Huang Xinyue, Sun Chong, Chen Haofeng, Zhao Chongbo, Lin Jie
Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Ther Adv Neurol Disord. 2024 Sep 12;17:17562864241273079. doi: 10.1177/17562864241273079. eCollection 2024.
Hereditary transthyretin amyloidosis (ATTRv; v for variant) with polyneuropathy is a rare, progressive, and fatal autosomal dominant disorder. Therapies such as liver transplantation and TTR stabilizations have limitations. Patisiran is a small interfering RNA (siRNA), offering potential as a genetic-level therapy for hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, evidence on patisiran's efficacy and safety for ATTRv-PN remains limited.
This study aimed to further clarify patisiran's efficacy and safety for ATTRv-PN by meta-analysis.
Systematic review and meta-analysis.
After literature searches in PubMed, Ovid MEDLINE, Embase, JBI EBP, Cochrane, and ClinicalTrials.gov databases on 7 June 2024, 11 studies with 503 patients were included and clinical data were extracted.
Results showed an 88% (95% confidence interval (CI): 81%-94%) pooled responsiveness rate. The standardized mean difference of modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) scores was -0.18 (95% CI: -0.32 to -0.03, -value 0.018) and Norfolk Quality of Life-Diabetic Neuropathy was -0.21 (95% CI: -0.35 to -0.08, -value 0.002). In total, 413 adverse events (AEs) (84.8%), 158 serious AEs (32.4%), and 37 deaths (7.6%) were recorded. Most of AEs were mild to moderate. No deaths were attributed to patisiran. However, there is no statistically significant improvement in Neuropathy Impairment Scores.
In conclusion, patisiran was effective and safe for patients with ATTRv-PN. More large-scale clinical trials and long-term studies are necessary to further validate patisiran's efficacy and safety.
PROSPERO registration ID: CRD42023428838.
遗传性转甲状腺素蛋白淀粉样变性（ATTRv；v代表变异型）伴多发性神经病是一种罕见的、进行性的、致命的常染色体显性疾病。肝移植和转甲状腺素蛋白（TTR）稳定化等治疗方法存在局限性。帕替拉韦是一种小干扰RNA（siRNA），有望成为遗传性转甲状腺素蛋白淀粉样变性伴多发性神经病（ATTRv-PN）的基因水平治疗方法。然而，关于帕替拉韦对ATTRv-PN疗效和安全性的证据仍然有限。
本研究旨在通过荟萃分析进一步阐明帕替拉韦对ATTRv-PN的疗效和安全性。
系统评价和荟萃分析。
于2024年6月7日在PubMed、Ovid MEDLINE、Embase、JBI EBP、Cochrane和ClinicalTrials.gov数据库中进行文献检索，纳入11项研究共503例患者，并提取临床数据。
结果显示汇总反应率为88%（95%置信区间（CI）：81%-94%）。改良神经病损害评分加7项神经测试（mNIS + 7）评分的标准化平均差为-0.18（95%CI：-0.32至-0.03，P值0.018），诺福克糖尿病性神经病生活质量评分为-0.21（95%CI：-0.35至-0.08，P值0.002）。共记录413例不良事件（AE）（84.8%）、158例严重AE（32.4%）和37例死亡（7.6%）。大多数AE为轻至中度。没有死亡归因于帕替拉韦。然而，神经病损害评分没有统计学上的显著改善。
总之，帕替拉韦对ATTRv-PN患者有效且安全。需要更多大规模临床试验和长期研究来进一步验证帕替拉韦的疗效和安全性。
PROSPERO注册号：CRD42023428838。
