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路易体痴呆的治疗选择:随机对照试验的网状Meta分析

Treatment Options for Dementia with Lewy Bodies: A Network Meta-Analysis of Randomised Control Trials.

作者信息

Tahami Monfared Amir A, Desai Mitesh, Hughes Robert, Lucherini Stefano, Yi Yunni, Perry Richard

机构信息

Eisai Inc., Woodcliff Lake, NJ, USA.

Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.

出版信息

Neurol Ther. 2020 Dec;9(2):521-534. doi: 10.1007/s40120-020-00198-0. Epub 2020 Jun 3.

Abstract

INTRODUCTION

Dementia with Lewy bodies (DLB) is the third most common type of dementia after Alzheimer's disease (AD) and vascular dementia. Treatment is targeted at specific disease manifestations/symptoms. While donepezil is approved for the treatment of DLB in Japan, to date no other treatment has been approved for this indication anywhere in the world. Notwithstanding, many of the medications that are approved for AD are widely used in the treatment of DLB with varying degrees of success. Consequently, clinical evidence is limited, and there is a need to understand the comparative efficacy and safety of currently used therapies for DLB. The aim of this study was to conduct a network meta-analysis (NMA) to evaluate the outcomes of the available treatment options based on currently used trial endpoints.

METHODS

Using data from a previously published systematic review, we conducted an NMA to investigate the efficacy and safety of treatments in patients with DLB. Networks were based on change from baseline of efficacy endpoints (Mini-Mental State Examination; Neuropsychiatric Inventory; Unified Parkinson's Disease Rating Scale) and rate of safety events (overall adverse events [AEs]; discontinuations; discontinuations due to AEs; psychiatric events).

RESULTS

Focused around a common treatment option of placebo, the NMA comprised studies on donepezil, rivastigmine, memantine and quetiapine. Donepezil 3 mg, 5 mg and 10 mg doses were compared against each other and placebo. Overall, donepezil consistently performed better than the alternative treatments when compared to placebo for all efficacy and safety endpoints. However, the small sample size and/or heterogeneity of the studies led to uncertainty, resulting in no statistically significant differences favouring any treatment above another or placebo.

CONCLUSION

Despite the lack of statistical significance, when assessing the efficacy and safety outcomes for each drug in the evidence network, donepezil appeared to have a more favourable overall benefit/risk profile for patients with DLB. Further comparative trials are required to improve understanding of the true difference between existing and potential future treatment options.

摘要

引言

路易体痴呆(DLB)是继阿尔茨海默病(AD)和血管性痴呆之后第三常见的痴呆类型。治疗针对特定的疾病表现/症状。虽然多奈哌齐在日本被批准用于治疗DLB,但迄今为止,世界上其他任何地方都没有针对该适应症的其他治疗方法获得批准。尽管如此,许多被批准用于AD的药物在治疗DLB中被广泛使用,且取得了不同程度的成功。因此,临床证据有限,有必要了解目前用于DLB治疗的疗法的相对疗效和安全性。本研究的目的是进行一项网络荟萃分析(NMA),以根据目前使用的试验终点评估现有治疗选择的结果。

方法

利用先前发表的系统评价中的数据,我们进行了一项NMA,以研究DLB患者治疗的疗效和安全性。网络基于疗效终点(简易精神状态检查表;神经精神科问卷;统一帕金森病评定量表)相对于基线的变化以及安全事件发生率(总体不良事件[AEs];停药;因AEs停药;精神事件)。

结果

围绕安慰剂这一常见治疗选择,NMA纳入了关于多奈哌齐、卡巴拉汀、美金刚和喹硫平的研究。对多奈哌齐3mg、5mg和10mg剂量相互之间以及与安慰剂进行了比较。总体而言,与安慰剂相比,在所有疗效和安全性终点方面,多奈哌齐始终比其他治疗表现更好。然而,研究的小样本量和/或异质性导致了不确定性,因此没有统计学上的显著差异表明任何一种治疗优于另一种治疗或安慰剂。

结论

尽管缺乏统计学显著性,但在评估证据网络中每种药物的疗效和安全性结果时,多奈哌齐似乎对DLB患者具有更有利的总体获益/风险概况。需要进一步的比较试验,以更好地了解现有和未来潜在治疗选择之间的真正差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ab4/7606367/fdc5f5d0a607/40120_2020_198_Fig1_HTML.jpg

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