阿仑单抗6年的疗效与安全性：4年CARE-MS扩展试验的最终结果
Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.
作者信息
Coles Alasdair J, Arnold Douglas L, Bass Ann D, Boster Aaron L, Compston D Alastair S, Fernández Óscar, Havrdová Eva Kubala, Nakamura Kunio, Traboulsee Anthony, Ziemssen Tjalf, Jacobs Alan, Margolin David H, Huang Xiaobi, Daizadeh Nadia, Chirieac Madalina C, Selmaj Krzysztof W
机构信息
Department of Clinical Neurosciences, University of Cambridge, Box 165, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
NeuroRx Research, Montréal, Québec, Canada.
出版信息
Ther Adv Neurol Disord. 2021 Apr 23;14:1756286420982134. doi: 10.1177/1756286420982134. eCollection 2021.
BACKGROUND
In the 2-year CARE-MS I and II trials, alemtuzumab 12 mg administered on 5 consecutive days at core study baseline and on 3 consecutive days 12 months later significantly improved outcomes subcutaneous interferon beta-1a (SC IFNB-1a) in relapsing-remitting multiple sclerosis patients. Here, we present the final 6-year CARE-MS extension trial results (CAMMS03409), and compare outcomes over 6 years in patients randomized to both treatment groups at core study baseline.
METHODS
Over a 4-year extension, alemtuzumab patients (alemtuzumab-only) received as-needed additional alemtuzumab (⩾12 months apart) for disease activity after course 2. SC IFNB-1a patients who entered the extension discontinued SC IFNB-1a and received 2 alemtuzumab 12 mg courses (IFN-alemtuzumab), followed by additional, as-needed, alemtuzumab.
RESULTS
Through year 6, 63% of CARE-MS I and 50% of CARE-MS II alemtuzumab-only patients received neither additional alemtuzumab nor other disease-modifying therapy, with lasting suppression of disease activity, improved disability, and slowing of brain volume loss (BVL). In CARE-MS I patients (treatment-naive; less disability; shorter disease duration), disease activity and BVL were significantly reduced in IFN-alemtuzumab patients, similar to alemtuzumab-only patients at year 6. Among CARE-MS II patients (inadequate response to prior treatment; more disability; longer disease duration), alemtuzumab significantly improved clinical and magnetic resonance imaging outcomes, including BVL, in IFN-alemtuzumab patients; however, disability outcomes were less favorable alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups.
CONCLUSION
This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups.
CLINICALTRIALSGOV IDENTIFIERS
NCT00530348; NCT00548405; NCT00930553.
背景
在为期2年的CARE-MS I和II试验中，复发缓解型多发性硬化症患者在核心研究基线连续5天给予12毫克阿仑单抗，并在12个月后连续3天给药，其疗效显著优于皮下注射干扰素β-1a（SC IFNB-1a）。在此，我们展示了CARE-MS扩展试验的最终6年结果（CAMMS03409），并比较了在核心研究基线随机分配到两个治疗组的患者6年期间的疗效。
方法
在为期4年的扩展期内，阿仑单抗组患者（仅使用阿仑单抗）在第2疗程后根据疾病活动情况按需额外给予阿仑单抗（间隔至少12个月）。进入扩展期的SC IFNB-1a组患者停用SC IFNB-1a，接受2个疗程的12毫克阿仑单抗（IFN-阿仑单抗）治疗，随后按需额外给予阿仑单抗。
结果
到第6年，CARE-MS I中63%仅使用阿仑单抗的患者和CARE-MS II中50%仅使用阿仑单抗的患者既未接受额外的阿仑单抗治疗，也未接受其他疾病修饰治疗，疾病活动得到持续抑制，残疾状况改善，脑容量损失（BVL）减缓。在CARE-MS I患者（未接受过治疗；残疾程度较轻；病程较短）中，IFN-阿仑单抗组患者的疾病活动和BVL显著降低，与第6年时仅使用阿仑单抗的患者相似。在CARE-MS II患者（对先前治疗反应不佳；残疾程度较重；病程较长）中，阿仑单抗在IFN-阿仑单抗组患者中显著改善了临床和磁共振成像结果，包括BVL；然而，残疾状况的改善不如仅使用阿仑单抗的患者。两个治疗组在接受阿仑单抗治疗后的安全性概况，包括感染和自身免疫情况相似。
结论
本研究证明了阿仑单抗在6年期间具有高效性，且两个治疗组的安全性概况相似。
临床试验注册号
NCT00530348；NCT00548405；NCT00930553。
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