Journal of neurology, neurosurgery, and psychiatry · 2020
Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis.
СтатьяМетаанализПоддержка исследования: вне правительства СШАСистематический обзорНазвание и аннотация: Перевод в очереди
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Lu Liming, Zheng Xiaoyan, Wang Shengwen, Tang Chunzhi, Zhang Yuqing, Yao Gaolei, Zeng Jingchun, Ge Shuqi, Wen Hao, Xu Mingzhu, Guyatt Gordon, Xu Nenggui
Аннотация
OBJECTIVE: To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer's disease.
METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.
RESULTS: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.
DISCUSSION: From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.
TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42019126272.
METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.
RESULTS: Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer's Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI -0.40 to 0.81; I 2=99.8%; minimal important difference 3.1-3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: -0.96, 95% CI -0.99 to -0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.
DISCUSSION: From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.
TRIAL REGISTRATION NUMBER: PROSPERO registration number CRD42019126272.
Предметные рубрики MeSH
AcitretinAlanineAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedAnxietyAzepinesClioquinolCopperCyclic S-OxidesDepressionDiarrheaExanthemaFatigueFlurbiprofenHumansImmunoglobulins, IntravenousInositolMental Status and Dementia TestsMinimal Clinically Important DifferenceOrotic AcidOxadiazolesSeverity of Illness IndexSulfonamidesSyncopeThiadiazinesTreatment OutcomeVomiting