AURICULAR TRANSCUTANEOUS HI-FREQUENCY E-MMUNOTHERAPY SEQUENCES (ATHENS) FOR THE TREATMENT OF RHEUMATOID ARTHRITIS: 1-YEAR CHANGES IN SYNOVITIS, OSTEITIS, AND BONE EROSION

Background: Current pharmacological treatments remain inadequate for a significant proportion of patients with rheumatoid arthritis (RA), and thus alternative treatment approaches are needed. Prior results from the first 12 weeks of a proof-of-concept (POC) study showed that ATHENS, a non-invasive high-frequency vagus nerve therapy, was well-tolerated with meaningful reductions in RA disease severity as measured by the American College of Rheumatology response criteria (ACR) and the Disease Activity Score using 28 joints (DAS28)[1]. Objectives: The current analysis assessed long-term changes (52 weeks total follow-up) in disease activity as measured by ACR, DAS28, and the following MRI-assessed changes: synovitis, osteitis, bone erosion, and cartilage loss. Methods: Following the completion of the 12-week POC study, patients achieving a reduction in DAS28-CRP of ≥1.2 were given the option to enroll in the 9-month open-label extension (OLE) study. During the extension phase, patients were to use the wearable device for 15 minutes per day. Adjustment of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic disease-modifying antirheumatic drugs (bDMARDs) were allowed during the OLE. Changes from baseline were assessed at 12 weeks (end of initial POC) and 52 weeks (end of the OLE). Structural damage and disease progression were evaluated by standardized MRI of the wrist and hand, with and without intravenous gadolinium-based contrast. MRIs were evaluated by two independent, central readers, blinded to clinical information and visit-order of the images, and were scored for synovitis, osteitis and bone erosion using the OMERACT-RAMRIS method. Cartilage loss was also determined using the 9-point cartilage loss scale (CARLOS). Results: Twenty-seven of 30 patients completed the initial 12-week study, of whom 19 consented and entered the OLE. Of those 19 patients, 4 (21%) discontinued due to lack of efficacy, while the remaining 15 completed the 9-month extension. Due to the COVID-19 pandemic, 7 patients were unable to complete a 52-week MRI scan; MRI evaluations at baseline, 12 weeks, and 52 weeks were available for 8 patients. DAS28-CRP mean (standard deviation [SD]) change from baseline was -1.78 (1.01) at 12 weeks (n=19; p<0.0001) and -2.30 (1.22) at 52 weeks (n=15; p<0.0001). ACR20, ACR50, and ACR70 response rates were 68%, 42%, and 21% at 52 weeks (n=19; discontinued participants were deemed non-responders). MRI analysis of synovitis, osteitis, bone erosion, and cartilage loss showed no evidence of disease progression through 52 weeks compared with baseline ( Table 1 ). Table 1. Change in MRI OMERACT-RAMRIS from baseline to week 52 Score Baseline (n=8) Week 12 (n=8) Week 52 (n=8) Change Week 12 vs BL (n=8) Change Week 52 vs BL (n=8) CARLOS, mean (SD) 3.9 (5.6) 3.9 (5.6) 3.9 (5.6) 0.0 (0.0) 0.0 (0.0) Erosion, mean (SD) 10.8 (10.3) 10.5 (10.3) 10.6 (10.3) -0.3 (0.4) -0.1 (0.8) Osteitis, mean (SD) 2.8 (4.1) 2.3 (3.7) 1.0 (1.1) -0.5 (1.1) -1.8 (3.1) Synovitis, mean (SD) 4.0 (4.2) 4.1 (4.7) 3.3 (4.0) 0.1 (0.6) -0.7 (1.0) CARLOS = Cartilage loss score; OMERACT = Outcome Measures in Rheumatology; RAMRIS = Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System During the 9-month extension study, two new adverse events were reported (cornea transplant and right hand dysesthesia) in 2 (11%) patients; neither was treatment-related and both resolved without intervention. No serious adverse events were reported. Conclusion: In patients with an initial treatment response to the Nēsos ATHENS therapy in the 12-week POC study, reductions in DAS28-CRP were sustained through 52 weeks. Although results should be interpreted cautiously given the small sample size and lack of control arm, MRI evaluation of synovitis, osteitis, bone erosion, and cartilage loss suggested no disease progression. REFERENCES: [1]Marsal, S., The Lancet Rheumatology, 2021. 3 (4): p. e262-e269. Disclosure of Interests: Charles Peterfy Consultant of: Nesos Corp, Employee of: Spire Sciences, Héctor Corominas: None declared, Juan Jose de Agustin: None declared, Carolina Perez-Garcia: None declared, Maria Lopez Lasanta: None declared, Helena Borrell Paños: None declared, D Reina-Sanz: None declared, Raimón Sanmartí: None declared, J. Narváez: None declared, Jose Antonio Narvaez: None declared, Vivek Sharma Shareholder of: Nesos Corp., Employee of: Nesos Corp., Konstantinos Alataris Shareholder of: Nesos Corp., Employee of: Nesos Corp., Mark C. Genovese Shareholder of: Nesos Corp. and Gilead, Employee of: Gilead, Matthew Baker Shareholder of: Nesos Corp., Consultant of: Nesos Corp., Sara Marsal Consultant of: Nesos, Pfizer, Sandoz, Novartis, Gilead, Grant/research support from: Nesos, BMS, Celgene, Merck Sharp and Dohme, Pfizer, Sandoz, Novartis, Sanofi, Janssen, Union Chimique Belge Pharma Citation: , volume 81, supplement 1, year 2022, page 1327Session: Rheumatoid arthritis - non biologic treatment and small molecules (Publication Only)