OBJECTIVES: Mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) is the earliest symptomatic stage of AD. For therapies in development for MCI due to AD (MCI-AD), delaying progression to later AD stages is a major driver of lifetime clinical and economic value. An evidence-based modeling approach was developed to predict delays in AD dementia for patients treated with a therapy acting on beta-amyloid for MCI-AD.
METHODS: A Markov-based cohort model with annual cycles and a lifetime horizon was developed with health states for MCI-AD, mild AD, moderate AD, severe AD, and death. Natural history progression from MCI-AD to AD dementia for amyloid-positive patients was estimated from published Alzheimer’s Disease Neuroimaging Initiative data. Natural history AD dementia progression, institutionalization, and mortality data were obtained from literature sources. Patients with MCI-AD were treated until they reached moderate AD or worse with a hypothetical therapy reducing the risk of progression by 22%. AD dementia outcomes included the median time to progression (50% of surviving patients reaching dementia), undiscounted life-years (LYs) with dementia, and the lifetime proportion of patients reaching dementia. Alternative longitudinal natural history data sources were explored in scenario analyses.
RESULTS: For patients with MCI-AD, treatment delayed the median time to AD dementia by 2.0 years compared with no treatment (7.3 vs. 5.3 years). LYs with AD dementia per patient were reduced by 0.5 (3.4 vs. 3.9 LYs), while the proportion progressing to AD dementia before death decreased by 7.5% (59.2% vs. 66.6%).
CONCLUSIONS: A treatment for MCI-AD in amyloid-positive patients has the potential to delay AD dementia by 2.0 years, reducing the number of patients advancing to and LYs spent with AD dementia. These clinical benefits should translate to reduced resource utilization and improved quality of life for patients and caregivers.
