Buttari Fabio, Dolcetti Ettore, Rizzo Francesca Romana, Rizzi Caterina, Lauritano Gianluca, Borrelli Angela, Azzolini Federica, Fantozzi Roberta, Assogna Francesco, Conte Antonella, Centonze Diego
Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Unit of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, Pozzilli, Italy.
Ther Adv Neurol Disord. 2025 Jun 19;18:17562864251342855. doi: 10.1177/17562864251342855. eCollection 2025.
Multiple sclerosis (MS) is an autoimmune condition characterized by inflammatory demyelination that leads to irreversible neurological damage within the central nervous system (CNS). This review examines the therapeutic potential and clinical efficacy of cladribine tablets (CladT) for treating MS, focusing on the immune reconstitution mechanism and CNS effects. CladT represents a notable advance among disease-modifying therapies for MS due to its selective targeting of lymphocytes, resulting in sustained yet reversible immune modulation. This action leads to a substantial reduction in memory B cells while preserving the innate immune system and maintaining immunoglobulin levels, thereby mitigating the risks of secondary autoimmunity and infection. Cladribine appears to penetrate the blood-brain barrier, as indicated by cerebrospinal fluid (CSF) studies from parenteral cladribine use. In MS, CladT is associated with reductions in CSF immunological markers, such as oligoclonal bands and neurofilament light chain levels; it also mitigates acute and chronic inflammation, as evidenced, respectively, by consistent reductions in unique active lesions, and significant decrease in slowly expanding lesions in patients with predominant grey matter damage. These findings underscore the potential of CladT in reducing disability accumulation and improving long-term clinical outcomes in patients with highly active disease. By synthesizing data from clinical trials and real-world studies, this review underscores the effectiveness of CladT in reducing relapse rates, disability progression and magnetic resonance imaging-detected disease activity and emphasizes the importance of early high-efficacy treatment for optimizing long-term outcomes. Furthermore, emerging biomarkers are discussed as potential tools for predicting individual responses to therapy, thereby enabling more personalized treatment strategies. This review also provides valuable insights into the positive impact of CladT on quality of life measures, long-term outcomes and safety profile, all of which support the use of CladT in the evolving landscape of MS management.
多发性硬化症（MS）是一种自身免疫性疾病，其特征为炎症性脱髓鞘，可导致中枢神经系统（CNS）内不可逆转的神经损伤。本综述探讨了克拉屈滨片（CladT）治疗MS的治疗潜力和临床疗效，重点关注免疫重建机制和对CNS的影响。CladT在MS疾病修饰疗法中代表了一项显著进展，因为它能选择性地靶向淋巴细胞，从而实现持续但可逆的免疫调节。这一作用导致记忆B细胞大幅减少，同时保留先天免疫系统并维持免疫球蛋白水平，从而降低继发性自身免疫和感染的风险。正如肠胃外使用克拉屈滨的脑脊液（CSF）研究所示，克拉屈滨似乎能够穿透血脑屏障。在MS中，CladT与CSF免疫标志物减少有关，如寡克隆带和神经丝轻链水平；它还能减轻急性和慢性炎症，分别表现为独特的活动性病变持续减少，以及在主要灰质损伤患者中缓慢扩展病变显著减少。这些发现强调了CladT在减少高活动性疾病患者残疾累积和改善长期临床结局方面的潜力。通过综合临床试验和真实世界研究的数据，本综述强调了CladT在降低复发率、残疾进展和磁共振成像检测到的疾病活动方面的有效性，并强调了早期高效治疗对优化长期结局的重要性。此外还讨论了新兴生物标志物作为预测个体治疗反应的潜在工具，从而实现更个性化的治疗策略。本综述还提供了关于CladT对生活质量指标、长期结局和安全性的积极影响的宝贵见解，所有这些都支持在不断发展的MS管理中使用CladT。
