2026 American Academy of Neurology Autoimmune Abstract Website

Objective:

N/A

Background:

Aquaporin-4 (AQP4) positive NMOSD is a severe autoimmune demyelinating disease often managed with C5 complement inhibitors like Ravulizumab. This report details the first reported case of a patient experiencing a breakthrough exacerbation while adherent to Ravulizumab, highlighting the utility of complement monitoring and therapeutic challenges.

Design/Methods:

A 30-year-old male, diagnosed with AQP4-positive NMOSD 1.5 years previously after a longitudinally extensive transverse myelitis found to have 1:1000 titer of AQP-4 antibody. He was adherent to Ravulizumab since that time with the longest variation from the ideal infusion date being 5 days. He then presented for 1 month of right vision loss. Exam found finger counting visual acuity OD with color vision loss and a large central scatoma. MRI revealed subtle enhancement in the right optic nerve. Free C5 levels are not commercially available, so Functional C5 Total C5 and C5a were tested. Functional C5 was reduced but not completely eliminated (13.8 normal range > 23), and C5a was normal, possibly indicating some successful breakdown of C5 into C5a and C5b consistent with incomplete complement inhibition. There was a significant amount of weight gained during observation period.

Acute treatment involved high-dose intravenous corticosteroids for 5 days followed by plasmapheresis for 5 days, leading to only partial visual improvement (20/200 OD). Given the objective evidence of incomplete complement inhibition and the breakthrough disease, the patient opted to transition from Ravulizumab to Eculizumab for long-term management. Further C5a level monitoring is planned to guide ongoing therapy.

Results:

N/A

Conclusions:

This case, to the best of our knowledge, reports the first NMOSD relapse on Ravulizumab. We believe this was due to incomplete complement inhibition in the setting of significant amount of weight gain. It emphasizes the critical importance of objective complement activity monitoring to identify suboptimal blockade and guide crucial therapeutic decisions in patients with refractory NMOSD.