during a brief pilot trial.
“Our study population included individuals with significant pain and exemplifies the unmet need for adequate control of pain and fatigue in SLE. Importantly, this was a double-blind, sham-controlled study and neither the subject nor assessor was aware of a subject’s intervention. Objective outcomes, that is, tender and swollen joint counts, were also significantly reduced in subjects receiving taVNS, compared with those receiving [sham stimulation]. The stimulation was well tolerated with no adverse events attributed to the intervention, and, clinical benefits continued after taVNS was stopped,” first author Cynthia Aranow, MD, and her colleagues at the Feinstein Institutes for Medical Research in Manhasset, N.Y., wrote in Annals of the Rheumatic Diseases.
Stimulation of the vagus nerve can be achieved through the ear via its auricular branch, which innervates the cymba concha in the outer ear. Past pilot studies of implanted VNS devices lasting 6 weeks to 6 months in patients with Crohn’s disease or rheumatoid arthritis have shown improvements in measures of disease activity as well as objective markers of inflammation, and a more recent trial testing a transcutaneous devices’s effect in patients with Sjögren’s syndrome found significant reductions in fatigue over a 26-day period, the investigators noted.
In the taVNS device study, the researchers recruited 18 patients with SLE who had musculoskeletal pain rated as 4 or higher on a 10-cm visual analog scale and randomized them in a 2:1 ratio to receive taVNS once per day for 5 minutes for 4 consecutive days versus sham stimulation. Patients were allowed to be on stable doses of disease-modifying antirheumatic drugs, biologics, and/or prednisone ≤ 10 mg/day, with no change of dose within 28 days prior to baseline. The study excluded patients who used tobacco or an anticholinergic medication and those with a diagnosis of fibromyalgia.
The 12 patients who received actual taVNS had a significantly greater reduction in their pain, compared with 6 sham-treated patients (–5.00 vs. 0.10; P = .049), with 10 of 12 and 1 of 6 having a clinical response (a reduction of at least 1.58 on a 10-cm visual analog scale from baseline to day 5). Stimulation-treated patients also reported significantly greater reductions in fatigue, with 10 of 12 achieving a meaningful reduction, defined as a 4-point improvement on the Functional Assessment of Chronic Illness Therapy Fatigue Subscale; none of the sham-treated patients experienced meaningful improvement of fatigue. The patients who received taVNS had resolution of all swollen and tender joints, compared with 5.3% of tender and 9.1% of swollen joints in sham-treated patients. Ex vivo lipopolysaccharide stimulation of whole-blood samples from taVNS-treated patients, however, showed no reductions of inflammatory mediators or chemokines in tests on day 5 and day 12.
The investigators reported that there were no adverse events attributed to taVNS, including no reports of headache, lightheadedness, tinnitus, ear irritation, or changes to the external skin of the outer ear.
The study was supported by a grant from the John and Marcia Goldman Foundation. One author reported a financial relationship with Set Point Medical and My String, and three authors reported having a provisional patent application titled “Auricular stimulation device, system and methods of use.”
SOURCE: Aranow C et al. Ann Rheum Dis. 2020 Nov 3. doi: 10.1136/annrheumdis-2020-217872.