Havrdova Eva, Arnold Douglas L, Cohen Jeffrey A, Hartung Hans-Peter, Fox Edward J, Giovannoni Gavin, Schippling Sven, Selmaj Krzysztof W, Traboulsee Anthony, Compston D Alastair S, Margolin David H, Thangavelu Karthinathan, Rodriguez Claudio E, Jody Darlene, Hogan Richard J, Xenopoulos Panos, Panzara Michael A, Coles Alasdair J
From the Department of Neurology and Center for Clinical Neuroscience (E.H.), First Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada; Mellen Center (J.A.C.), Cleveland Clinic, OH; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; MS Clinic of Central Texas (E.J.F.), Central Texas Neurology Consultants, Round Rock; Queen Mary University of London (G.G.), Barts and The London School of Medicine, UK; Neuroimmunology and Multiple Sclerosis Research (S.S.), Department of Neurology, University Hospital Zürich and University of Zürich, Switzerland; Department of Neurology (K.W.S.), Medical University of Łódź, Poland; The University of British Columbia (A.T.), Vancouver, Canada; Department of Clinical Neurosciences (D.A.S.C., A.J.C.), University of Cambridge, UK; Sanofi (D.H.M., K.T., C.E.R., D.J., M.A.P.), Cambridge, MA; Evidence Scientific Solutions (R.J.H.), Sydney, NSW, Australia; and Evidence Scientific Solutions (P.X.), Philadelphia, PA. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.
Neurology. 2017 Sep 12;89(11):1107-1116. doi: 10.1212/WNL.0000000000004313. Epub 2017 Aug 23.
To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348).
Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs).
Most alemtuzumab-treated patients (95.1%) completing CARE-MS I enrolled in the extension; 68.5% received no additional alemtuzumab treatment. ARR remained low in years 3, 4, and 5 (0.19, 0.14, and 0.15). Over years 0-5, 79.7% were free of 6-month CDW; 33.4% achieved 6-month CDI. Most patients (61.7%, 60.2%, and 62.4%) had NEDA in years 3, 4, and 5. Median yearly BVL improved over years 2-4, remaining low in year 5 (years 1-5: -0.59%, -0.25%, -0.19%, -0.15%, and -0.20%). Exposure-adjusted incidence rates of most AEs declined in the extension relative to the core study. Thyroid disorder incidences peaked at year 3 and subsequently declined.
Based on these data, alemtuzumab provides durable efficacy through 5 years in the absence of continuous treatment, with most patients not receiving additional courses.
NCT00530348; NCT00930553.
This study provides Class III evidence that alemtuzumab durably improves efficacy outcomes and slows BVL in patients with RRMS.
评估阿仑单抗治疗初治复发缓解型多发性硬化症（RRMS）患者（CARE-MS I；NCT00530348）的5年疗效和安全性。
接受阿仑单抗治疗的患者在基线时和12个月后接受治疗疗程；在核心研究结束后，他们可进入扩展研究（NCT00930553），根据需要接受阿仑单抗再治疗以应对复发或MRI活动。评估指标包括年化复发率（ARR）、6个月确诊的残疾恶化（CDW；扩展残疾状态量表[EDSS]评分增加≥1分[若基线EDSS = 0，则增加≥1.5分]）、6个月确诊的残疾改善（CDI；EDSS评分降低≥1分[基线评分≥2.0]）、无疾病活动证据（NEDA）、脑容量损失（BVL）和不良事件（AE）。
大多数完成CARE-MS I的接受阿仑单抗治疗的患者（95.1%）进入了扩展研究；68.5%的患者未接受额外的阿仑单抗治疗。第3、4和5年的ARR仍较低（分别为0.19、0.14和0.15）。在0至5年期间，79.7%的患者6个月内无CDW；33.4%的患者实现了6个月CDI。大多数患者（第3、4和5年分别为61.7%、60.2%和62.4%）达到NEDA。第2至4年的年均BVL中位数有所改善，第5年仍较低（第1至5年分别为-0.59%、-0.25%、-0.19%、-0.15%和-0.20%）。与核心研究相比，扩展研究中大多数AE的暴露调整发病率有所下降。甲状腺疾病发病率在第3年达到峰值，随后下降。
基于这些数据，在无持续治疗的情况下，阿仑单抗在5年内提供持久疗效，大多数患者未接受额外疗程。
NCT00530348；NCT00930553。
本研究提供了III级证据，表明阿仑单抗可持久改善RRMS患者的疗效结局并减缓BVL。
