Complement Inhibition for Acute Neuromyelitis Optica Spectrum Disorder Attacks: Insights From an International Case Series.

BACKGROUND AND

objectivesNeuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune disease mainly driven by aquaporin-4 antibodies (AQP4-IgG). During an attack, AQP4-IgG activates the complement system, leading to astrocyte destruction, inflammation, neuronal damage, and thus devastating and often irreversible neurologic deficits. Terminal complement inhibitors such as eculizumab and ravulizumab effectively prevent relapses, yet their therapeutic potential in stopping ongoing complement-mediated injury during acute attacks remains insufficiently explored.

methodsWe conducted a multinational retrospective case series across NMOSD-specialized centers in 6 countries, analyzing 33 AQP4-IgG-positive patients (mean age: 48.1 years; 28 women) treated with component 5 (C5) inhibition during or shortly after acute relapse (mean 20.1 days from symptom onset; range 2-62). Eculizumab was used in 25 patients and ravulizumab in 8. Two additional patients were excluded because of delayed treatment initiation beyond 62 days.

resultsLesion locations included myelitis (57.6%) and optic neuritis (30.3%). Expanded Disability Status Scale scores worsened from a pre-relapse median of 0 (interquartile range [IQR] 0-2) to a nadir of 6.5 (IQR 3.5-8), improving to 3.5 (IQR 3-6.5) at 1-3 months and 2.5 (IQR 2-6) at 6 months. All patients stabilized clinically; 20 continued C5 inhibition as attack-preventing therapy. Good, moderate, and poor/absent recovery were observed in 15, 11, and 7 patients, respectively. Earlier treatment was associated with better outcomes: treatment within 21 days yielded an odds ratio of 1.58 (95% CI 0.32-8.52) for good response. Plasma exchange was administered in 57.6% and was associated with higher overall response rates, but not with good response alone. DISCUSSION: These findings highlight the potential of complement inhibition as a treatment option for acute NMOSD attacks, particularly in patients with insufficient response to standard therapies. Given the absence of clinical worsening and the encouraging course observed in most of the patients, further investigation into the role of C5 inhibition in acute attack management is warranted. CLASSIFICATION OF EVIDENCE: This retrospective case series provides Class IV evidence that the C5 complement inhibitors eculizumab or ravulizumab may improve disability in patients with NMOSD when given during or shortly after acute relapse.