Long-term treatment outcomes of immunotherapy in autoimmune autonomic ganglionopathy

<h3>Background</h3> The efficacy of long-term treatment in patients with AAG is still unknown. We evaluated the response to immunotherapy, and the degree of residual autonomic impairment in our cohort. <h3>Methods</h3> We longitudinally characterised patient response to immunotherapy with a multimodal autonomic biomarker assessment before and after treatment. All results are shown as average ± SD. <h3>Results</h3> 23 patients (53±13 years old) were followed for 5±3 years. 3 patients with paraneoplastic AAG died during follow-up. Before immunotherapy, 18 patients were on anti- hypotensive medications, 11 needed catheterisation and 18 laxatives. ΔSBP during HUT was - 68±29 mmHg, time tolerated on HUT was 5±4 minutes and the orthostatic intolerance ratio (OIR, ΔSBP/time on HUT) was 14. RSA was reduced (6±5 bpm), and absent in 11 subjects. 18 patients had positive anti-gAChR antibodies. 10 patients received PLEX only, 1 IVIg only, and 12 a combination of both. 13 patients received steroids, 11 needed further immunosuppression. At last follow-up, 18 patients were on anti-hypotensive medications, 4 patients still needed catheterisation and 11 laxatives. The severity of OH improved (ΔSBP = - 53±40 mmHg, time on tilt = 9±4 minutes, OIR = 6). RSA improved in 10 patients (8±9 bpm). 4 patients with initially severe autonomic failure and high anti-gAChR antibodies titre seroconverted. <h3>Conclusion</h3> A stepwise, prolonged immunosuppression improves the severity of autonomic failure in AAG over time. A degree of residual impairment remains in more refractory patients.