Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.
Efficacy and safety of alemtuzumab over 6 years: final results of the 4-year CARE-MS extension trial.
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DOI：
10.1177/1756286420982134
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发表时间：
2021
影响因子：
5.9
通讯作者：
Selmaj KW
中科院分区：
文献类型：
--
作者：
Coles AJ;Arnold DL;Bass AD;Boster AL;Compston DAS;Fernández Ó;Havrdová EK;Nakamura K;Traboulsee A;Ziemssen T;Jacobs A;Margolin DH;Huang X;Daizadeh N;Chirieac MC;Selmaj KW
在为期2年的CARE-MS I和II试验中，与皮下干扰素β -1a （SC IFNB-1a）相比，阿仑妥珠单抗12mg在核心研究基线连续5天和12个月后连续3天显著改善了复发-缓解型多发性硬化症患者的预后。在这里，我们提出了最终的6年CARE-MS扩展试验结果（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年的结果。在4年的延长期间，阿仑单抗患者（仅阿仑单抗）在疗程2后接受了根据需要额外的阿仑单抗（间隔12个月）。进入延长期的SC IFNB-1a患者停用SC IFNB-1a并接受2个阿仑妥珠单抗12mg疗程（ifn -阿仑妥珠单抗），随后根据需要接受额外的阿仑妥珠单抗。在第6年，63%的CARE-MS I和50%的CARE-MS II仅使用阿仑单抗的患者既没有接受额外的阿仑单抗治疗，也没有接受其他疾病改善治疗，持续抑制疾病活动，改善残疾，减缓脑容量损失（BVL）。在CARE-MS I患者（未接受治疗，致残率较低，病程较短）中，ifn -阿仑单抗患者的疾病活动性和BVL在第6年显著降低，与仅使用阿仑单抗的患者相似。在CARE-MS II患者（对先前治疗反应不足，残疾更多，病程更长）中，阿仑单抗显著改善了ifn -阿仑单抗患者的临床和磁共振成像结果，包括BVL；然而，与仅使用阿仑单抗的患者相比，残疾结局不太有利。阿仑单抗治疗组之间的安全性（包括感染和自身免疫）相似。这项研究证明了阿仑单抗在6年内的高疗效，在治疗组之间具有相似的安全性。NCT00530348;NCT00548405;NCT00930553
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 versus 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. 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. 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 versus alemtuzumab-only patients. Safety profiles, including infections and autoimmunities, following alemtuzumab were similar between treatment groups. This study demonstrates the high efficacy of alemtuzumab over 6 years, with a similar safety profile between treatment groups. NCT00530348; NCT00548405; NCT00930553