Evidence map›Paper›PMID 41071520›Full record

ArticleRheumatology and therapy2025

Neuroimmune Modulation for Drug-Refractory Rheumatoid Arthritis: Long-Term Safety and Efficacy in Patients Enrolled in a Pilot Vagus Nerve Stimulation Study.

Norman B Gaylis, David Sikes, Alan Kivitz, Diane Lewis Horowitz, Melissa Evangelista, Yaakov A Levine, David Chernoff

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Rheumatology and therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07543302 (A Pilot Study to Evaluate Safety and Ability of the Transcutaneous Auricular Vagus Nerve Stimulator the Travagus One System to Decrease Inflammatory Mediators in Patients With Duchenne Muscular Dystrophy.), which is not on this map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07543302 naenrolling by invitationnot on this mapstarted 2026, after this paper: background citation

A Pilot Study to Evaluate Safety and Ability of the Transcutaneous Auricular Vagus Nerve Stimulator the Travagus One System to Decrease Inflammatory Mediators in Patients With Duchenne Muscular Dystrophy.

TypeinterventionalSponsortaVNS ABRan2026 to 2026Enrolled20ConditionsDuchenne Muscular Dystrophy (DMD)ArmsTranscutaneous auricular vagus nerve stimulation
3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Norman B GaylisArthritis and Rheumatic Disease Specialties, Aventura, FL, USA.
David SikesDepartment of Rheumatology, Florida Medical Clinic, Zephyrhills, FL, USA.
Alan KivitzAltoona Center for Clinical Research, Duncansville, PA, USA.
Diane Lewis HorowitzDivision of Rheumatology, Northwell Health, Great Neck, NY, USA.
Melissa EvangelistaSetPoint Medical, Inc., 25101 Rye Canyon Loop, Valencia, CA, 91355, USA.
Yaakov A LevineSetPoint Medical, Inc., 25101 Rye Canyon Loop, Valencia, CA, 91355, USA.
David ChernoffSetPoint Medical, Inc., 25101 Rye Canyon Loop, Valencia, CA, 91355, USA. dchernoff@setpointmedical.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionVagus nerve stimulation activates neuroimmune reflexes that modulate systemic inflammation and may represent a novel non-pharmacologic treatment modality for autoimmune diseases like rheumatoid arthritis (RA). In a 3-month first-in-human, double-blind trial, 50% of patients with drug-refractory RA improved clinically, two patients achieved remission, and pro-inflammatory cytokines declined by 30-50% with daily stimulation. The current study is a 36-month extension of that trial, designed to assess the sustained safety and efficacy of the neuroimmune modulation device in patients with multidrug-refractory RA.

methodsPatients (N = 14) with active RA and prior insufficient response to at least two different biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) with at least two mechanisms of action were implanted with a novel neuroimmune modulation device that stimulates the cervical vagus nerve, treated for 12 weeks, and then assessed for safety and clinical effectiveness in an open-label 36-month extension.

resultsEleven patients completed the extension study through month 36. Patients had previously failed an average of 4.8 different drugs, with 64% (9/14) having failed a tsDMARD before enrolling in the study. The median change in clinical disease activity index (CDAI) score from day 0 to month 36 was - 17.8 (SEM 4.9). At month 36, 64% (7/11) of patients achieved a CDAI response that met or exceeded the minimal clinically important difference. Two of these seven patients were treated with daily stimulation alone, while five patients combined stimulation with an adjunctive b/tsDMARD. No device-related infections, cardiac events, surgical revisions, or device explants were reported. Two adverse events related to the device occurred in a single patient: a mild sore throat and moderate tenderness near the implant site. These events were non-serious, anticipated, and resolved.

conclusionIn this first-in-human long-term extension study, neuroimmune modulation was well tolerated among patients with multidrug-refractory RA, with reductions of clinical disease activity that were maintained through 36 months.

Indexed as

Cholinergic anti-inflammatory pathwayInflammatory reflexNeuroimmune modulationRheumatoid arthritisVagus nerve stimulation

Identifiers

PMID41071520
PMCPMC12638526

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.