Abstract
Background: Neuromyelitis optica spectrum disorder aquaporin-4 positive (NMOSD AQP4-IgG) is a severe autoimmune disease where acute attacks, driven by complement-mediated astrocyte destruction, cause profound disability. The pathological cascade culminates in the formation of the C5b-9 membrane attack complex (MAC), leading to astrocytolysis and irreversible damage. Standard acute treatments, such as corticosteroids and plasma exchange, are often insufficient for severe attacks, highlighting an unmet need for therapies that can rapidly halt tissue injury.
Materials and methods: A narrative review is carried out using Embase, PubMed and The Cochrane Library, whose search covers neuromyelitis optica spectrum disorder (NMOSD), aquaporin 4 positive (AQP-4), complement C5 inhibitors, ravulizumab, eculizumab including articles published from inception to July 2025.
Rationale and evidence: Complement C5 inhibitors, including eculizumab and ravulizumab, have transformed relapse prevention in NMOSD and possess a compelling pathophysiological rationale for use as an acute rescue therapy. By binding complement component C5, these agents act as a "circuit breaker," immediately blocking the final common pathway of tissue destruction. This mechanism is distinct and complementary to standard care. The pharmacology of these agents is ideal for emergency intervention, achieving complete terminal complement blockade within an hour of administration. While randomized controlled trials are lacking, a growing body of case reports and small series consistently demonstrates that initiating C5 inhibition in severe, refractory attacks is associated with rapid cessation of neurological deterioration, often within 24-48 hours, and subsequent clinical improvement.
Conclusion: C5 inhibition is a powerful, mechanistically-targeted adjunctive therapy for severe, refractory AQP4-IgG NMOSD attacks. Supported by a strong pathophysiological rationale, rapid pharmacodynamic action, and consistent positive signals from emerging clinical evidence, acute C5 blockade represents a vital strategy to preserve neurological function by directly arresting ongoing immune-mediated tissue injury. Further systematic investigation is warranted to formalize its role in the acute treatment algorithm.
Keywords
Aquaporin-4, Neuromyelitis optica spectrum disorder (NMOSD), Eculizumab, Ravulizumab