Objectives: To estimate the effect of riluzole on the stage-specific risk of progression of ALS. Methods: Patients from the PRO-ACT dataset were staged employing two methods (King's and FT9). Hazard ratios associated with riluzole treatment were estimated for forward transition between stages, using unadjusted and adjusted Markov multistate models. Results: Of 1903 patients, 1587 had received riluzole. Riluzole-treated patients survived non-significantly longer than those who did not (median 22.9 months vs. 18.3 months from time of initial observation, log rank p = 0.16). After adjusting for age and ALSFRS-R slope at first visit, riluzole significantly reduced risk of the following transitions: (1) King's stages: 1->2 (hazard ratio (HR) = 0.81), and 2->3 (HR = 0.82), 4->death (HR = 0.57), and (2) FT9 stages: 1->2 (HR = 0.84), 3->4 (HR = 0.71), and 4->death (HR = 0.67). In contrast, the beneficial effect of riluzole in bulbar-onset patients was in early rather than late King's stages. Conclusions: This examination of cohorts closely followed in clinical trials finds a beneficial effect of riluzole that is predominantly but not exclusively in later stages of ALS. This analytic framework has utility to discern stage-specific treatment effects, and for refined health economic analyses.

中文翻译：

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肌萎缩性侧索硬化的特定阶段利鲁唑效应：一项回顾性研究。

目的：评估利鲁唑对ALS进展特定阶段风险的影响。方法：采用两种方法（King's和FT9）对来自PRO-ACT数据集的患者进行分期。使用未经调整和调整后的马尔可夫多状态模型估算了利鲁唑治疗相关的危险比，以评估各阶段之间的正向过渡。结果：在1903名患者中，有1587名接受了利鲁唑治疗。利鲁唑治疗的患者比未存活的患者无显着延长生存时间（中位观察时间为22.9个月，而初次观察时为18.3个月，对数等级p = 0.16）。在首次就诊时调整年龄和ALSFRS-R斜率后，利鲁唑显着降低了以下转变的风险：（1）国王时期：1-> 2（危险比（HR）= 0.81）和2-> 3（HR = 0.82），4->死亡（HR = 0.57）和（2）FT9阶段：1-> 2（HR = 0.84），3-> 4（HR = 0.71）和4->死亡（HR = 0.67）。相比之下，利鲁唑对延髓发作患者的有益作用是早期而不是晚期金氏分期。结论：在临床试验中密切跟踪的队列研究发现，利鲁唑的有益作用主要但并非仅在ALS的后期阶段有效。该分析框架可用于辨别特定阶段的治疗效果，并用于完善的健康经济分析。