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

Monfared, Amir Abbas Tahami; Ye, Weicheng; Sardesai, Aditya; Folse, Henri; Chavan, Ameya; Aruffo, Elena; Zhang, Quanwu

doi:10.1007/s40120-023-00473-w

Cited by 19 publications

(8 citation statements)

References 35 publications

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“…In a simulation study seeking to estimate long-term healthcare outcomes, lecanemab potentially can increase time spent in the community, rather than in institutional care settings. 57 Further open-label extension analyses from the manufacturer noted a continued 6-month response with lecanemab beyond the initial 18-month trial period. 58 Despite this, adding medications like lecanemab to formularies is not without need for continual reevaluation of use and cost/benefit.…”

Section: Discussionmentioning

confidence: 99%

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Yoon,

Groff,

Criss

2024

Innov Pharm

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The Food and Drug Administration granted traditional approval of lecanemab for the treatment of Alzheimer’s disease (AD). Lecanemab is a humanized anti-amyloid monoclonal antibody directed towards Aβ protofibrils. Lecanemab is the only drug that targets Aβ soluble protofils and has shown statistical differences in mild AD or mild cognitive impairment. In its landmark phase III trial, lecanemab was shown to slow the progression of clinical decline, and a reduction in amyloid protein accumulation. The difference in mean CDR-SOB score improvement between the treatment and placebo groups was -0.45, of which the clinical significance could be argued. Amyloid burden was also considerably reduced as well, but the true clinical consequence of this reduction remains to be seen. This beneficial impact on daily living is offset by rare but serious side effects including amyloid-related imaging abnormalities (ARIA) causing cerebral edema (ARIA-E) or cerebral microhemorrhages or hemosiderin deposits (ARIA-H). Benefits of therapy must be considered against the risk of cerebral microhemorrhages and edema. Affordability must also be taken into consideration. The current estimated yearly cost for twice monthly lecanemab infusion is $26,500. In addition to the significant cost challenges, the frequent infusions may pose concerns related to access. Additional agents within this class are in the pipelines with possibly increased efficacy or decreased adverse events.

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Section: Discussionmentioning

confidence: 99%

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Yoon,

Groff,

Criss

2024

Innov Pharm

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“…What can be appreciated in most circumstances is the time saved and longer residence in more mild stages of impairment [ 84 , 85 ]. Modeling of the lecanemab outcomes with projection beyond an 18-month trial exposure period suggests delayed time to decline of 2.5 years to mild AD dementia [ 86 ]. Early treatment in the disease progression would provide the most benefit to the patient, demonstrating the importance of better screening and diagnostic tools for AD.…”

Section: Discussionmentioning

confidence: 99%

Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer’s Disease

Cummings,

Osse,

Cammann

et al. 2023

BioDrugs

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Two monoclonal antibodies (mAbs), aducanumab and lecanemab, have received accelerated approval from the US FDA for initiation of treatment in early Alzheimer's disease patients who have proven β-amyloid pathology (Aβ). One of these, lecanemab, has subsequently received full approval and other monoclonal antibodies are poised for positive review and approval. Anti-amyloid mAbs share the feature of producing a marked reduction in total brain Aβ revealed by amyloid positron emission tomography. Trials associated with slowing of cognitive decline have achieved a reduction in measurable plaque Aβ in the range of 15–25 centiloids; trials of agents that did not reach this threshold were not associated with cognitive benefit. mAbs have differences in terms of titration schedules, MRI monitoring schedules for amyloid-related imaging abnormalities (ARIA), and continuing versus interrupted therapy. The approximate 30% slowing of decline observed with mAbs is clinically meaningful in terms of extended cognitive integrity and delay of onset of the more severe dementia phases of Alzheimer’s disease. Approval of these agents initiates a new era in Alzheimer’s disease therapeutics with disease-modifying properties. Further advances are needed, i.e. greater efficacy, improved safety, enhanced convenience, and better understanding of ill-understood observations such as brain volume loss.

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“…Previous work has shown that, on average, 548-730 days (1.5-2 years) is a relatively reasonable observation window for the cognitive decline conversion from MCI to AD 19,20 . Similarly, the observation window for patient survival time after being diagnosed with AD is around 548-1095 days (1.5-3 years) 5,21 .…”

Section: Methodsmentioning

confidence: 99%

An Interpretable Population Graph Network to Identify Rapid Progression of Alzheimer’s Disease Using UK Biobank

Meng,

Inampudi,

Zhang

et al. 2024

Preprint

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Alzheimer's disease (AD) manifests with varying progression rates across individuals, necessitating the understanding of their intricate patterns of cognition decline that could contribute to effective strategies for risk monitoring. In this study, we propose an innovative interpretable population graph network framework for identifying rapid progressors of AD by utilizing patient information from electronic health-related records in the UK Biobank. To achieve this, we first created a patient similarity graph, in which each AD patient is represented as a node; and an edge is established by patient clinical characteristics distance. We used graph neural networks (GNNs) to predict rapid progressors of AD and created a GNN Explainer with SHAP analysis for interpretability. The proposed model demonstrates superior predictive performance over the existing benchmark approaches. We also revealed several clinical features significantly associated with the prediction, which can be used to aid in effective interventions for the progression of AD patients.

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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

Cited by 19 publications

References 35 publications

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer’s Disease

Anti-Amyloid Monoclonal Antibodies for the Treatment of Alzheimer’s Disease

An Interpretable Population Graph Network to Identify Rapid Progression of Alzheimer’s Disease Using UK Biobank

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