Kolb Hadar, Shachaf Yuval, Fainberg Karin, Golan Maya, Regev Keren, Vigiser Ifat, Fuchs Lior, Gadoth Avi, Kestenbaum Meir, Omer Nurit, Shopin Ludmila, Ash Elissa L, Artzi Moran, Ben Bashat Dafna, Aizenstein Orna, Karni Arnon
Neuroimmunology and Multiple Sclerosis Unit, Neurology Division, Neurology Institute, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 6423906, Tel Aviv, Israel.
Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
J Neurol. 2025 May 4;272(5):374. doi: 10.1007/s00415-025-13114-z.
Progressive multiple sclerosis (PMS) remains challenging to treat effectively. Intrathecal methotrexate (ITMTX) has emerged as a potential therapy for alleviating PMS symptoms. This study aimed to assess the safety, tolerability, and efficacy of ITMTX in PMS patients over short- and long-term periods. A 1-year, open-label, phase 1 study was conducted, administering ITMTX quarterly to eligible PMS patients. Primary endpoints included changes in Expanded Disability Status Scale (EDSS) scores, 25-Foot Walk (25FW), and Symbol Digit Modalities Test (SDMT) from baseline to 1 year. Secondary endpoints encompassed 6-month clinical changes, cerebrospinal fluid immune cell profiling, and MRI measures. Long-term follow-up included retrospective review of patients continuing ITMTX treatment beyond the initial study period. Twenty-two patients were initially enrolled, with 17 completing the 12-month treatment. ITMTX was well-tolerated, with post-LP headache being the most common adverse event (31.8%). No significant changes were observed in EDSS, 25FW, SDMT, CSF IgG levels, or immune cell counts over 12 months. Long-term follow-up of ten patients receiving ITMTX for 2-9 years (mean 4.1 ± 3.1 years) showed stable EDSS in seven patients, with three experiencing minimal worsening (0.5 points). The therapy was well-tolerated long-term, with no evidence of disease progression in most patients. These findings support ITMTX as a promising therapeutic approach for PMS, particularly for patients progressing despite approved disease-modifying therapies or unable to tolerate them. Further large-scale studies are warranted to confirm these results. Clinicaltrials.gov identifier: NCT02644044, year: 2015.
进行性多发性硬化症（PMS）的有效治疗仍然具有挑战性。鞘内注射甲氨蝶呤（ITMTX）已成为缓解PMS症状的一种潜在疗法。本研究旨在评估ITMTX在PMS患者短期和长期治疗中的安全性、耐受性和疗效。开展了一项为期1年的开放标签1期研究，每季度给符合条件的PMS患者注射ITMTX。主要终点包括从基线到1年时扩展残疾状态量表（EDSS）评分、25英尺步行试验（25FW）和符号数字模式测验（SDMT）的变化。次要终点包括6个月时的临床变化、脑脊液免疫细胞分析和MRI测量。长期随访包括对在初始研究期后继续接受ITMTX治疗的患者进行回顾性评估。最初纳入22例患者，其中17例完成了12个月的治疗。ITMTX耐受性良好，腰穿后头痛是最常见的不良事件（31.8%）。在12个月内，EDSS、25FW、SDMT、脑脊液IgG水平或免疫细胞计数均未观察到显著变化。对10例接受ITMTX治疗2 - 9年（平均4.1±3.1年）的患者进行长期随访，结果显示7例患者的EDSS稳定，3例患者病情轻微恶化（0.5分）。该疗法长期耐受性良好，大多数患者没有疾病进展的迹象。这些发现支持ITMTX作为一种有前景的PMS治疗方法，特别是对于那些尽管接受了批准的疾病修饰疗法但仍病情进展或无法耐受这些疗法的患者。有必要进行进一步的大规模研究来证实这些结果。Clinicaltrials.gov标识符：NCT02644044，年份：2015。
