Factors for Rituximab Refractoriness in AQP4-IgG+ NMOSD: A Cohort Study

Area of Science:

• Neuroimmunology
• Autoimmune CNS disorders
• Therapeutic monitoring

Background:

• Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune central nervous system (CNS) disease.
• Aquaporin-4 antibodies (AQP4-IgG) are key biomarkers in NMOSD.
• Rituximab, a CD20+ B-cell depleting therapy, is a common first-line treatment, but some patients show resistance.

Purpose of the Study:

• To investigate factors associated with treatment refractoriness in AQP4-IgG-positive NMOSD patients receiving rituximab.
• To identify predictors of therapeutic failure in this patient cohort.

Main Methods:

• Retrospective cohort study of 54 AQP4-IgG-positive NMOSD patients treated with rituximab (2006-2023).
• Analysis of clinical, imaging, and genetic data.
• Treatment failure defined as relapse after 6 months of rituximab initiation; statistical analyses included MANCOVA and Cox regression.

Main Results:

• 22.2% of patients experienced rituximab treatment failure.
• Asymptomatic lesions during follow-up were a significant predictor of treatment failure (p=0.02) and increased relapse risk (HR=25.9).
• Age, sex, baseline EDSS, and gadolinium enhancement were not significantly associated with treatment failure; FCGR3A-V158F polymorphism showed no significant relationship.

Conclusions:

• Asymptomatic lesions are a strong indicator of rituximab treatment failure in AQP4-IgG-positive NMOSD.
• Early identification of these lesions is crucial for guiding treatment decisions.
• This finding may prompt clinicians to consider alternative therapies for patients with asymptomatic lesions.