Long-Term Effectiveness and Safety of Rituximab in Neuromyelitis Optica Spectrum Disorder: A 5-Year Observational Study.

IF 7.4 2区 医学 Q1 CLINICAL NEUROLOGY
CNS drugs Pub Date : 2025-07-01 Epub Date: 2025-05-29 DOI:10.1007/s40263-025-01191-7
Giovanni Novi, Francesca Bovis, Chiara Sciolla, Jessica Frau, Matteo Minetti, Francesca Napoli, Marika Vianello, Giacomo Greco, Elia Sechi, Andrea Bellomo, Paola Garelli, Antonio Luca Spiezia, Roberta Fantozzi, Giuseppe Schirò, Laura Ghezzi, Chiara Zecca, Elisabetta Signoriello, Laura Brambilla, Matteo Lucchini, Simona Bonavita, Irene Schiavetti, Maria Malentacchi, Eleonora Cocco, Alessandro Franceschini, Giorgia Mataluni, Matteo Gastaldi, Anna Rolando, Paolo Solla, Maria Cellerino, Gianmarco Abbadessa, Roberta Lanzillo, Alessia Di Sapio, Antonio Uccelli, Maria Pia Sormani
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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

利妥昔单抗治疗视神经脊髓炎的长期有效性和安全性:一项为期5年的观察研究。
背景:视神经脊髓炎谱系障碍(NMOSD)是一种严重致残性自身免疫性疾病,主要影响视神经和脊髓。它通常与靶向水通道蛋白-4 (AQP4-IgG)的免疫球蛋白G (IgG)抗体相连。利妥昔单抗可消耗cd20阳性B细胞,可有效降低NMOSD复发的频率。这项为期5年的回顾性观察性研究的目的是评估利妥昔单抗治疗aqp4 - igg阳性NMOSD患者的有效性和安全性。方法:我们进行了一项多中心回顾性研究,前瞻性地收集了23个多发性硬化症(MS)和NMOSD中心的数据(22个在意大利,1个在瑞士)。该研究队列包括已完成利妥昔单抗诱导治疗的aqp4 - igg阳性NMOSD患者,数据收集至2024年5月。基于CD19+或CD27+记忆b细胞再生阈值,采用两种维持策略-固定6个月输注或在流式细胞术指导下再输注。临床结果包括年复发率(ARR)、首次复发时间(TTFR)和扩展残疾状态量表(EDSS)恶化,该量表在总体和两次复发之间进行评估,以间接评估两次发作间残疾进展的可能性。安全性指标包括输注相关反应和不良事件。结果:共分析138例患者。5年随访期间,ARR从利妥昔单抗治疗前的1.54(95%可信区间(CI) 1.34-1.75)显著下降至0.15 (95% CI 0.12-0.19)。大约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。较高的利妥昔单抗前复发率与较短的TTFR相关。在三分之一的患者中,EDSS在两次复发之间有0.5-1点的轻微升高。轻度感染很常见,21%的患者出现了输液相关反应。此外,6例患者发展为恶性肿瘤。结论:在5年多的时间里,利妥昔单抗持续降低了NMOSD患者的复发发生率,尽管33%的患者在这段时间内仍然经历了复发,通常是在治疗的前6个月内。未发现意外不良事件。虽然安全性监测仍然至关重要,但需要进一步的研究来更好地了解利妥昔单抗对NMOSD管理的影响。
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来源期刊
CNS drugs
CNS drugs 医学-精神病学
CiteScore
12.00
自引率
3.30%
发文量
82
审稿时长
6-12 weeks
期刊介绍: CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes: - Overviews of contentious or emerging issues. - Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses. - Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. - Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry. - Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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