Marrodan Mariano, Piedrabuena María A, Zarate María A, Rodríguez Murúa Sofía, Surace Ezequiel I, Farez Mauricio F, Fiol Marcela P, Ysrraelit María C, Correale Jorge
Departamento de Neurología, Fleni, Buenos Aires, Argentina.
Centro de Investigación en Enfermedades Neuroinmunológicas (CIEN), Fleni, Buenos Aires, Argentina.
Ann Clin Transl Neurol. 2025 Aug;12(8):1566-1574. doi: 10.1002/acn3.70095. Epub 2025 Jun 10.
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.
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.
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, η = 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.
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.
视神经脊髓炎谱系障碍（NMOSD）是一种严重的中枢神经系统（CNS）自身免疫性疾病，常与水通道蛋白4抗体（AQP4-IgG）相关。利妥昔单抗是一种可清除CD20+B细胞的单克隆抗体，被广泛用作一线治疗药物。然而，有一部分患者对治疗无反应。我们的目的是研究接受利妥昔单抗治疗的AQP4-IgG阳性NMOSD患者中与治疗无反应相关的因素。
这项回顾性队列研究纳入了2006年至2023年间接受利妥昔单抗治疗的54例AQP4-IgG阳性NMOSD患者。对临床、影像学和基因数据进行了分析。治疗失败定义为利妥昔单抗开始使用6个月后至少发生一次复发。统计分析包括多变量协方差分析（MANCOVA）和Cox回归，以确定治疗失败的独立预测因素。
在这54例患者中（女性占82.5%，中位年龄45岁，范围：34 - 54.5岁），12例（22.2%）出现利妥昔单抗治疗失败。随访期间无症状病变的存在与治疗失败显著相关（p = 0.02），并在MANCOVA中成为独立预测因素（威尔克斯Lambda = 0.01，F = 20.5，η = 0.357，p < 0.001）。这些病变也增加了临床复发的风险（HR = 25.9，95%CI = 3.09 - 218，p < 0.01）。其他变量，包括年龄、性别、基线扩展残疾状态量表（EDSS）和钆持续强化，与治疗失败无显著相关性。FCGR3A-V158F多态性的基因分析未发现与治疗结果有显著关系。
利妥昔单抗治疗期间的无症状病变是AQP4-IgG阳性NMOSD患者治疗失败的有力预测指标。早期识别这些病变可为临床医生优化治疗策略提供指导，包括转向替代疗法。
