Abstract
INTRODUCTION
Recent clinical trials of amyloid beta (Aβ)-targeting therapies in Alzheimer’s disease (AD) have demonstrated a clinical benefit over 18 months, but their long-term impact on disease trajectory is not yet understood. We propose a framework for evaluating realistic long-term scenarios.
METHODS
Results from recent phase 3 trials of Aβ-targeting antibodies were integrated with an estimate of the long-term patient-level natural history trajectory of the Clinical Dementia Rating-Sum of Boxes (CDR-SB) score to explore realistic long-term efficacy scenarios.
RESULTS
Three distinct long-term efficacy scenarios were examined, ranging from conservative to optimistic. These extrapolations of positive phase 3 trials suggested treatments delayed onset of severe dementia by 0.3 to 0.6 years (conservative), 1.1 to 1.9 years (intermediate), and 2.0 to 4.2 years (optimistic).
DISCUSSION
Our study provides a common language for long-term impact of disease-modifying treatments. Our work calls for studies with longer follow-up and results from early intervention trials to provide a comprehensive assessment of these therapies’ true long-term impact.
Highlights
We present long-term scenarios of the efficacy of AD therapies.
In this framework, scenarios are defined relative to the natural history of AD.
Long-term projections with different levels of optimism can be compared.
It provides a common language for expressing beliefs about long-term efficacy.
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This post is Copyright: Lars Lau Raket,
Jeffrey Cummings,
Alexis Moscoso,
Nicolas Villain,
Michael Schöll | July 29, 2024