Ravulizumab in neuromyelitis optica spectrum disorder: first clinical experience in Chile.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a neuroimmunological astrocytopathy mediated by anti-aquaporin-4 (AQP4-IgG) antibodies that trigger complement-dependent cytotoxicity and activation of the terminal complement cascade in the central nervous system. Ravulizumab, a long-acting terminal complement C5 inhibitor, received regulatory approval in Chile in January 2025; the seven patients reported here represent the entire nationally treated cohort to date. Objectives: To describe the first clinical experience with ravulizumab in NMOSD at three Chilean centers (Clínica Alemana de Santiago, a private center, Clínica Dávila, a private center, and Hospital Clínico Universidad de Chile, a public university hospital). Methods: Retrospective, multicenter cohort study of patients with NMOSD fulfilling the 2015 International Panel for NMO Diagnosis (IPND) consensus criteria who were receiving ravulizumab. Demographic and clinical characteristics, AQP4-IgG status, baseline and follow-up Expanded Disability Status Scale (EDSS) scores, treatment indication, relapses and adverse events were analyzed through medical chart review. Results: Seven patients (100% female) were included, with a mean age at disease onset of 51.0 years (range 38-69). AQP4-IgG was positive in all patients (100%), confirmed by cell-based assay. The most common presentation over the disease course was longitudinally extensive transverse myelitis (LETM; 7/7); four patients (57.1%) also developed optic neuritis. Median baseline EDSS was 6.0. Five patients had previously failed rituximab, one discontinued rituximab because of active cancer, and one was treatment naïve. Over a median follow-up of 15 months (range 4-24) on ravulizumab, no clinical relapses were observed (0/7 patients), compared with approximately 4.5 relapses expected across the cohort's person-time had the pre-treatment relapse rate continued unchanged (observed-vs-expected analysis; see Results). EDSS declined from a baseline median of 6.0 to 2.5 (median within-patient change 1.5 points, IQR 1.0-4.0); because baseline EDSS in several patients was recorded during or shortly after an acute attack, this decrease likely reflects post-attack recovery in addition to any disability-modifying effect, and three patients remained at EDSS ≥5. Headache was the only adverse event (7/7), mild to moderate and self-limited. Conclusions: In this real-world Chilean cohort, ravulizumab was associated with complete relapse suppression over a median follow-up of 15 months and was well tolerated. These preliminary, uncontrolled observations are consistent with the relapse-prevention efficacy reported in pivotal trials and with regional consensus guidance on its use after rituximab failure, and they underscore the need to expand equitable access to complement-targeted therapies within the Chilean healthcare system.