NMOSD
Conditions
Keywords
NMOSD, Intravenous methylprednisolone, Efgartigimod, Eculizumab, Plasma exchange
Brief summary
This study aims to evaluate the efficacy and safety of different monoclonal antibody in the acute phase of neuromyelitis optica spectrum disorder (MAAP-NMO). It will also examine immune-related biomarkers and their relationship with treatment response to provide evidence for optimizing acute-phase therapeutic strategies.
Detailed description
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.
Interventions
None listed
Sponsors
First Affiliated Hospital of Chongqing Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age at onset ≥18 years, any gender. 2. 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. 3. 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. 4. Expanded Disability Status Scale (EDSS) score at enrollment ≥3 and ≤8 points. 5. Planned to receive or currently receiving intravenous methylprednisolone (IVMP) treatment, and not on or only using conventional immunosuppressive maintenance therapy. 6. Able to comply with standardized follow-up, with an expected minimum follow-up of 12 months during the study period. 7. Signed informed consent by the patient or legal guardian (if applicable).
Exclusion criteria
1. Participation in a randomized clinical trial with blinded treatment allocation. 2. Received treatment with monoclonal antibody (including rituximab, satralizumab, inebilizumab, eculizumab, efgartigimod, etc.) within 3 months prior to screening. 3. Received treatment with IVIg, plasma exchange (PE), IVMP, or oral corticosteroids \>30 mg/day within 1 month prior to screening. 4. Incomplete or unavailable follow-up data, expected inability to complete follow-up, or poor compliance. 5. Patients who have independently discontinued immunotherapy or demonstrate poor adherence. 6. 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. 7. Pregnant or breastfeeding women, or women planning pregnancy in the near future (contraception required during treatment). 8. Any other condition deemed by the investigators to make participation in the study inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Expanded Disability Status Scale (EDSS) score | 1 months | Change in Expanded Disability Status Scale (EDSS) score from baseline to 1 months after treatment (EDSS: Minimum Score 1, Maximum score 10, higher scores mean a worse outcome). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in serum AQP4-IgG titer | 1, 3 and 6 months | Change in serum AQP4-IgG titer before treatment and at 1, 3, and 6 months after immunotherapy, measured by cell-based assay. |
| Change in serum GFAP level | 1, 3, and 6 months | Change in serum GFAP level before treatment and at 1, 3, and 6 months after immunotherapy, measured by Simoa immunoassay. |
| Change in Expanded Disability Status Scale (EDSS) score | 3 and 6 months | Change in Expanded Disability Status Scale (EDSS) score from baseline at 3 and 6 months (EDSS: Minimum Score 1, Maximum score 10, higher scores mean a worse outcome). |
| Percentage of Participants with Improvement | 1, 3 and 6 months | Improvement is defined as: 1. ≥1.0-point decrease from baseline if baseline EDSS ≤5.5; 2. ≥0.5-point decrease from baseline if baseline EDSS \>5.5. |
| Change in Low-Contrast Visual Acuity (LCVA) | 1, 3 and 6 months | Low-Contrast Visual Acuity (LCVA), using a standardized low-contrast ETDRS visual acuity chart, the number of letters that the patient can identify at a sitting position and a distance of 4 meters / 1 meter is measured to reflect the recovery of visual function. |
| Percentage of Participants without relapse | 1, 3 and 6 months | Relapse is defined as new neurological symptoms or significant worsening of existing symptoms lasting ≥24 hours during the follow-up period, excluding causes such as infection or fever, and confirmed by imaging or clinical evaluation. |
| Change in serum NfL level | 1, 3, and 6 months | Change in serum NfL level before treatment and at 1, 3, and 6 months after immunotherapy, measured by Simoa immunoassay. |
| Changes in serum IL-6, IL-17, TNF-α, IFN-γ, and IL-10 levels | 1, 3 and 6 months | Changes in serum IL-6, IL-17, TNF-α, IFN-γ, and IL-10 levels before treatment and at 1, 3, and 6 months after immunotherapy, measured by multiplex bead-based immunoassay. Units: pg/mL. |
| Changes in T/B cell subsets | 1, 3 and 6 months | Changes in T/B cell subsets (immune function monitoring) before treatment and at 1, 3, and 6 months after immunotherapy. |
| Changes in serum lactate, pyruvate, and glucose levels | 1, 3 and 6 months | Energy metabolism will be assessed by quantifying serum lactate, pyruvate, and glucose concentrations at baseline, 1, 3, and 6 months using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Units: mmol/L. |
| Changes in serum lipid metabolites | 1, 3 and 6 months | Lipid metabolism will be evaluated by measuring serum cholesterol at baseline, 1, 3 and 6 months using LC-MS/MS. Units: µmol/L. |
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | 1, 3 and 6 months | AEs are any unfavorable medical occurrences during the study period, regardless of causality. SAEs include events resulting in death, life-threatening conditions, permanent or significant disability or loss of function, hospitalization or prolongation of hospitalization, congenital anomaly, or birth defect. Record the time of onset, type, severity, and outcome. Drug-related adverse effects of biologics (e.g., efgartigimod, inebilizumab) will be specifically monitored, including hypogammaglobulinemia (assessed at baseline, 1, 3, and 6 months) and occurrence of meningococcal infection. |
| MRI changes after immunotherapy | 1 and 6 months | MRI changes including improvement of acute-phase pre-existing T2 hyperintense lesions and enhancing lesions (volume reduction, signal attenuation, or decreased enhancement), and the number of new and/or enlarged T2 hyperintense lesions or new enhancing lesions. |
Contacts
Primary ContactJinzhou Feng, Ph.D
Outcome results
None listed