Abstract
INTRODUCTION
Increasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double-blind phase 3 DIAN-TU-001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.
METHODS
We used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker.
RESULTS
LC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid-no-change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid-reduction class exhibited reductions in the annual decline rates compared to the amyloid-growth class across multiple biomarker, clinical, and cognitive outcomes.
DISCUSSION
LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials.
Highlights
We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker.
Despite similar baseline characteristics, the amyloid-reduction class exhibited remarkably better outcomes compared to the amyloid-growth class across multiple measures.
LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects.
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This post is Copyright: Guoqiao Wang,
Yan Li,
Chengjie Xiong,
Tammie L. S. Benzinger,
Brian A. Gordon,
Jason Hassenstab,
Andrew J. Aschenbrenner,
Eric McDade,
David B. Clifford,
Jorge J. Libre‐Guerra,
Xinyu Shi,
Catherine J. Mummery,
Christopher H. van Dyck,
James J. Lah,
Lawrence S. Honig,
Gregg Day,
John M. Ringman,
William S. Brooks,
Nick C. Fox,
Kazushi Suzuki,
Johannes Levin,
Mathias Jucker,
Paul Delmar,
Tobias Bittner,
Randall J. Bateman,
for the DIAN‐TU Study Team | February 24, 2024