The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer's disease: a meta-analysis.

Autor:	Jiaxuan Li, Xin Wu, Xin Tan, Shixin Wang, Ruisi Qu, Xiaofeng Wu, Zhouqing Chen, Zhong Wang, Gang Chen
Předmět:	THERAPEUTIC use of monoclonal antibodies COGNITION disorders ONLINE information services MEDICAL databases RELATIVE medical risk ALZHEIMER'S disease META-analysis MEDICAL information storage & retrieval systems SYSTEMATIC reviews AMYLOID beta-protein precursor TREATMENT effectiveness INTRAVENOUS immunoglobulins DESCRIPTIVE statistics MEDLINE DATA analysis software DRUG side effects PATIENT safety CHEMICAL inhibitors EVALUATION
Zdroj:	Frontiers in Aging Neuroscience; 2023, p1-12, 12p
Abstrakt:	Background: This meta-analysis evaluates the efficacy and safety of amyloid-ß (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer's disease (AD). Methods: PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023. Results: We pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aβ drugs and placebo in the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and anti-Aβ drugs were associated with a high risk of adverse events [ADAS-Cog: MDs= -0.08 (-0.32 to 0.15), p = 0.4785; AEs: RR= 1.07 (1.02 to 1.11), p = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADASCog: MDs= -0.55 (-0.89 to 0.21), p = 0.001; CDR-SB: MDs= -0.19 (-0.29 to -0.10), p < 0.0001; MMSE: MDs= 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs= 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs= 0.45 (0.17 to 0.74), p = 0.002], but had acceptable safety profiles in AD patients. γ-secretase inhibitors (GSI) increased cognitive decline in ADAS-Cog, and also in MMSE and ADCS-ADL. BACE-1 inhibitors aggravated cognitive deterioration in the outcome of the Neuropsychiatric Inventory (NPI). GSI and BACE-1 inhibitors caused safety concerns. No evidence indicates active Aβ immunotherapy, MPAC, or tramiprosate have effects on cognitive function and tramiprosate is associated with serious adverse events. Conclusion: Current evidence does not show that anti-Aβ drugs have an effect on cognitive performance in AD patients. However, monoclonal antibodies can delay cognitive decline in AD. Development of other types of anti-Aβ drugs should be cautious. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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