Huang Shi-Le, Shen Yin-Li, Peng Wen-Yan, Ye Kun, Zheng Hui
Department of Acupuncture, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu City, China.
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, No. 1166 Liutai Avenue, Wenjiang District, Chengdu City, 610000, China.
Acta Neurol Belg. 2024 Jun;124(3):895-904. doi: 10.1007/s13760-024-02476-2. Epub 2024 Feb 12.
The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone.
The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach.
The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty.
Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy.
依达拉奉是肌萎缩侧索硬化症（ALS）的推荐治疗药物，其有效性和长期疗效尚未在真实世界环境中得到检验。本研究旨在评估依达拉奉的有效性和长期疗效。
检索了OVID Medline、Embase、Cochrane对照试验中央注册库（CENTRAL）和Web of Science数据库中2000年1月1日至2023年5月1日发表的文章。两名研究者独立筛选检索到的文章，寻找评估依达拉奉对肌萎缩侧索硬化症（ALS）疗效的随机对照试验（RCT）、队列研究或单臂试验。使用修订后的Cochrane偏倚风险（RoB 2.0）工具评估随机对照试验（RCT）的偏倚风险，使用干预性非随机研究中的偏倚风险（ROBINS-I）工具评估观察性研究的偏倚风险。主要结局是在第6个月评估的ALSFRS-R评分，次要结局包括在第9、12和18个月评估的ALSFRS-R评分、用力肺活量（FVC）和不良事件。使用GRADE方法评估证据的确定性。
分析纳入了16项研究，共4828名参与者。其中，4项为随机对照试验（RCT），12项为观察性研究。在RCT中，4项被评为偏倚风险低，而在观察性研究中，6项被评为偏倚风险低。RCT的证据表明，与安慰剂相比，依达拉奉在第6个月时ALSFRS-R评分降低的进展略慢（平均差异1.01，95%CI -0.87至3.09，p = 0.293）。然而，观察性研究未显示在常规治疗中添加依达拉奉有任何益处（平均差异1.85，95%CI -2.05至5.75，p = 0.352）。在第3、6、9、12和18个月时，ALSFRS-R评分相对于基线的变化分别为-2.1、-4.04、-7.5、-6.82和-7.9。GRADE评估表明，RCT证据的确定性为中等，而观察性研究的证据确定性非常低。
由于研究数量有限以及观察性研究中存在混杂问题，有必要通过RCT进一步检验依达拉奉在常规治疗中的额外益处，特别是其长期疗效。
