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

OBJECTIVE

Neuromyelitis optica spectrum disorder (NMOSD) is a severe autoimmune condition of the central nervous system (CNS), often associated with aquaporin-4 antibodies (AQP4-IgG). Rituximab, a CD20+ B-cell depleting monoclonal antibody, is widely used as first-line therapy. However, a subset of patients exhibits treatment refractoriness. Our objective is to investigate factors associated with treatment refractoriness in AQP4-IgG-positive NMOSD patients treated with rituximab.

METHODS

This retrospective cohort study included 54 AQP4-IgG-positive NMOSD patients treated with rituximab between 2006 and 2023. Clinical, imaging, and genetic data were analyzed. Treatment failure was defined as at least one relapse occurring after 6 months of rituximab initiation. Statistical analyses included multivariate analyses of covariance (MANCOVA) and Cox regression to identify independent predictors of treatment failure.

RESULTS

Among the 54 patients (82.5% female, median age 45 years, range: 34-54.5), 12 (22.2%) exhibited rituximab treatment failure. The presence of asymptomatic lesions during follow-up was significantly associated with treatment failure (p = 0.02) and emerged as an independent predictor in MANCOVA (Wilks' Lambda = 0.01, F = 20.5, η2 = 0.357, p < 0.001). These lesions also increased the risk of clinical relapses (HR = 25.9, 95% CI = 3.09-218, p < 0.01). Other variables, including age, sex, baseline EDSS, and persistent gadolinium enhancement, were not significantly associated with treatment failure. Genetic analysis of the FCGR3A-V158F polymorphism did not reveal a significant relationship with treatment outcomes.

INTERPRETATION: Asymptomatic lesions during rituximab treatment are a strong predictor of therapeutic failure in AQP4-IgG-positive NMOSD patients. Early identification of these lesions could guide clinicians in optimizing treatment strategies, including transitioning to alternative therapies.