Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study
Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study
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DOI：
10.1016/s0140-6736(08)61619-0
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发表时间：
2008-10-25
期刊：
影响因子：
168.9
通讯作者：
O'Neill, Gilmore N.
中科院分区：
文献类型：
--
作者：
Kappos, Ludwig;Gold, Ralf;O'Neill, Gilmore N.
背景口服富马酸盐（BG 00012）可能具有双重抗炎和神经保护作用。我们的目的是评估BG 00012在复发缓解型多发性硬化症患者中的疗效和安全性。方法257例复发缓解型多发性硬化症患者，年龄18-55岁，随机分配接受120 mg每日一次（n =64）、120 mg每日三次（n=64）或240 mg每日三次（n=64）BG 00012，或安慰剂（n=65）治疗24周。在安全性评估的24周延长期内，接受安慰剂治疗的患者接受BG 00012 240 mg每日3次治疗。主要终点为第12、16、20和24周时脑部MRI扫描发现的新钆增强（GdE）病变总数。其他终点包括新发GAE病变（第4-24周）、新发或扩大的T2高信号病变、第24周新发T1低信号病变的累积数量和年复发率。对疗效可评价人群进行分析。还评估了安全性和耐受性。该研究注册于ClinicalTrials.gov，编号NCT 00168701。结果与安慰剂相比，BG 00012 240 mg每日3次治疗可使第12周至第24周新发GdE病变的平均总数减少69%（1 . 4 vs 4.5，p
Background Oral fumarate (BG00012) might have dual anti-inflammatory and neuroprotective effects. Our aim was to assess the efficacy and safety of BG00012 in patients with relapsing-remitting multiple sclerosis.Methods 257 patients, aged 18-55 years, with relapsing-remitting multiple sclerosis were randomly assigned to receive 120 mg once daily (n=64), 120 mg three times daily (n=64), or 240 mg three times daily (n=64) BG00012, or placebo (n=65) for 24 weeks. During an extension period of 24 weeks for safety assessment, patients treated with placebo received BG00012 240 mg three times daily. The primary endpoint was total number of new gadolinium enhancing (GdE) lesions on brain MRI scans at weeks 12, 16, 20, and 24. Additional endpoints included cumulative number of new GAE lesions (weeks 4-24), new or enlarging T2-hyperintense lesions, new T1-hypointense lesions at week 24, and annualised relapse rate. Analysis was done on the efficacy-evaluable population. Safety and tolerability were also assessed. This study is registered with ClinicalTrials.gov, number NCT00168701.Findings Treatment with BG00012 240 mg three times daily reduced by 69% the mean total number of new GdE lesions from week 12 to 24 compared with placebo (1 . 4 vs 4.5, p