Efficacy and Safety of Monoclonal Antibody in Acute Phase of Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system characterized primarily by humoral immune dysfunction. The acute phase is highly disabling; therefore, improving the effectiveness of acute-phase interventions represents a critical challenge in the clinical management of NMOSD. Conventional acute treatments such as intravenous methylprednisolone (IVMP), plasma exchange (PE), and intravenous immunoglobulin (IVIg) provide only limited rates of remission. The advent of novel biologics has expanded therapeutic options for NMOSD, but consensus regarding the optimal treatment approach during the acute phase has not yet been established.

This project is a multicenter, prospective, real-world observational study. A total of 35-45 patients with acute-phase NMOSD from 12 centers across China will be enrolled and followed systematically for at least 6 months according to a standardized protocol. The study will evaluate the real-world efficacy and safety of different monoclonal antibodies, primarily focusing on efgartigimod and eculizumab, in the treatment of acute-phase NMOSD. It will further assess their impact on symptom and neurological disability improvement, as well as their effects on immunological parameters, biomarkers, and imaging outcomes, in order to explore the optimal acute-phase immunotherapy strategy in NMOSD.

Inclusion criteria

• Age at onset ≥18 years, any gender.
• Patients meeting the 2015 International Panel for NMO Diagnosis (IPND) criteria for NMOSD and currently in the acute phase, defined as new or significantly worsened neurological deficits lasting >24 hours, with onset within <14 days, excluding pseudo-relapses caused by fever, infection, or metabolic disturbances. The acute relapse must meet at least one of the following clinical phenotypes: a) Optic neuritis (ON): EDSS visual function score ≥3; b) Transverse myelitis (TM): EDSS pyramidal function score ≥2. NMOSD-related syndromes (e.g., area postrema syndrome, acute brainstem syndrome, acute diencephalic syndrome, cerebral syndrome) may be present as concomitant features but cannot be the sole or primary manifestation.
• Serum AQP4-IgG positive by cell-based assay (CBA) with a titer ≥1:32, and negative for MOG-IgG (CBA or LCBA) and GFAP-IgG.
• Expanded Disability Status Scale (EDSS) score at enrollment ≥3 and ≤8 points.
• Planned to receive or currently receiving intravenous methylprednisolone (IVMP) treatment, and not on or only using conventional immunosuppressive maintenance therapy.
• Able to comply with standardized follow-up, with an expected minimum follow-up of 12 months during the study period.
• Signed informed consent by the patient or legal guardian (if applicable).

Exclusion criteria

• Participation in a randomized clinical trial with blinded treatment allocation.
• Received treatment with monoclonal antibody (including rituximab, satralizumab, inebilizumab, eculizumab, efgartigimod, etc.) within 3 months prior to screening.
• Received treatment with IVIg, plasma exchange (PE), IVMP, or oral corticosteroids >30 mg/day within 1 month prior to screening.
• Incomplete or unavailable follow-up data, expected inability to complete follow-up, or poor compliance.
• Patients who have independently discontinued immunotherapy or demonstrate poor adherence.
• Presence of severe underlying diseases or other conditions that may affect the safety of immunotherapy or the interpretation of study results, including but not limited to: a) Chronic or active infections requiring long-term systemic treatment (e.g., progressive multifocal leukoencephalopathy, chronic renal infection, chronic respiratory infection with bronchiectasis, active tuberculosis, active hepatitis C, etc.); b) Positive hepatitis B serology (except in individuals with prior vaccination); c) History or suspicion of tuberculosis; d) Positive HIV serology; e) History or current clinically significant adverse reactions (including severe allergic reactions) related to corticosteroids, FcRn antagonists, or complement inhibitors.
• Pregnant or breastfeeding women, or women planning pregnancy in the near future (contraception required during treatment).
• Any other condition deemed by the investigators to make participation in the study inappropriate.