AQP4-IgG Dynamics and Exploratory Assessment of SERA-3 in Neuromyelitis Optica Spectrum Disorder Treated with Satralizumab

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune condition driven by aquaporin-4 immunoglobulin G (AQP4-IgG). The current treatment paradigm focuses on mitigating clinical relapses and disability accumulation, leaving the underlying serological activity unaddressed. This study evaluated the capacity of satralizumab to achieve a comprehensive remission, as defined by the Serological, Relapse, and Accumulated-disability Remission (SERA-3) target. METHODS: In this multicenter, real-world cohort study, patients with NMOSD from three tertiary centers in China initiating satralizumab were enrolled. AQP4-IgG levels were measured at baseline, 6, and 12 months. Clinical efficacy [annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS)] and safety were evaluated. Heterogeneity in antibody response was analyzed, and baseline characteristics potentially associated with titer reduction were explored. RESULTS: Of the 19 patients who were AQP4-IgG seropositive at baseline, 7 (36.84%) met the strict definition of SERA-3 Complete. Of these, 4 patients achieved seroconversion at month 6 and remained seronegative through month 12, whereas 3 first achieved seroconversion at month 12. An additional 5 (26.32%) showed a reduction in AQP4-IgG titers. Satralizumab treatment was associated with marked clinical benefit. Among 33 patients included in the clinical efficacy analysis, 27 (81.82%) remained relapse-free during follow-up, median ARR decreased from 0.92 (IQR 0.56-1.59) to 0 (IQR 0-0), and EDSS scores remained stable in most patients. Exploratory analyses suggested that patients achieving serological response were older at disease onset (57.42 ± 17.82 versus 42 ± 14.24 years, p = 0.039) and had experienced fewer pre-treatment relapses (median 2 versus 5, p = 0.049). Satralizumab was generally well tolerated, including in older patients. CONCLUSIONS: Our findings support SERA-3 as a potential treatment framework for NMOSD. Satralizumab was associated with attainment of serological, relapse, and disability remission in a substantial proportion of patients, supporting further prospective evaluation of SERA-3 as a hypothesis-generating outcome framework.