Ab1036 Vagus Nerve Stimulation as a Novel Treatment of Fatigue in Patients With Systemic Lupus Erythematosus: A Randomized, Double-Blinded, Sham-Controlled, Clinical Trial

Background: Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that carries an increased risk of comorbidity, organ damage, low quality of life, work incapacity, and mortality. The cornerstone of current care is immunosuppression aimed to reduce disease activity, which, however, has limited effect in relieving patients from constitutive symptoms like fatigue. To reduce the use of traditional immunosuppressing treatment, alternative means of attenuating autoimmune inflammation and treatment-resistant symptoms, such as fatigue, are in demand. Recent research indicates that electrical stimulation of the autonomic parasympathetic vagus nerve holds this potential by modulating the vagally-mediated cholinergic anti-inflammatory reflex. Objectives: Our purpose was to modulate the autonomic nervous system function by transcutaneous non-invasive vagus nerve stimulation (tVNS) with a handheld, self-administered, class IIa medical device and assess patients' responses to perceived levels of fatigue. We hypothesized that adjuvant treatment with tVNS in addition to standard care would improve patient-reported fatigue in SLE patients. Methods: Sixty-four SLE patients with signs of fatigue (FACIT-F score <40) and autonomic dysfunction (Composite Autonomic Symptoms Score >12) were randomized 1:1 to active or sham tVNS in this double-blinded parallel-group study (Zinglersen et al., 2022). Patients reported fatigue weekly by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale, a validated 13-item questionnaire of patient-perceived fatigue on daily activities and function over the past week. In period 1 (1 week), patients received 4 minutes of tVNS 4 times daily. After a 2-week pause, period 2 (8 weeks) entailed 4 minutes of tVNS 2 times daily. Statistical analysis was performed as general linear modeling of repeated measures in IBM SPSS Statistics. Results: In fifty-eight SLE patients included for analysis (n=29 patients in each group), mean FACIT-F scores did not differ between active and sham tVNS at baseline nor after the 2-week pause. However, active tVNS compared to sham displayed a significantly higher mean FACIT-F score (i.e., less fatigued) after 1 week of stimulation, for both intervention periods. This effect persisted during the remaining 7 weeks of period 2 (Figure 1, p<0.04). Conclusion: In SLE patients with signs of fatigue and autonomic dysfunction, treatment with active tVNS in addition to standard care improved patient-perceived levels of fatigue in daily activities and function. The effects of tVNS on secondary outcomes such as autonomic symptoms and function, SLE disease activity, health-related quality of life, immunologic biomarkers, and organ function endpoints remain to be analyzed. However, reaching the primary endpoint in this study holds promise for tVNS to constitute a paradigmatic shift in the care of patients with chronic inflammatory diseases like SLE. REFERENCES: [1] Zinglersen, A. H., Drange, I. L., Myhr, K. A., Fuchs, A., Pfeiffer-Jensen, M., Brock, C., & Jacobsen, S. (2022). Vagus nerve stimulation as a novel treatment for systemic lupus erythematous: study protocol for a randomised, parallel-group, sham-controlled investigator-initiated clinical trial, the SLE-VNS study. BMJ open, 12(9), e064552. https://doi.org/10.1136/bmjopen-2022-064552 Acknowledgements: The Danish Rheumatism Association. Disclosure of Interests: None declared.