Long‐Term Efficacy of Immunotherapy in Autoimmune Autonomic Ganglionopathy—A 10‐Year Follow Up Study

Objective Autoimmune autonomic ganglionopathy (AAG) is a rare but potentially treatable cause of severe autonomic failure. Evidence guiding long‐term immunotherapy, treatment sequencing, and residual autonomic impairment is limited. We evaluated long‐term treatment response, residual autonomic dysfunction, and relapse patterns in patients with seropositive AAG. Methods Patients with seropositive AAG undergoing longitudinal follow‐up with repeated quantitative autonomic assessments before and after immunotherapy were included. Residual autonomic impairment was assessed using cardiovascular, pupillary, and urinary autonomic biomarkers, need for anti‐hypotensive medications or catheterisation, and patient‐reported symptoms measured by the COMPASS‐31 questionnaire. Results Of 18 patients with seropositive AAG, 16 had longitudinal quantitative autonomic testing, antibody titres, COMPASS‐31 scores, and documented medication and catheter use before and after immunotherapy. At baseline, all 16 had widespread autonomic failure. All received plasma exchange, 10 received intravenous immunoglobulins, and 11 were treated with oral prednisolone followed by steroid‐sparing agents. Treatment was associated with significant improvements in cardiovascular autonomic markers, antibody titres, and pupillary light responses, with non‐significant improvements in COMPASS‐31 scores. Four patients discontinued catheterisation. Two patients were refractory to plasma exchange and intravenous immunoglobulins but responded to prednisolone. Two patients relapsed while receiving steroid‐sparing immunotherapy. High antibody titres correlated with the severity of cardiovascular and urinary dysfunction at disease onset, but not during follow‐up. Interpretation Prolonged stepwise immunosuppression in seropositive AAG is associated with sustained objective autonomic improvement, although residual impairment and relapse remain common. These findings support individualised, biomarker‐guided immunotherapy and highlight the need for ongoing supportive management of autonomic complications.