Abstract：
OBJECTIVE: 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.
METHODS: 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 T2-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 T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs).
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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 T2-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 T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs).
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目标：在多发性硬化症（MS）中，MRI标记物可以测量芬戈莫德的潜在神经保护作用，超出其抗炎活性。在这项研究中，我们旨在全面探索，在真实单词设置中，芬戈莫德是否不仅减少临床/MRI炎症活动，但也影响复发缓解型[RR]MS患者不可逆局灶性和全脑损害的进展。
方法：“进化”研究，24个月的观察,prospective,单臂,多中心研究，纳入261例RRMS患者,这些患者在32个意大利MS中心开始使用fingolimod,并接受了每两年一次的神经系统评估和每年一次的MRI评估.研究结果包括24个月时可评估的RRMS患者的比例：（1）没有新的/扩大的T2-高强度白质（WM）病变和/或临床复发；（2）“无疾病活动证据4”（“修改的NEDA-4”）的修改分类定义为没有新的/扩大的T2-高强度WM病变，临床复发，和6个月确认的残疾进展，T2-FLAIR图像的年侧脑室容积变化百分比<2%;(3)基线时和第12个月时活动性病变少于40%,演变为永久性黑洞(PBHs)。
结果：在第24个月，76/160（47.5％;95％置信区间[CI]=39.8％;55.2％）RRMS患者没有临床/MRI活动。170例RRMS患者中有39例（22.9%；95%CI=16.6%；29.3%）达到“改良NEDA-4”状态。72例RRMS患者中有44例（61.1％；95％CI=49.8％；72.4％）的活动性WM病变演变为PBH的比例不到40％。该研究证实了芬戈莫德的既定安全性和耐受性。
结论：通过将我们的结果与文献中的结果进行比较，进化研究似乎表明芬戈莫德的神经保护作用，限制炎症活动，脑萎缩和PBH发育。
方法：“进化”研究，24个月的观察,prospective,单臂,多中心研究，纳入261例RRMS患者,这些患者在32个意大利MS中心开始使用fingolimod,并接受了每两年一次的神经系统评估和每年一次的MRI评估.研究结果包括24个月时可评估的RRMS患者的比例：（1）没有新的/扩大的T2-高强度白质（WM）病变和/或临床复发；（2）“无疾病活动证据4”（“修改的NEDA-4”）的修改分类定义为没有新的/扩大的T2-高强度WM病变，临床复发，和6个月确认的残疾进展，T2-FLAIR图像的年侧脑室容积变化百分比<2%;(3)基线时和第12个月时活动性病变少于40%,演变为永久性黑洞(PBHs)。
结果：在第24个月，76/160（47.5％;95％置信区间[CI]=39.8％;55.2％）RRMS患者没有临床/MRI活动。170例RRMS患者中有39例（22.9%；95%CI=16.6%；29.3%）达到“改良NEDA-4”状态。72例RRMS患者中有44例（61.1％；95％CI=49.8％；72.4％）的活动性WM病变演变为PBH的比例不到40％。该研究证实了芬戈莫德的既定安全性和耐受性。
结论：通过将我们的结果与文献中的结果进行比较，进化研究似乎表明芬戈莫德的神经保护作用，限制炎症活动，脑萎缩和PBH发育。
