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

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.

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).

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.

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.

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.