共济失调-毛细血管扩张症神经系统表现的药物干预：随机对照试验的最新系统评价与Meta分析。
完整摘要 · 中文译文
共济失调-毛细血管扩张症（A-T）会导致进行性神经功能障碍。在2026年发表的两项III期试验之后，本研究针对A-T神经表现的药物干预提供了更新的随机证据。检索了PubMed/MEDLINE、Scopus、Web of Science核心合集和Cochrane图书馆。纳入研究为A-T儿童或成人中的随机对照试验（RCT）。使用Cochrane RoB 2评估偏倚风险。N-乙酰-L-亮氨酸/左乙酰亮氨酸对SARA的治疗效应采用随机效应通用逆方差模型合并，使用限制性最大似然法（REML），并进行共同效应和Hartung-Knapp-Sidik-Jonkman敏感性分析。二次分析合并了两项eDSP试验的完整ICARS疗效和安全性结局。六项RCT评估了口服倍他米松、N-乙酰-L-亮氨酸/左乙酰亮氨酸、红细胞包裹的地塞米松磷酸钠（eDSP）和三庚酸甘油酯。两项交叉试验纳入SARA荟萃分析。合并的REML效应不显著（MD -0.90，95% CI -3.20至1.40；p = 0.443；I²=75.8%）。两项eDSP试验在6-9岁儿童中提供了可比较的完整ICARS估计值；常规合并结果支持eDSP（MD -4.03，95% CI -6.78至-1.29）。两项eDSP试验均未达到其预设的主要神经学终点。合并的eDSP风险比为：任何治疗中出现的不良事件1.05（0.94至1.17），治疗相关事件1.45（0.995至2.12），严重不良事件0.94（0.40至2.22）。倍他米松和三庚酸甘油酯各由一项RCT代表。尽管 FDA批准左乙酰亮氨酸用于治疗A-T中的共济失调，但汇总的SARA效应仍不一致。有利的次要eDSP full-ICARS估计值不能取代未获成功的 primary trial analyses。需要统一、可行的神经学结局指标。PROSPERO注册号CRD420261474940。
完整摘要 · 英文原文
Ataxia-telangiectasia (A-T) causes progressive neurological disability. Following two phase III trials published in 2026, this study is an updated randomized evidence for pharmacological interventions targeting neurological manifestations of A-T. PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Cochrane Library were searched. Eligible studies were RCTs in children or adults with A-T. Risk of bias was assessed using Cochrane RoB 2. N-acetyl-L-leucine/levacetylleucine SARA treatment effects were pooled using a random-effects generic inverse-variance model with restricted maximum likelihood (REML), with common-effect and Hartung-Knapp-Sidik-Jonkman sensitivity analyses. Secondary analyses pooled full-ICARS efficacy and safety outcomes from the two eDSP trials. Six RCTs evaluated oral betamethasone, N-acetyl-L-leucine/levacetylleucine, erythrocyte-encapsulated dexamethasone sodium phosphate (eDSP), and triheptanoin. Two crossover trials contributed to the SARA meta-analysis. The pooled REML effect was not significant (MD -0.90, 95% CI -3.20 to 1.40; p = 0.443; I²=75.8%). Two eDSP trials contributed comparable full-ICARS estimates in children aged 6-9 years; the conventional pooled result favored eDSP (MD -4.03, 95% CI -6.78 to -1.29). Neither eDSP trial met its prespecified primary neurological endpoint. Pooled eDSP risk ratios were 1.05 (0.94 to 1.17) for any treatment-emergent adverse event, 1.45 (0.995 to 2.12) for treatment-related events, and 0.94 (0.40 to 2.22) for serious adverse events. Betamethasone and triheptanoin were each represented by one RCT. Despite FDA approval of levacetylleucine for ataxia in A-T, pooled SARA effects remain inconsistent. The favorable secondary eDSP full-ICARS estimate does not supersede the unsuccessful primary trial analyses. Harmonized, feasible neurological outcome measures are needed.PROSPERO Registration NumberCRD420261474940.