| Title: |
Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease |
| Authors: |
Wang, G; Li, Y; Xiong, C; Benzinger, TLS; Gordon, BA; Hassenstab, J; Aschenbrenner, AJ; McDade, E; Clifford, DB; Libre-Guerra, JJ; Shi, X; Mummery, CJ; van Dyck, CH; Lah, JJ; Honig, LS; Day, G; Ringman, JM; Brooks, WS; Fox, NC; Suzuki, K; Levin, J; Jucker, M; Delmar, P; Bittner, T; Bateman, RJ |
| Source: |
Alzheimer's and Dementia (2024) (In press). |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Dominantly Inherited Alzheimer Network; autosomal dominant Alzheimer's disease; gantenerumab; latent class analysis; solanezumab; surrogate biomarker |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10189432/1/Examining%20amyloid%20reduction%20as%20a%20surrogate%20endpoint%20through%20latent%20class%20analysis.pdf; https://discovery.ucl.ac.uk/id/eprint/10189432/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10189432/1/Examining%20amyloid%20reduction%20as%20a%20surrogate%20endpoint%20through%20latent%20class%20analysis.pdf; https://discovery.ucl.ac.uk/id/eprint/10189432/ |
| Rights: |
open |
| Accession Number: |
edsbas.1AD3FA76 |
| Database: |
BASE |