Novi Giovanni, Bovis Francesca, Sciolla Chiara, Frau Jessica, Minetti Matteo, Napoli Francesca, Vianello Marika, Greco Giacomo, Sechi Elia, Bellomo Andrea, Garelli Paola, Spiezia Antonio Luca, Fantozzi Roberta, Schirò Giuseppe, Ghezzi Laura, Zecca Chiara, Signoriello Elisabetta, Brambilla Laura, Lucchini Matteo, Bonavita Simona, Schiavetti Irene, Malentacchi Maria, Cocco Eleonora, Franceschini Alessandro, Mataluni Giorgia, Gastaldi Matteo, Rolando Anna, Solla Paolo, Cellerino Maria, Abbadessa Gianmarco, Lanzillo Roberta, Di Sapio Alessia, Uccelli Antonio, Sormani Maria Pia
IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
Department of Health Sciences, University of Genoa, Genoa, Italy.
CNS Drugs. 2025 May 29. doi: 10.1007/s40263-025-01191-7.
Neuromyelitis optica spectrum disorder (NMOSD) is a severely disabling autoimmune disease that predominantly impacts the optic nerves and spinal cord. It is often linked to immunoglobulin G (IgG) antibodies targeting the aquaporin-4 water channel (AQP4-IgG). Rituximab, which depletes CD20-positive B cells, is effective in reducing the frequency of NMOSD relapses. The objective of this retrospective, 5-year observational study was to evaluate the effectiveness and safety of rituximab in patients with AQP4-IgG-positive NMOSD.
We conducted a multicenter, retrospective study using prospectively collected data from 23 multiple sclerosis (MS) and NMOSD centers (22 in Italy, 1 in Switzerland). The study cohort included patients with AQP4-IgG-positive NMOSD who had completed rituximab induction therapy, with data collected up to May 2024. Two maintenance strategies were used-fixed 6-monthly infusions or reinfusions guided by flow cytometry-on the basis of CD19 or CD27 memory B-cell repopulation thresholds. Clinical outcomes included annualized relapse rate (ARR), time to first relapse (TTFR), and Expanded Disability Status Scale (EDSS) worsening, which was assessed both overall and between relapses to indirectly evaluate the possibility of inter-attack disability progression. Safety outcomes encompassed infusion-related reactions and adverse events.
A total of 138 patients were analyzed. ARR significantly decreased from 1.54 (95% confidence interval (CI) 1.34-1.75) before rituximab to 0.15 (95% CI 0.12-0.19) over the 5-year follow-up. Approximately 33% of patients experienced at least one relapse during treatment, after a median time of 5.21 months. Higher pre-rituximab relapse rates were associated with shorter TTFR. Subtle increases of 0.5-1 points in EDSS between relapses were observed in one third of patients. Mild infections were common, and 21% of patients experienced infusion-related reactions. In addition, six patients developed malignancies.
Over 5 years, rituximab consistently reduced the incidence of relapses in patients with NMOSD, though 33% of them still experienced a relapse during this period, generally within the first 6 months of treatment. No unexpected adverse events were identified. While safety monitoring remains crucial, further studies are needed to better understand rituximab's impact on NMOSD management.
视神经脊髓炎谱系障碍（NMOSD）是一种严重致残的自身免疫性疾病，主要影响视神经和脊髓。它通常与靶向水通道蛋白4水通道（AQP4-IgG）的免疫球蛋白G（IgG）抗体有关。利妥昔单抗可消耗CD20阳性B细胞，能有效降低NMOSD复发频率。这项回顾性5年观察性研究的目的是评估利妥昔单抗在AQP4-IgG阳性NMOSD患者中的有效性和安全性。
我们进行了一项多中心回顾性研究，使用了来自23个多发性硬化症（MS）和NMOSD中心（意大利22个，瑞士1个）前瞻性收集的数据。研究队列包括完成利妥昔单抗诱导治疗的AQP4-IgG阳性NMOSD患者，数据收集截至2024年5月。根据CD19或CD27记忆B细胞再填充阈值，采用两种维持策略——固定每6个月输注一次或流式细胞术指导下的再输注。临床结局包括年化复发率（ARR）、首次复发时间（TTFR）和扩展残疾状态量表（EDSS）恶化情况，对整体和复发间的情况均进行评估，以间接评估发作间期残疾进展的可能性。安全性结局包括输注相关反应和不良事件。
共分析了138例患者。在5年随访期间，ARR从利妥昔单抗治疗前的1.54（95%置信区间（CI）1.34 - 1.75）显著降至0.15（95%CI 0.12 - 0.19）。约33%的患者在治疗期间经历了至少一次复发，中位时间为5.21个月。利妥昔单抗治疗前较高的复发率与较短的TTFR相关。三分之一的患者在复发间EDSS有0.5 - 至1分的细微增加。轻度感染很常见，21%的患者出现输注相关反应。此外，6例患者发生了恶性肿瘤。
在5年期间，利妥昔单抗持续降低了NMOSD患者的复发率，尽管其中33%的患者在此期间仍有复发，通常在治疗的前6个月内。未发现意外不良事件。虽然安全监测仍然至关重要，但需要进一步研究以更好地了解利妥昔单抗对NMOSD治疗的影响。
