阿仑单抗治疗复发型多发性硬化症（CARE-MS II）5年随访：疗效与安全性结果
Alemtuzumab CARE-MS II 5-year follow-up: Efficacy and safety findings.
作者信息
Coles Alasdair J, Cohen Jeffrey A, Fox Edward J, Giovannoni Gavin, Hartung Hans-Peter, Havrdova Eva, Schippling Sven, Selmaj Krzysztof W, Traboulsee Anthony, Compston D Alastair S, Margolin David H, Thangavelu Karthinathan, Chirieac Madalina C, Jody Darlene, Xenopoulos Panos, Hogan Richard J, Panzara Michael A, Arnold Douglas L
机构信息
From the Department of Clinical Neurosciences (A.J.C., D.A.S.C.), University of Cambridge, UK; Mellen Center (J.A.C.), Cleveland Clinic, OH; 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; Department of Neurology and Center for Neuropsychiatry (H.-P.H.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology and Center for Clinical Neuroscience (E.H.), First Faculty of Medicine, Charles University and General Hospital in Prague, Czech Republic; Neuroimmunology and Multiple Sclerosis Research, Department of Neurology (S.S.), 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; Sanofi (D.H.M., K.T., M.C.C., D.J., M.A.P.), Cambridge, MA; Envision Scientific Solutions (P.X.), Philadelphia, PA; Envision Scientific Solutions (R.J.H.), Sydney, NSW, Australia; NeuroRx Research (D.L.A.), Montréal; Department of Neurology and Neurosurgery (D.L.A.), Montréal Neurological Institute, McGill University, Québec, Canada. M.A.P. is currently affiliated with Wave Life Sciences, Cambridge, MA.
出版信息
Neurology. 2017 Sep 12;89(11):1117-1126. doi: 10.1212/WNL.0000000000004354. Epub 2017 Aug 23.
OBJECTIVE
To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.
METHODS
In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. 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) were assessed.
RESULTS
Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3-5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1-5: -0.48%, -0.22%, -0.10%, -0.19%, -0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter.
CONCLUSIONS
Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.
目的
评估阿仑单抗对先前治疗反应不佳的复发缓解型多发性硬化症患者的5年疗效及安全性。
方法
在为期2年的阿仑单抗与利比（Rebif）治疗多发性硬化症疗效比较（CARE-MS）II研究（NCT00548405）中，接受阿仑单抗治疗的患者接受2个疗程（基线期及12个月后）治疗。患者可进入扩展研究（NCT00930553），根据需要接受阿仑单抗再治疗以应对复发或磁共振成像（MRI）活动。评估年化复发率（ARR）、6个月确认的残疾恶化（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个月确认的残疾改善（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）及不良事件（AE）。
结果
完成CARE-MS II研究的大多数接受阿仑单抗治疗的患者（92.9%）进入扩展研究；59.8%的患者未接受阿仑单抗再治疗。每个扩展年的ARR均较低（第3 - 5年：0.22、0.23、0.18）。至5年时，75.
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