Abstract

Objective: To compare the effect of riluzole on median survival in population studies of patients with amyotrophic lateral sclerosis (ALS) with that observed in clinical trials. Methods: Two independent PubMed searches were conducted, to identify population studies that reported median survival for ALS patients who were either treated with riluzole or remained riluzole-free. Results: We identified 14 studies that met the inclusion criteria of reporting median survival and an additional study that reported mean survival of both riluzole and riluzole-free patients. Analysis of the 15 studies found that a majority reported increased survival of riluzole vs. riluzole-free patients. In 8 studies, the median survival for patients treated with riluzole was 6–19 months longer compared with patients not treated with riluzole (p < 0.05). Three additional studies reported a clinically meaningful treatment effect (range 3–5.9 months) but did not meet statistical significance. The remaining 4 studies did not show a meaningful treatment effect between riluzole and riluzole-free groups (<3 months), and differences among the groups were not significant. Also, 5 of the studies used multivariate regression analysis to investigate the level of association between treatment with riluzole and survival; these analyses supported the positive effect of riluzole on survival. Conclusions: A majority of population studies that compared riluzole vs. riluzole-free ALS patients found significant differences in median survival between the two groups, ranging from 6 to 19 months. This is substantially longer than the 2- to 3-month survival benefit observed in the pivotal clinical trials of riluzole.

摘要

目的：比较利鲁唑对肌萎缩侧索硬化 (ALS) 患者群体研究和临床试验中观察到的中位生存期的影响。方法：进行了两次独立的 PubMed 搜索，以确定报告了接受利鲁唑治疗或保持无利鲁唑治疗的 ALS 患者的中位生存期的人群研究。结果：我们确定了 14 项符合报告中位生存期纳入标准的研究，以及一项报告了利鲁唑和无利鲁唑患者平均生存期的额外研究。对 15 项研究的分析发现，大多数报告利鲁唑与不含利鲁唑的患者相比存活率增加。在 8 项研究中，接受利鲁唑治疗的患者的中位生存期比未接受利鲁唑治疗的患者长 6-19 个月（p < 0.05)。另外三项研究报告了具有临床意义的治疗效果（范围 3-5.9 个月），但未达到统计学意义。其余 4 项研究未显示利鲁唑组和无利鲁唑组（<3 个月）之间的有意义的治疗效果，组间差异不显着。此外，其中 5 项研究使用多变量回归分析来研究利鲁唑治疗与生存之间的关联水平；这些分析支持利鲁唑对生存的积极影响。结论：大多数比较利鲁唑与不含利鲁唑的 ALS 患者的人群研究发现，两组之间的中位生存期存在显着差异，范围为 6 至 19 个月。这比利鲁唑的关键临床试验中观察到的 2 至 3 个月的生存获益要长得多。