Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Hematology and Transplant Center, Ospedale Policlinico San Martino, IRCSS, Genoa, Italy.
Eur J Neurol. 2020 Oct;27(10):2047-2055. doi: 10.1111/ene.14324. Epub 2020 Jun 16.
The best therapeutic approach for aggressive relapsing-remitting multiple sclerosis remains unknown. The objective was to compare the efficacy and safety of autologous haematopoietic stem cell transplantation (aHSCT) and alemtuzumab in aggressive relapsing-remitting multiple sclerosis.
The time to first relapse, time to confirmed disability worsening, time to first evidence of magnetic resonance imaging (MRI) activity and time to first evidence of disease activity were compared between the two treatment groups. Secondary outcomes included the 12, 24 and 36 month annualized relapse rate (ARR) and the 6-month confirmed Expanded Disability Status Scale (EDSS) changes at months 12 and 24.
Fifty-seven patients treated with aHSCT (n = 25) or alemtuzumab (n = 32) were included. At baseline, aHSCT patients had a higher EDSS (median score 6 vs. 3; P < 0.001), higher ARR (mean ARR 3.2 vs. 1.7; P = 0.001) and a higher number of baseline T1 gadolinium-enhancing lesions on MRI (mean number 15.5 vs. 1.6; P < 0.001). NEDA-3 (no evidence of disease activity) status was more frequently achieved in aHSCT-treated patients than in alemtuzumab-treated patients [75% vs. 56% of patients at the end of the observation period; hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.08-0.84; P = 0.023]. aHSCT significantly reduced the risk of relapse (relapse-free survival 84% vs. 69%; HR 0.13, 95% CI 0.02-0.63; P = 0.012) and MRI activity (MRI-activity-free survival 85% vs. 59%; HR 0.13, 95% CI 0.03-0.59; P = 0.009). The ARR at 36 months was significantly lower in the aHSCT group (0.05 vs. 0.35, P = 0.02). A significant effect of aHSCT in promoting EDSS improvement compared with alemtuzumab was noted (P = 0.035).
Alemtuzumab and aHSCT are effective treatment choices for aggressive multiple sclerosis. aHSCT seems to be superior to alemtuzumab in inducing complete disease control and in promoting short-term disability improvement.
目前仍不清楚侵袭性复发缓解型多发性硬化症的最佳治疗方法。本研究旨在比较自体造血干细胞移植（aHSCT）和阿仑单抗治疗侵袭性复发缓解型多发性硬化症的疗效和安全性。
比较两组患者的首次复发时间、确诊残疾进展时间、首次磁共振成像（MRI）活动证据时间和首次疾病活动证据时间。次要结局包括治疗后 12、24 和 36 个月的年化复发率（ARR）和治疗后 12 个月及 24 个月时的 6 个月确认扩展残疾状态量表（EDSS）变化。
共纳入 57 例接受 aHSCT（n=25）或阿仑单抗（n=32）治疗的患者。基线时，aHSCT 患者的 EDSS 评分较高（中位数 6 分 vs. 3 分；P<0.001）、ARR 较高（平均 ARR 3.2 分 vs. 1.7 分；P=0.001）、基线 MRI 上 T1 钆增强病变较多（平均数量 15.5 个 vs. 1.6 个；P<0.001）。与阿仑单抗治疗组相比，aHSCT 治疗组患者达到无疾病活动状态（NEDA-3）的比例更高[观察期结束时分别为 75%和 56%的患者；风险比（HR）0.27，95%置信区间（CI）0.08-0.84；P=0.023]。aHSCT 可显著降低复发风险（无复发生存 84% vs. 69%；HR 0.13，95%CI 0.02-0.63；P=0.012）和 MRI 活动证据风险（MRI 无活动生存 85% vs. 59%；HR 0.13，95%CI 0.03-0.59；P=0.009）。aHSCT 组 36 个月时的 ARR 显著较低（0.05 分 vs. 0.35 分；P=0.02）。与阿仑单抗相比，aHSCT 可显著改善 EDSS（P=0.035）。
阿仑单抗和 aHSCT 是侵袭性多发性硬化症的有效治疗选择。与阿仑单抗相比，aHSCT 似乎更能诱导完全疾病控制和促进短期残疾改善。
