AURICULAR TRANSCUTANEOUS HI-FREQUENCY E-MMUNOTHERAPY SEQUENCES (ATHENS) for the TREATMENT of RHEUMATOID ARTHRITIS: 1-YEAR CHANGES in SYNOVITIS, OSTEITIS, and BONE EROSION

ABSTRACT

Background: Current pharmacological treatments remain inadequate for a signifcant proportion of patients with rheumatoid arthritis (RA), and thus alternative treatment approaches are needed. Prior results from the frst 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-RAM-RIS 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). 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.