Bass Ann D, Arroyo Rafael, Boster Aaron L, Boyko Alexey N, Eichau Sara, Ionete Carolina, Limmroth Volker, Navas Carlos, Pelletier Daniel, Pozzilli Carlo, Ravenscroft Jennifer, Sousa Livia, Tintoré Mar, Uitdehaag Bernard M J, Baker Darren P, Daizadeh Nadia, Choudhry Zia, Rog David
Neurology Center of San Antonio, 1314 East Sonterra Blvd #601, San Antonio, TX, USA.
Hospital Universitario Quirónsalud Madrid (RA), c/ Diego de Velázquez, 1 28223 Pozuelo de Alarcón, Madrid, Spain.
Mult Scler Relat Disord. 2021 Apr;49:102717. doi: 10.1016/j.msard.2020.102717. Epub 2020 Dec 24.
Alemtuzumab significantly improved clinical and MRI outcomes vs. subcutaneous interferon beta-1a (SC IFNB-1a) in the CARE-MS trials (NCT00530348, NCT00548405), with sustained efficacy in 2 consecutive extensions (NCT00930553, NCT02255656 [TOPAZ]).
Post hoc analysis of 8-year alemtuzumab efficacy and safety in pooled CARE-MS patients (N=811) stratified by baseline age (≥18 to ≤25, >25 to ≤35, >35 to ≤45, >45 to ≤55 years).
Compared with SC IFNB-1a over 2 years across age cohorts, alemtuzumab lowered annualized relapse rates (ARR; 0.22-0.24 vs. 0.38-0.51), improved or stabilized disability (freedom from 6-month confirmed disability worsening [CDW]: 85%-92% vs. 62%-88%; achievement of 6-month confirmed disability improvement [CDI]: 20%-31% vs. 13%-25%), increased proportions free of MRI disease activity (70%-86% vs. 42%-63% per year), and slowed brain volume loss (BVL; -0.45% to -0.87% vs. -0.50% to -1.39%). Through Year 2, the treatment effect with alemtuzumab did not significantly differ among age groups for ARR (p-interaction=0.6325), 6-month CDW-free (p-interaction=0.4959), 6-month CDI (p-interaction=0.9268), MRI disease activity-free (p-interaction=0.6512), and BVL (p-interaction=0.4970). Alemtuzumab remained effective on outcomes through Year 8 across age groups. Age-related increases in malignancies (≤45 years: 0.9%-2.2% vs. >45 years: 8.1%) and deaths (0%-1.7% vs. 7.0%) were observed. Serious infections also increased from the youngest (5.1%) to oldest (12.8%) age cohorts.
Alemtuzumab had greater efficacy than SC IFNB-1a over 2 years across comparable age groups, with no significant differences between alemtuzumab-treated age groups. Efficacy on relapse, disability, and MRI outcomes continued through Year 8 across age groups. Age-related increases in serious infections, malignancies, and deaths were observed.
在CARE-MS试验（NCT00530348、NCT00548405）中，与皮下注射干扰素β-1a（SC IFNB-1a）相比，阿仑单抗显著改善了临床和MRI结果，并且在两项连续的扩展试验（NCT00930553、NCT02255656 [TOPAZ]）中具有持续疗效。
对CARE-MS合并患者（N = 811）进行事后分析，根据基线年龄（≥18至≤25岁、>25至≤35岁、>35至≤45岁、>45至≤55岁）进行分层，分析阿仑单抗8年的疗效和安全性。
在各年龄组中，与2年的SC IFNB-1a相比，阿仑单抗降低了年化复发率（ARR；0.22 - 0.24对0.38 - 0.51），改善或稳定了残疾状况（6个月确认残疾无恶化[CDW]的比例：85% - 92%对62% - 88%；6个月确认残疾改善[CDI]的比例：20% - 31%对13% - 25%），增加了无MRI疾病活动的比例（每年70% - 86%对42% - 63%），并减缓了脑容量损失（BVL；-0.45%至-0.87%对-0.50%至-1.39%）。到第2年，阿仑单抗在各年龄组中的治疗效果在ARR（p交互作用 = 0.6325）、6个月无CDW（p交互作用 = 0.4959）、6个月CDI（p交互作用 = 0.9268）、无MRI疾病活动（p交互作用 = 0.6512）和BVL（p交互作用 = 0.4970）方面无显著差异。阿仑单抗在各年龄组中直至第8年对各项结果均保持有效。观察到恶性肿瘤（≤45岁：0.9% - 2.2%对>45岁：8.1%）和死亡（0% - 1.7%对7.0%）随年龄增长而增加。严重感染也从最年轻年龄组（5.1%）到最年长年龄组（12.8%）有所增加。
在各可比年龄组中，阿仑单抗在2年期间的疗效优于SC IFNB-1a，接受阿仑单抗治疗的年龄组之间无显著差异。各年龄组直至第8年在复发、残疾和MRI结果方面的疗效持续存在。观察到严重感染、恶性肿瘤和死亡随年龄增长而增加。
