Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease
© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Alzheimer's & dementia : the journal of the Alzheimer's Association - 20(2024), 4 vom: 02. Apr., Seite 2698-2706 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Guoqiao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.04.2024 Date Revised 26.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/alz.13735 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368905101 |
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| 100 | 1 | |a Wang, Guoqiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 26.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a DISCUSSION: LC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Dominantly Inherited Alzheimer Network | |
| 650 | 4 | |a autosomal dominant Alzheimer's disease | |
| 650 | 4 | |a gantenerumab | |
| 650 | 4 | |a latent class analysis | |
| 650 | 4 | |a solanezumab | |
| 650 | 4 | |a surrogate biomarker | |
| 650 | 7 | |a Amyloid |2 NLM | |
| 650 | 7 | |a Amyloidogenic Proteins |2 NLM | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
| 700 | 1 | |a Li, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Chengjie |e verfasserin |4 aut | |
| 700 | 1 | |a Benzinger, Tammie L S |e verfasserin |4 aut | |
| 700 | 1 | |a Gordon, Brian A |e verfasserin |4 aut | |
| 700 | 1 | |a Hassenstab, Jason |e verfasserin |4 aut | |
| 700 | 1 | |a Aschenbrenner, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a McDade, Eric |e verfasserin |4 aut | |
| 700 | 1 | |a Clifford, David B |e verfasserin |4 aut | |
| 700 | 1 | |a Libre-Guerra, Jorge J |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xinyu |e verfasserin |4 aut | |
| 700 | 1 | |a Mummery, Catherine J |e verfasserin |4 aut | |
| 700 | 1 | |a van Dyck, Christopher H |e verfasserin |4 aut | |
| 700 | 1 | |a Lah, James J |e verfasserin |4 aut | |
| 700 | 1 | |a Honig, Lawrence S |e verfasserin |4 aut | |
| 700 | 1 | |a Day, Gregg |e verfasserin |4 aut | |
| 700 | 1 | |a Ringman, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Brooks, William S |e verfasserin |4 aut | |
| 700 | 1 | |a Fox, Nick C |e verfasserin |4 aut | |
| 700 | 1 | |a Suzuki, Kazushi |e verfasserin |4 aut | |
| 700 | 1 | |a Levin, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Jucker, Mathias |e verfasserin |4 aut | |
| 700 | 1 | |a Delmar, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Bittner, Tobias |e verfasserin |4 aut | |
| 700 | 1 | |a Bateman, Randall J |e verfasserin |4 aut | |
| 700 | 0 | |a DIAN‐TU Study Team |e verfasserin |4 aut | |
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