Miller R G, Mitchell J D, Moore D H
Department of Neurology, California Pacific Medical Center, 2324 Sacramento Street, San Francisco, USA, 94115.
Cochrane Database Syst Rev. 2000(2):CD001447. doi: 10.1002/14651858.CD001447.
Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis (ALS) in some countries but not others. Questions persist about its clinical utility because of high cost, modest efficacy and concern over adverse effects.
To examine the efficacy of riluzole in prolonging survival, and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival.
Search of the Cochrane Neuromuscular Disease Group Register for randomized trials and enquiry from authors of trials and other experts in the field. The most recent search was conducted in June 1999.
Types of studies: randomized trials
adults with a diagnosis of ALS Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: per cent mortality at 12 months with riluzole 100 mg Secondary: per cent mortality as a function of time with 100 mg and with all doses of riluzole, scales of neurologic function, quality of life, muscle strength and adverse events.
We identified two randomized trials. Each reviewer graded them for methodological quality. Data extraction was performed by a single reviewer and checked by the other two. We obtained some missing data from investigators. We performed meta-analyses with RevMan software using a fixed effects model.
The two eligible trials included a total of 794 riluzole treated patients and 320 placebo treated patients. The methodological quality was acceptable and the trials were easily comparable. There were significant differences between the riluzole and placebo groups of both trials, in terms of the primary outcome measure, which was per cent mortality at 12 months with the 100 mg dose of riluzole. The odds ratio for the combined studies was 0.57 (95%CI 0.41 to 0.80) at 12 months. In the secondary outcome measures, there was a survival advantage with riluzole 100 mg at six, nine, 12 and 15 months, but not at three or 18 months. Pooled data from the 50, 100 and 200mg dose groups in the larger trial showed a lower per cent mortality with riluzole compared to placebo only at 12 months (odds ratio (OR) 0.64, 95% CI 0.47 to 0.88). There was no beneficial effect on bulbar function, or muscle strength. There were scant data on quality of life, but patients treated with riluzole remained in a more moderately affected health state significantly longer than placebo-treated patients (weighted mean difference (WMD) 35.5 days, 95% CI 5.9 to 65. 0). A threefold increase in serum alanine transferase was more frequent in riluzole treated patients than controls (WMD 2.65, 95% CI 1.51 to 4.65).
REVIEWER'S CONCLUSIONS: Riluzole 100 mg per day appears to be modestly effective in prolonging survival for patients with ALS.
利鲁唑在一些国家已被批准用于治疗肌萎缩侧索硬化症（ALS）患者，但在其他国家尚未获批。由于成本高昂、疗效一般以及对不良反应的担忧，其临床实用性仍存在疑问。
研究利鲁唑在延长生存期以及推迟使用替代手段（气管切开术和机械通气）维持生命方面的疗效。
检索Cochrane神经肌肉疾病组注册库中的随机试验，并向试验作者及该领域的其他专家咨询。最近一次检索于1999年6月进行。
研究类型：随机试验；参与者类型：诊断为ALS的成年人；干预措施类型：使用利鲁唑或安慰剂治疗；结局指标类型：主要指标：服用100mg利鲁唑的患者12个月时的死亡率百分比；次要指标：服用100mg利鲁唑及所有剂量利鲁唑的患者随时间变化的死亡率百分比、神经功能量表、生活质量、肌肉力量及不良事件。
我们确定了两项随机试验。每位评审员对其方法学质量进行评分。数据提取由一名评审员进行，另外两名评审员进行核对。我们从研究者处获取了一些缺失数据。我们使用RevMan软件采用固定效应模型进行荟萃分析。
两项符合条件的试验共纳入794例接受利鲁唑治疗的患者和320例接受安慰剂治疗的患者。方法学质量可接受，试验易于比较。在两项试验的利鲁唑组和安慰剂组之间，就主要结局指标而言，即服用100mg利鲁唑的患者12个月时的死亡率百分比，存在显著差异。联合研究在12个月时的比值比为0.57（95%可信区间0.41至0.80）。在次要结局指标中，服用100mg利鲁唑在6个月、9个月、12个月和15个月时有生存优势，但在3个月或18个月时没有。较大试验中50mg、100mg和200mg剂量组的汇总数据显示，仅在12个月时，与安慰剂相比，利鲁唑治疗组的死亡率百分比更低（比值比（OR）0.64，95%可信区间0.47至0.88）。对延髓功能或肌肉力量没有有益影响。关于生活质量的数据很少，但接受利鲁唑治疗的患者保持病情中度受影响状态的时间明显长于接受安慰剂治疗的患者（加权平均差（WMD）35.5天，95%可信区间5.9至65.0）。接受利鲁唑治疗的患者血清丙氨酸转氨酶升高三倍的情况比对照组更常见（加权平均差2.65，95%可信区间1.51至4.65）。
每天服用100mg利鲁唑似乎对延长ALS患者的生存期有一定疗效。
