Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial
Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial
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DOI：
10.1016/s0140-6736(12)61768-1
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发表时间：
2012-11-24
期刊：
影响因子：
168.9
通讯作者：
Compston, D. Alastair S.
中科院分区：
文献类型：
--
作者：
Coles, Alasdair J.;Twyman, Cary L.;Compston, D. Alastair S.
抗cd52单克隆抗体阿仑妥珠单抗可降低先前未经治疗的复发缓解型多发性硬化症患者的疾病活动性。我们的目的是评估阿仑单抗与干扰素β 1a在一线治疗后复发患者中的疗效和安全性。方法：在我们为期2年的随机对照3期试验中，我们招募了年龄在18-55岁的复发缓解型多发性硬化症患者，并且至少有一次使用干扰素β或格拉替雷治疗复发。符合条件的参与者通过交互式语音应答系统按1:2:2的比例随机分配，按部位分层，接受皮下干扰素β 1a 44 μ g，静脉注射阿仑单抗12 mg /天，或静脉注射阿仑单抗24 mg /天。干扰素β 1a每周给药3次，阿仑单抗每天给药1次，基线时5天，12个月时3天。24毫克/天的组被停止以帮助招募，但数据被纳入安全性评估。主要终点是复发率和到6个月持续残疾积累的时间，在所有接受至少一剂研究药物的患者中比较阿仑单抗12mg和干扰素β 1a。本研究已在ClinicalTrials.gov注册，注册号NCT00548405。结果随机分配干扰素β 1a的231例患者中有202例（87%）和随机分配阿仑单抗12mg的436例患者中有426例（98%）被纳入初步分析。干扰素β 1a组104例（51%）患者复发（201例），而阿仑单抗组147例（35%）患者复发（236例）；发生率比0.51 [95% CI 0.39-0.65]
Background The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. We aimed to assess efficacy and safety of alemtuzumab compared with interferon beta 1a in patients who have relapsed despite first-line treatment.Methods In our 2 year, rater-masked, randomised controlled phase 3 trial, we enrolled adults aged 18-55 years with relapsing-remitting multiple sclerosis and at least one relapse on interferon beta or glatiramer. Eligible participants were randomly allocated in a 1: 2: 2 ratio by an interactive voice response system, stratified by site, to receive subcutaneous interferon beta 1a 44 mu g, intravenous alemtuzumab 12 mg per day, or intravenous alemtuzumab 24 mg per day. Interferon beta 1a was given three-times per week and alemtuzumab was given once per day for 5 days at baseline and for 3 days at 12 months. The 24 mg per day group was discontinued to aid recruitment, but data are included for safety assessments. Coprimary endpoints were relapse rate and time to 6 month sustained accumulation of disability, comparing alemtuzumab 12 mg and interferon beta 1a in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00548405.Findings 202 (87%) of 231 patients randomly allocated interferon beta 1a and 426 (98%) of 436 patients randomly allocated alemtuzumab 12 mg were included in the primary analyses. 104 (51%) patients in the interferon beta 1a group relapsed (201 events) compared with 147 (35%) patients in the alemtuzumab group (236 events; rate ratio 0.51 [95% CI 0.39-0.65]; p