SAT0133 PILOT CLINICAL STUDY OF A NON-INVASIVE AURICULAR VAGUS NERVE STIMULATION DEVICE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: S. Marsal, H. Corominas, M. Lopez Lasanta, D. Reina-Sanz, C. Perez-Garcia, H. Borrell Paños, R. Sanmartí, J. Narváez, C. Franco-Jarava, J. A. Narvaez, J. J. De Agustin, V. Sharma, K. Alataris, M. C. Genovese, M. Baker
Journal: Annals of the Rheumatic Diseases (2020)

Background: Despite the clinical benefit of current pharmacological treatments for rheumatoid arthritis (RA), there remains an unmet need for alternative treatment approaches. Vagus nerve stimulation (VNS) via an implanted device has been shown to attenuate RA disease severity in patients resistant to therapy, 1 as evidenced by a reduction in the DAS28-CRP score following a month of daily stimulation. Objectives: This pilot study investigated the safety and efficacy of a wearable (non-invasive) device that attaches to the outer ear to treat RA via electrical stimulation of the auricular branch of the vagus nerve. Methods: Patients with active RA (≥4 tender/swollen joints based on a 28-joint count, Disease Activity Score-28 with C-reactive protein (DAS28-CRP) &gt;3.8, active synovitis detected on ultrasound and MRI) and inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), or csDMARD and biologic DMARDs (bDMARDs), were enrolled in this open-label study. Patients used the device for up to 30 minutes daily over the course of the 12-week study. The primary endpoint was the change in DAS28-CRP score at Week 12. Secondary endpoints included a safety analysis, proportion of patients achieving ACR20/50/70, the mean change in HAQ-DI and the proportion of patients achieving a HAQ-DI MCID of at least 0.22 over 12 weeks. Additionally, sleep scores were assessed using a visual analogue scale (0-100) at baseline and 12 weeks. Results: Thirty patients with active RA were enrolled, of which 27 patients completed the 12-week protocol. Three patients dropped out of the study: two patients decided to seek other treatment and one patient moved out of the country. Data for three additional patients was not included in this dataset as it was still being collected. Of the 24 patients with complete 12-week datasets, 88% were female, the average age was 54.9 years, mean disease duration was 7.3 years, and four patients had an inadequate response to one or two bDMARDs. The mean change in DAS28-CRP from baseline to Week 12 was -1.43 (p&lt;0.05; Figure 1) and ACR20/50/70 response rates were 58.3%, 37.5%, and 16.7%, respectively (Figure 2). HAQ-DI change from baseline was -0.50 (p&lt;0.05) at 12 weeks, and 15 out of 24 patients achieved an overall HAQ-DI reduction of 0.22 (62.5%). VAS sleep scores were significantly improved over the 12-week study. Scores for trouble falling asleep, awakened by pain at night, and awakened by pain in morning decreased by 64%, 70%, and 60%, respectively (p&lt;0.05, n = 23). Three study adverse events (AEs) were reported: two device related AEs due skin irritation at the earpiece insertion site and one AE due to mucous accumulation in the throat. Figure 1 Figure 2 Average DAS28-CRP is shown for each study visit. Error bars indicate standard error of mean. Percentage of subjects meeting ACR20/50/70 at 12 weeks. Conclusion: In this pilot study, auricular stimulation was well tolerated and daily use over 12 weeks attenuated RA disease severity. Further evaluation in larger controlled studies are needed to confirm whether a non-invasive wearable device might offer an alternative approach for the treatment of RA. References: [1]Koopman FA, et al. (2016) Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Nat Acad Sci 2016; 113: 8284–9. Disclosure of Interests: Sara Marsal: None declared, Héctor Corominas Speakers bureau: Abbvie, Lilly, Pfizer, Roche, Maria Lopez Lasanta: None declared, D Reina-Sanz: None declared, Carolina Perez-Garcia: None declared, Helena Borrell Paños Speakers bureau: Lilly, Novartis, MSD and Janssen, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, J. Narváez: None declared, Clara Franco-Jarava: None declared, Jose Antonio Narvaez: None declared, Juan Jose de Agustin: None declared, Vivek Sharma Shareholder of: Vorso Corp., Konstantinos Alataris Shareholder of: Vorso Corp., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme, Matthew Baker Consultant of: Gilead, Vorso, Paid instructor for: Gilead