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A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial

INTRODUCTION: Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and one of the leading causes of death for elderly people in the USA. Lecanemab is a humanized IgG1 monoclonal antibody targeting amyloid protofibrils for the treatment of early AD [i.e., m...

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Autores principales: Tahami Monfared, Amir Abbas, Ye, Weicheng, Sardesai, Aditya, Folse, Henri, Chavan, Ameya, Aruffo, Elena, Zhang, Quanwu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195966/
https://www.ncbi.nlm.nih.gov/pubmed/37009976
http://dx.doi.org/10.1007/s40120-023-00473-w
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author Tahami Monfared, Amir Abbas
Ye, Weicheng
Sardesai, Aditya
Folse, Henri
Chavan, Ameya
Aruffo, Elena
Zhang, Quanwu
author_facet Tahami Monfared, Amir Abbas
Ye, Weicheng
Sardesai, Aditya
Folse, Henri
Chavan, Ameya
Aruffo, Elena
Zhang, Quanwu
author_sort Tahami Monfared, Amir Abbas
collection PubMed
description INTRODUCTION: Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and one of the leading causes of death for elderly people in the USA. Lecanemab is a humanized IgG1 monoclonal antibody targeting amyloid protofibrils for the treatment of early AD [i.e., mild cognitive impairment (MCI) or mild AD dementia]. In a recent 18-month phase III trial, using a double-blind, placebo-controlled design, lecanemab treatment led to reduced brain amyloid burden and significant improvements in cognitive and functional abilities in individuals with early AD. METHODS: An evidence-based patient-level disease simulation model was updated to estimate the long-term health outcomes of lecanemab plus standard of care (SoC) compared to SoC alone in patients with early AD and evidence of brain amyloid burden, using recent phase III trial data and published literature. The disease progression is described by changes in the underlying biomarkers of AD, including measures of amyloid and tau, and their connection to the clinical presentation of the disease assessed through various patient-level scales of cognition and function. RESULTS: Lecanemab treatment was estimated to slow the progression of AD to moderate and severe stages and reduce the time spent in these more advanced states. In individuals with early AD, lecanemab plus SoC was associated with a gain of 0.71 quality-adjusted life-years (QALYs), a 2.95-year delay in mean time to progression to AD dementia, a reduction of 0.11 years in institutional care, and an additional 1.07 years in community care as shown in the base-case study. Improved health outcomes were demonstrated with lecanemab treatment when initiated earlier based on age, disease severity, or tau pathology, resulting in estimated gains in QALYs ranging from 0.77 to 1.09 years, compared to 0.4 years in the mild AD dementia subset, as shown by the model. CONCLUSION: The study findings demonstrate the potential clinical value of lecanemab for individuals with early AD by slowing down disease progression and prolonging time in earlier stages of disease, which significantly benefits not only patients and caregivers but also society overall. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03887455. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00473-w.
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spelling pubmed-101959662023-05-20 A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial Tahami Monfared, Amir Abbas Ye, Weicheng Sardesai, Aditya Folse, Henri Chavan, Ameya Aruffo, Elena Zhang, Quanwu Neurol Ther Original Research INTRODUCTION: Alzheimer’s disease (AD), a progressive neurodegenerative disease, is the main cause of dementia and one of the leading causes of death for elderly people in the USA. Lecanemab is a humanized IgG1 monoclonal antibody targeting amyloid protofibrils for the treatment of early AD [i.e., mild cognitive impairment (MCI) or mild AD dementia]. In a recent 18-month phase III trial, using a double-blind, placebo-controlled design, lecanemab treatment led to reduced brain amyloid burden and significant improvements in cognitive and functional abilities in individuals with early AD. METHODS: An evidence-based patient-level disease simulation model was updated to estimate the long-term health outcomes of lecanemab plus standard of care (SoC) compared to SoC alone in patients with early AD and evidence of brain amyloid burden, using recent phase III trial data and published literature. The disease progression is described by changes in the underlying biomarkers of AD, including measures of amyloid and tau, and their connection to the clinical presentation of the disease assessed through various patient-level scales of cognition and function. RESULTS: Lecanemab treatment was estimated to slow the progression of AD to moderate and severe stages and reduce the time spent in these more advanced states. In individuals with early AD, lecanemab plus SoC was associated with a gain of 0.71 quality-adjusted life-years (QALYs), a 2.95-year delay in mean time to progression to AD dementia, a reduction of 0.11 years in institutional care, and an additional 1.07 years in community care as shown in the base-case study. Improved health outcomes were demonstrated with lecanemab treatment when initiated earlier based on age, disease severity, or tau pathology, resulting in estimated gains in QALYs ranging from 0.77 to 1.09 years, compared to 0.4 years in the mild AD dementia subset, as shown by the model. CONCLUSION: The study findings demonstrate the potential clinical value of lecanemab for individuals with early AD by slowing down disease progression and prolonging time in earlier stages of disease, which significantly benefits not only patients and caregivers but also society overall. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03887455. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40120-023-00473-w. Springer Healthcare 2023-04-02 /pmc/articles/PMC10195966/ /pubmed/37009976 http://dx.doi.org/10.1007/s40120-023-00473-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Original Research
Tahami Monfared, Amir Abbas
Ye, Weicheng
Sardesai, Aditya
Folse, Henri
Chavan, Ameya
Aruffo, Elena
Zhang, Quanwu
A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title_full A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title_fullStr A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title_full_unstemmed A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title_short A Path to Improved Alzheimer’s Care: Simulating Long-Term Health Outcomes of Lecanemab in Early Alzheimer’s Disease from the CLARITY AD Trial
title_sort path to improved alzheimer’s care: simulating long-term health outcomes of lecanemab in early alzheimer’s disease from the clarity ad trial
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195966/
https://www.ncbi.nlm.nih.gov/pubmed/37009976
http://dx.doi.org/10.1007/s40120-023-00473-w
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