National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, UK; Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, University College London, London, UK; UCL Institute of Neurology, University College London, London, UK; Imperial College Healthcare NHS Trust, London, UK; Imperial College, London, UK.
UCL Institiute of Ophthalmology, University College London, London, UK.
Lancet. 2014 Jun 28;383(9936):2213-21. doi: 10.1016/S0140-6736(13)62242-4. Epub 2014 Mar 19.
Secondary progressive multiple sclerosis, for which no satisfactory treatment presently exists, accounts for most of the disability in patients with multiple sclerosis. Simvastatin, which is widely used for treatment of vascular disease, with its excellent safety profile, has immunomodulatory and neuroprotective properties that could make it an appealing candidate drug for patients with secondary progressive multiple sclerosis.
We undertook a double-blind, controlled trial between Jan 28, 2008, and Nov 4, 2011, at three neuroscience centres in the UK. Patients aged 18-65 years with secondary progressive multiple sclerosis were randomly assigned (1:1), by a centralised web-based service with a block size of eight, to receive either 80 mg of simvastatin or placebo. Patients, treating physicians, and outcome assessors were masked to treatment allocation. The primary outcome was the annualised rate of whole-brain atrophy measured from serial volumetric MRI. Analyses were by intention to treat and per protocol. This trial is registered with ClinicalTrials.gov, number NCT00647348.
140 participants were randomly assigned to receive either simvastatin (n=70) or placebo (n=70). The mean annualised atrophy rate was significantly lower in patients in the simvastatin group (0·288% per year [SD 0·521]) than in those in the placebo group (0·584% per year [0·498]). The adjusted difference in atrophy rate between groups was -0·254% per year (95% CI -0·422 to -0·087; p=0·003); a 43% reduction in annualised rate. Simvastatin was well tolerated, with no differences between the placebo and simvastatin groups in proportions of participants who had serious adverse events (14 [20%] vs nine [13%]).
High-dose simvastatin reduced the annualised rate of whole-brain atrophy compared with placebo, and was well tolerated and safe. These results support the advancement of this treatment to phase 3 testing.
The Moulton Foundation [charity number 1109891], Berkeley Foundation [268369], the Multiple Sclerosis Trials Collaboration [1113598], the Rosetrees Trust [298582] and a personal contribution from A Pidgley, UK National Institute of Health Research (NIHR) University College London Hospitals/UCL Biomedical Research Centres funding scheme.
目前尚无针对继发进展型多发性硬化症（secondary progressive multiple sclerosis）的有效治疗方法，而该疾病约占多发性硬化症患者残疾的大部分。辛伐他汀（simvastatin）作为一种广泛用于治疗血管疾病的药物，具有免疫调节和神经保护作用，因此可能成为继发进展型多发性硬化症患者的一种有吸引力的候选药物。
我们于 2008 年 1 月 28 日至 2011 年 11 月 4 日在英国的三个神经科学中心进行了这项双盲、对照试验。纳入年龄在 18-65 岁之间的患有继发进展型多发性硬化症的患者，按 1:1 的比例，通过中央化的基于网络的服务，按 8 个患者为一组的大小，随机分配接受 80mg 辛伐他汀或安慰剂治疗。患者、治疗医生和结局评估人员对治疗分配情况设盲。主要结局是从连续容积 MRI 测量的全脑萎缩的年增长率。分析按意向治疗和方案进行。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00647348。
140 名参与者被随机分配接受辛伐他汀（n=70）或安慰剂（n=70）治疗。辛伐他汀组患者的年平均萎缩率（0.288%/年[0.521]）显著低于安慰剂组（0.584%/年[0.498]）。两组之间的萎缩率差异为-0.254%/年（95%CI-0.422 至-0.087；p=0.003），即年增长率降低 43%。辛伐他汀耐受性良好，安慰剂组和辛伐他汀组发生严重不良事件的参与者比例无差异（14 名[20%]比 9 名[13%]）。
高剂量辛伐他汀与安慰剂相比降低了全脑萎缩的年增长率，并且具有良好的耐受性和安全性。这些结果支持将该治疗方法推进到 3 期试验。
Moulton 基金会（charity number 1109891）、Berkeley 基金会（268369）、多发性硬化症临床试验协作组（1113598）、Rosetrees 信托基金（298582）和 A Pidgley 的个人捐款，英国国家健康研究所（NIHR）大学学院伦敦医院/UCL 生物医学研究中心资助计划。
