Monoclonal Antibody-Based Therapies for AQP4-Positive NMOSD

Inclusion Criteria: * Subjects must demonstrate capacity to comprehend the study's objectives and associated risks, provide written informed consent, and authorize utilization of confidential health information in compliance with national and regional data protection regulations. * Enrollment is permitted regardless of biological sex, with age ≥18 and ≤65 years (inclusive) at the time of informed consent provision. * All females of childbearing potential and biologically male participants must employ contraceptive measures meeting clinical trial standards throughout the study duration and for at least 30 days following the final administration of investigational therapy. Additionally, participants must abstain from gamete donation during the study period and for ≥30 days post-treatment cessation. * Confirmed diagnosis of aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive neuromyelitis optica spectrum disorders (NMOSD) per the 2015 International Consensus Diagnostic Criteria, with serological or cerebrospinal fluid verification of AQP4-IgG positivity for inclusion in the AQP4-NMOSD cohort. Participants must have provided documented consent for therapeutic intervention with one monoclonal antibody-based biologics. * Neurological examination demonstrating clinical stability within 30 days preceding baseline (Visit 1). Exclusion Criteria: * Medical History and Current Health Status 1. Clinically significant medical history of cardiac, endocrine, hematologic, hepatic, immune, infectious, metabolic, renal, pulmonary, neurological, dermatologic, psychiatric, or other major systemic conditions that, in the investigator's judgment, would preclude safe trial participation. 2. Prior cerebrovascular events resulting in a baseline modified Rankin Scale (mRS) score \>3. 3. Hypersensitivity to the investigational therapeutic agent(s) or their excipients. * Infection Risk 1. Documented history or positive screening test for human immunodeficiency virus (HIV). 2. Active hepatitis C virus (HCV) infection, defined as detectable HCV RNA with concomitant anti-HCV antibody positivity. Subjects with anti-HCV antibody positivity and undetectable HCV RNA remain eligible. 3. Active hepatitis B virus (HBV) infection, defined as hepatitis B surface antigen (HBsAg) positivity and/or total hepatitis B core antibody (anti-HBc) positivity. Subjects with prior natural infection (HBsAg-negative, anti-HBc-positive, and anti-HBs-positive) or vaccination-induced immunity (HBsAg-negative, anti-HBc-negative, and anti-HBs-positive) are eligible. 4. Chronic, recurrent, or severe infections (e.g., pneumonitis, sepsis) within 90 days prior to baseline (Visit 1). 5. History of active tuberculosis (TB) or latent TB infection, defined by positive interferon-gamma release assay (IGRA) results or two consecutive tuberculin skin tests. 6. Active bacterial, fungal, or viral infections (including upper respiratory tract infections) within 28 days prior to baseline. Subjects with localized fungal infections (e.g., candidiasis, dermatophytosis) may undergo re-screening post-treatment. 7. Contraindications to rescue therapies, including rituximab, intravenous immunoglobulin (IVIG), high-dose corticosteroids, or cyclophosphamide. 8. Prior exposure to total lymphoid irradiation, cladribine, T-cell or T-cell receptor vaccination, total body irradiation, or hematopoietic stem cell transplantation at any time. * Additional Exclusion Criteria 1. Clinically significant suicidal ideation or behavior within the past 12 months, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS). 2. Unwillingness or inability to comply with protocol-mandated procedures. 3. Severe auditory/visual impairment, language barriers, claustrophobia, or other conditions precluding neuropsychological assessments or MRI completion. 4. Any other condition deemed by the investigator or sponsor to compromise subject eligibility or study integrity.