patients with pSS. Taken together, these data suggest that the ANS may be a potential treatment target for pSS, in particularly those with fatigue being a predominant symptom. Future research to dissect the link between the ANS, immune dysregulation and clinical manifestations in pSS and to evaluate the potential of VNS as a therapy for pSS is warranted.

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Section: Ans As a Potential Therapeutic Targetmentioning

confidence: 99%

“…In rheumatoid arthritis (RA), three small studies have shown clinical and biochemical benefit when using VNS ( 46 , 48 , 49 ). The first of these studies was an open-label trial of 18 RA patients unresponsive or intolerant to conventional and biological therapies.…”

Section: Ans As a Potential Therapeutic Targetmentioning

confidence: 99%

Autonomic Nervous System Dysfunction in Primary Sjögren’s Syndrome

Davies

2021

Front. Immunol.

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“…The goal of this study was to determine whether a single course of taVNS with duration similar to that of the daily dose employed in [8] could lead to detectable changes in CBF.…”

Section: Introductionmentioning

confidence: 99%

“…The theory behind the therapeutic efficacy of taVNS is that stimulating the vagus nerve can correct maladaptive processing within the nervous system as well as neuro-immune communications that are associated with negative health outcomes. Building upon prior work that suggests a link between ANS dysfunction and inflammation [7], a recent open-label study of subjects with rheumatoid arthritis demonstrated clinically relevant changes in both disease biomarkers and symptoms after 12 weeks of sub-threshold taVNS treatment [8]. The therapeutic benefits of taVNS have also been reported in the context of depression [1,7,9] and migraine [10], with mounting evidence linking these clinical effects to neural responses [2,3,11].…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, no studies to date have examined the CBF response to taVNS. In this study, we used arterial spin labeling (ASL) MRI to measure changes in CBF induced by 15 minutes of taVNS in healthy subjects, employing a stimulus similar to that of [8]. In contrast to SPECT and PET, ASL MRI does not require the injection of radioactive tracers, making it especially suitable for repeated measures in a healthy population [25,26].…”

Section: Introductionmentioning

confidence: 99%

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Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow

Mao

Falahpour

et al. 2021

Preprint

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Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has shown promise as a non-invasive alternative to vagus nerve stimulation (VNS) with implantable devices, which has been used to treat drug-resistant epilepsy and treatment-resistant depression. Prior work has used functional MRI to investigate the brain response to taVNS, and more recent work has also demonstrated potential therapeutic effects of high-frequency sub-threshold taVNS in rheumatoid arthritis. However, no studies to date have measured the effects of high-frequency sub-threshold taVNS on cerebral blood flow (CBF). Objective/Hypothesis: The objective of this study was to determine whether high-frequency (20 kHz) sub-threshold taVNS induces significant changes in CBF. Methods: Arterial spin labeling (ASL) MRI scans were performed on 20 healthy subjects in a single-blind placebo-controlled repeated measures experimental design. The ASL scans were performed before and after 15 minutes of either sub-threshold taVNS treatment or a sham control. Results: taVNS induced significant changes in CBF in the superior posterior cerebellum that were largely localized to bilateral Crus I and Crus II. Post hoc analyses showed that the changes were driven by a treatment-related decrease in CBF. Conclusions: Fifteen minutes of high-frequency sub-threshold taVNS can induce sustained CBF decreases in the bilateral posterior cerebellum in a cohort of healthy subjects. This study lays the foundation for future studies in clinical popluations to assess whether similar effects can be observed and are related to treatment outcomes.

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A Randomized, Double‐Blind, Sham‐Controlled, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis

Baker

Kavanagh

Cohen

et al. 2023

Arthritis & Rheumatology

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ObjectivePreliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA), however prior studies have been small and/or uncontrolled; this study aimed to address that gap.MethodsThis randomized, double‐blind, sham‐controlled trial enrolled patients aged 18‐75 years with active RA who had failed conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C‐reactive protein (DAS28‐CRP) and Health Assessment Questionnaire‐Disability Index (HAQ‐DI).ResultsA total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation vs 26.9% for sham (difference vs sham [95% CI]: ‐1.9 [‐18.8‐14.9], p=0.823). The least square mean (SE) change in DAS28‐CRP was –0.95 (0.16) for active stimulation and –0.66 (0.16) for sham (p=0.201); in HAQ‐DI it was –0.19 (0.06) for active stimulation and –0.02 (0.06) for sham (p=0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate.ConclusionAuricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility.This article is protected by copyright. All rights reserved.

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Non-invasive vagus nerve stimulation for rheumatoid arthritis: a proof-of-concept study

Cited by 42 publications

References 24 publications

Autonomic Nervous System Dysfunction in Primary Sjögren’s Syndrome

Autonomic Nervous System Dysfunction in Primary Sjögren’s Syndrome

Effects of sub-threshold transcutaneous auricular vagus nerve stimulation on cerebral blood flow

A Randomized, Double‐Blind, Sham‐Controlled, Clinical Trial of Auricular Vagus Nerve Stimulation for the Treatment of Active Rheumatoid Arthritis

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