UNASSIGNED: To assess basic characteristics, therapeutic effects, and prognostic biomarkers on clinical and imaging parameters of disease activity for relapsing-remitting MS (RRMS) patients selected for ALZ, in a real-world long-term setting.
UNASSIGNED: Fifty-one RRMS patients [female = 31; mean age 36 (standard deviation 7.1) years; median expanded disability status scale (EDSS) 2 (interquartile range (IQR) 1.5)] initiating ALZ treatment, were consecutively included. Patients were assessed at baseline and thereafter annually for 5 years with clinical measures, symbol digit modality test (SDMT), and magnetic resonance imaging (MRI). Concentrations of glial fibrillary acidic protein (GFAP), reflecting astrogliosis, and neurofilament light (NfL), reflecting axonal damage, were measured in cerebrospinal fluid (CSF) and serum samples collected at baseline and after 2 years in CSF, and annually in serum. Control subjects were symptomatic controls (SCs, n = 27), who were examined at baseline and after 5 years without evidence of neurological disease.
UNASSIGNED: While the mean annualized relapse rate was significantly reduced from baseline at each year of follow-up, disability was essentially maintained at a median EDSS of 1.5 and IQR between 1.13 and 2.25. New MRI activity was recorded in 26 patients (53%) over 5 years. The proportion of patients who achieved no evidence of disease activity (NEDA-3), 6-months confirmed disability worsening (CDW), and 6-months confirmed disability improvement (CDI) at 5 years were 33, 31, and 31%, respectively. The SDMT score was reduced for patients (p < 0.001), but unchanged for SCs. ALZ treatment did not change GFAP levels, whereas there was a significant decrease for RRMS patients in median CSF and serum NfL levels at follow-up [CSF month 24: 456 pg./mL (IQR 285.4) (p = 0.05); serum month 24: 6.7 pg/mL (IQR 4.7) (p < 0.01); serum month 60: 7.2 pg/mL (IQR 4.7) (p < 0.01)], compared to baseline [CSF: 1014 pg/mL (IQR 2832.5); serum 8.6 pg/mL (IQR 17.4)].
UNASSIGNED: In this real-world mono-center population, we observed a progression-free survival of 69%, cumulative NEDA-3 of 33%, and reduced NfL levels, over a five-year follow-up. This confirms ALZ as an effective pulsed immune reconstitution therapy that significantly reduces neuro axonal loss, and therefore has the potential to reduce long-term neurological disability. ALZ did not appear to affect astrogliosis.
■要评估基本特征,治疗效果,以及选择ALZ的复发缓解型MS(RRMS)患者疾病活动的临床和影像学参数的预后生物标志物,在现实世界的长期环境中。
■51例RRMS患者[女性=31;平均年龄36(标准差7.1)岁;中位数扩展残疾状态量表(EDSS)2(四分位距(IQR)1.5)]开始ALZ治疗,被连续包括在内。患者在基线时进行评估,此后每年进行5年的临床测量,符号数字模态测试(SDMT),磁共振成像(MRI)。胶质纤维酸性蛋白(GFAP)的浓度,反映星形胶质增生,和神经丝光(NfL),反射轴突损伤,在基线时和2年后在脑脊液中收集的脑脊液(CSF)和血清样本中进行测量,每年都在血清中。对照受试者为症状对照(SCs,n=27),他们在基线和5年后接受检查,没有神经系统疾病的证据。
■虽然在每年的随访中,平均年复发率从基线显着降低,残疾基本上维持在中位数EDSS为1.5,IQR在1.13和2.25之间。在5年内,有26例患者(53%)记录了新的MRI活动。没有疾病活动证据的患者比例(NEDA-3),6个月确认残疾恶化(CDW),和6个月确认的残疾改善(CDI)在5年分别为33%,31%和31%,分别。患者的SDMT评分降低(p<0.001),但SC不变。ALZ治疗没有改变GFAP水平,而RRMS患者在随访时的中位CSF和血清NfL水平显着降低[CSF月24:456pg./mL(IQR285.4)(p=0.05);血清第24个月:6.7pg/mL(IQR4.7)(p<0.01);血清第60个月:7.2pg/mL(IQR4.7)(p<0.01)],与基线相比[CSF:1014pg/mL(IQR2832.5);血清8.6pg/mL(IQR17.4)]。
■在这个现实世界的单中心人口中,我们观察到无进展生存率为69%,累计33%的NEDA-3,降低了NFL水平,五年的随访。这证实了ALZ是一种有效的脉冲免疫重建疗法,可显着减少神经轴突损失,因此有可能减少长期的神经残疾。ALZ似乎不影响星形胶质细胞增生。