A systematic review and meta-analysis of the efficacy and safety of eculizumab in AQP4-IgG-positive neuromyelitis optica spectrum disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an extremely uncommon autoimmune inflammatory condition affecting the central nervous system with clinical features including recurrent episodes of optic neuritis and transverse myelitis. Complement-dependent astrocyte damage is the predominant mechanism involved in the development of NMOSD, which is positive for anti-aquaporin-4 antibodies (AQP4). Eculizumab, an inhibitor of the complement C5 protein, shows efficacy in preventing relapses. Objective Evaluating the effectiveness and safety of eculizumab in AQP4-IgG seropositive NMOSD subjects, specifically regarding preventing relapse in addition to annualized relapse rate (ARR), neurological disability, and SAEs METHODS: The systematic review and meta-analysis were done according to PRISMA guidelines. A search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library was performed from inception until March 2026 for RCTs investigating eculizumab in AQP4-IgG-seropositive NMOSD patients. The time to first adjudicated relapse and ARR were chosen as primary outcomes, while the EDSS scores and SAEs were selected as secondary outcomes. Phase III RCTs were included in the study RESULTS: Eculizumab significantly reduced the risk of adjudicated relapse compared with placebo or conventional immunosuppressive therapy (HR = 0.07; 95% CI: 0.03-0.18; p < 0.001). It also significantly reduced ARR (RR = 0.15; 95% CI: 0.08-0.29; p < 0.001). More than 95% of patients receiving eculizumab remained relapse-free during follow-up. EDSS scores generally remained stable, suggesting preservation of neurological function. The available evidence indicated an acceptable safety profile, although the limited number of trials and relatively short follow-up periods restrict conclusions regarding long-term safety CONCLUSION: Eculizumab decreases relapse rates and ARR in AQP4-IgG-positive NMOSD patients and is considered safe. Nevertheless, the lack of RCTs, small sample sizes, heterogeneity in follow-up periods, and limited data on long-term safety and cost-effectiveness require additional studies.