Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
APOE ε4's impact on response to amyloid therapies in early symptomatic Alzheimer's disease: Analyses from multiple clinical trials.
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Evans Cynthia D, Sparks JonDavid, Andersen Scott W, Brooks Dawn A, Hauck Paula M, Mintun Mark A, Sims John R
Аннотация
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.
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.