APOE ε4's impact on response to amyloid therapies in early symptomatic Alzheimer's disease: Analyses from multiple clinical trials.

Autor:	Evans CD; Eli Lilly and Company, Indianapolis, Indiana, USA., Sparks J; Eli Lilly and Company, Indianapolis, Indiana, USA., Andersen SW; Eli Lilly and Company, Indianapolis, Indiana, USA., Brooks DA; Eli Lilly and Company, Indianapolis, Indiana, USA., Hauck PM; Eli Lilly and Company, Indianapolis, Indiana, USA., Mintun MA; Eli Lilly and Company, Indianapolis, Indiana, USA.; Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, Philadelphia, Pennsylvania, USA., Sims JR; Eli Lilly and Company, Indianapolis, Indiana, USA.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Dec; Vol. 19 (12), pp. 5407-5417. Date of Electronic Publication: 2023 May 19.
DOI:	10.1002/alz.13128
Abstrakt:	Introduction: Apolipoprotein E (APOE) ε4 may interact with response to amyloid-targeting therapies. Methods: Aggregate data from trials enrolling participants with amyloid-positive, early symptomatic Alzheimer's disease (AD) were analyzed for disease progression. Results: Pooled analysis of potentially efficacious antibodies lecanemab, aducanumab, solanezumab, and donanemab shows slightly better efficacy in APOE ε4 carriers than in non-carriers. Carrier and non-carrier mean (95% confidence interval) differences from placebo using Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) were -0.30 (-0.478, -0.106) and -0.20 (-0.435, 0.042) and AD Assessment Scale-Cognitive subscale (ADAS-Cog) values were -1.01 (-1.577, -0.456) and -0.80 (-1.627, 0.018), respectively. Decline in the APOE ε4 non-carrier placebo group was equal to or greater than that in carriers across multiple scales. Probability of study success increases as the representation of the carrier population increases. Discussion: We hypothesize that APOE ε4 carriers have same or better response than non-carriers to amyloid-targeting therapies and similar or less disease progression with placebo in amyloid-positive trials. Highlights: Amyloid-targeting therapies had slightly greater efficacy in apolipoprotein E (APOE) ε4 carriers. Clinical decline is the same/slightly faster in amyloid-positive APOE ε4 non-carriers. Prevalence of non-carriers in trial populations could impact outcomes. (© 2023 Eli Lilly and Company. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
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