Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
J Neurol. 2024 Sep;271(9):6181-6196. doi: 10.1007/s00415-024-12590-z. Epub 2024 Jul 29.
In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients.
The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24 months: (1) no new/enlarging T-hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs).
At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod.
By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.
在多发性硬化症（MS）中，MRI 标志物可以测量芬戈莫德除了抗炎活性之外的潜在神经保护作用。在这项研究中，我们旨在全面探索，在真实环境中，芬戈莫德不仅是否不仅降低临床/ MRI 炎症活动，而且还影响复发性缓解型 [RR] MS 患者的不可逆转的局灶性和全脑损伤的进展。
“EVOLUTION”研究是一项为期 24 个月的观察性、前瞻性、单臂、多中心研究，招募了 261 名在 32 个意大利 MS 中心开始接受芬戈莫德治疗的 RRMS 患者，并进行了每半年一次的神经学评估和每年一次的 MRI 评估。研究结果包括在 24 个月时可评估的 RRMS 患者的比例：（1）无新发/扩大 T 高信号白质（WM）病变和/或临床复发；（2）一种改良的“无疾病活动 4 项标准”（“改良 NEDA-4”）定义为无新发/扩大 T 高信号 WM 病变、临床复发和 6 个月确认的残疾进展，以及每年 T-FLAIR 图像上侧脑室容积变化<2%；（3）基线和第 12 个月时有 40%以下的活动病变进展为永久性黑洞（PBHs）。
在第 24 个月时，160 名 RRMS 患者中有 76 名（47.5%；95%置信区间[CI] = 39.8%；55.2%）无临床/MRI 活动。170 名 RRMS 患者中有 39 名（22.9%；95% CI = 16.6%；29.3%）达到“改良 NEDA-4”状态。72 名 RRMS 患者中有 44 名（61.1%；95% CI = 49.8%；72.4%）有 40%以下的活动 WM 病变进展为 PBHs。研究证实了芬戈莫德已确立的安全性和耐受性特征。
通过将我们的结果与文献进行比较，EVOLUTION 研究似乎表明芬戈莫德具有神经保护作用，可限制炎症活动、脑萎缩和 PBH 发展。
