INSERM, U1137, CIC-EC 1425, Department of Epidemiology, Biostatistics, and Clinical Research, AP-HP, Hospital Bichat, University Paris Diderot Paris, Paris, France.
Department of Neurology, University Hospital of Heidelberg, Heidelberg, Germany.
J Neurol. 2021 Aug;268(8):2749-2756. doi: 10.1007/s00415-020-09815-2. Epub 2020 Apr 7.
Spinocerebellar ataxias (SCAs) are rare dominantly inherited neurodegenerative disorders that lead to severe disability and premature death.
To better characterize the natural history of the most common SCAs, SCA1, SCA2, SCA3 and SCA6, we performed a meta-analysis of literature to determine disease progression, provide data for sample-sizes calculations for interventional trials and study the impact of geographical locations and study follow-up on disease progression.
A systematic literature search from MEDLINE and EMBASE databases for longitudinal natural history studies of SCA patients was conducted. Studies using the Scale for the Assessment and Rating Ataxia (SARA) as outcome measure were considered. Random-effect (RE) meta-analysis was applied to estimate pooled disease progression.
Six studies with 1215 SCA patients enrolled between 2005 and 2016 were finally selected. Annual pooled SARA score increase was 1.83 (1.46-2.20) in patients with SCA1, 1.40 (1.19-1.61) in patients with SCA2, 1.41 (0.97-1.84) in patients with SCA3, and 0.81 (0.66-0.97) in patients with SCA6. For patients with SCA3, disease progression was faster in studies located in Asia and Europe than in the US. Two-arm interventional trials of 1-year duration to achieve 80% power and α level of 5% would require 92 patients per group with SCA1, 97 with SCA2, 115 with SCA3, and 430 with SCA6 to detect a 50% reduction in disease progression.
This meta-analysis provides quantitative data on the progression of the most common spinocerebellar ataxias based on patient numbers that exceed those of previous studies and confirms that disease progression is faster in SCA1, intermediate in SCA2 and SCA3 and slower in SCA6, with similar rates of disease progression in SCA2 and SCA3 between different populations, suggesting a possibility of international collaborative studies. Nevertheless, individual-patient data meta-analysis is needed to better understand the risk factors that influence disease progression and improve patient stratification in interventional trials.
脊髓小脑共济失调（SCA）是一种罕见的显性遗传性神经退行性疾病，可导致严重残疾和过早死亡。
为了更好地描述最常见的 SCA（SCA1、SCA2、SCA3 和 SCA6）的自然病史，我们对文献进行了荟萃分析，以确定疾病进展情况，为干预试验的样本量计算提供数据，并研究地理位置和研究随访对疾病进展的影响。
对 MEDLINE 和 EMBASE 数据库进行了系统性文献检索，以寻找 SCA 患者的纵向自然病史研究。考虑使用共济失调评定量表（SARA）作为结局指标的研究。应用随机效应（RE）荟萃分析来估计汇总的疾病进展情况。
最终选择了 6 项研究，共纳入了 2005 年至 2016 年期间的 1215 名 SCA 患者。SCA1 患者的年度汇总 SARA 评分增加为 1.83（1.46-2.20），SCA2 患者为 1.40（1.19-1.61），SCA3 患者为 1.41（0.97-1.84），SCA6 患者为 0.81（0.66-0.97）。对于 SCA3 患者，来自亚洲和欧洲的研究中疾病进展速度快于来自美国的研究。对于为期 1 年、达到 80%功效和 5%α水平的两臂干预性试验，SCA1 需要每组 92 例患者，SCA2 需要每组 97 例患者，SCA3 需要每组 115 例患者，SCA6 需要每组 430 例患者，才能检测到疾病进展减少 50%。
本荟萃分析基于超过以往研究的患者数量，提供了最常见脊髓小脑共济失调的进展情况的定量数据，并证实 SCA1 中的疾病进展较快，SCA2 和 SCA3 中的疾病进展中等，SCA6 中的疾病进展较慢，不同人群中 SCA2 和 SCA3 之间的疾病进展速度相似，提示有可能开展国际合作研究。然而，需要进行个体患者数据的荟萃分析，以更好地了解影响疾病进展的危险因素，并改善干预试验中的患者分层。
