TY - JOUR
T1 - Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer’s Disease
AU - Herring, William L.
AU - Gould, Ian Gopal
AU - Fillit, Howard
AU - Lindgren, Peter
AU - Forrestal, Fiona
AU - Thompson, Robin
AU - Pemberton-Ross, Peter
N1 - Funding Information:
William L. Herring is an employee of RTI Health Solutions (RTI-HS), an independent nonprofit research organization. Ian Gopal Gould was an employee of RTI-HS at the time this study was conducted. RTI-HS received funding for this study under a research contract with Biogen International GmbH (Biogen). Howard Fillit has received fees from Biogen for educational programs, and consulting fees from Samus Therapeutics, Otsuka, and Alector. Peter Lindgren reports advisory boards, speaking assignments and research grants from: Amgen, Astellas, AstraZeneca, BioMarin, European Federation of Pharmaceutical Industries and Associations, Merck Sharp & Dohme, Novartis, NovoNordisk, and Takeda. Fiona Forrestal, Robin Thompson, and Peter Pemberton-Ross are employees and shareholders of Biogen.
Funding Information:
This study and the journal’s Rapid Service Fee was funded by Biogen (Cambridge, MA, USA).
Funding Information:
Medical writing support, under the direction of the authors, was provided by Rosalind Carney, DPhil, of MediTech Media Ltd, and funded by Biogen (Cambridge, MA, USA).
Funding Information:
This study and the journal’s Rapid Service Fee was funded by Biogen (Cambridge, MA, USA). Medical writing support, under the direction of the authors, was provided by Rosalind Carney, DPhil, of MediTech Media Ltd, and funded by Biogen (Cambridge, MA, USA). All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. WLH, IGG, RT, and PP-R conceptualized the study and study design. WLH and IGG developed the model and performed the analyses with input from RT and PP-R. FF designed and conducted the post-hoc EMERGE efficacy analysis with input from PP-R. All authors made substantial contributions to the interpretation of the data, critically revised the manuscript for intellectual content, approved the final version to be published, and are accountable for all aspects of the work. William L. Herring is an employee of RTI Health Solutions (RTI-HS), an independent nonprofit research organization. Ian Gopal Gould was an employee of RTI-HS at the time this study was conducted. RTI-HS received funding for this study under a research contract with Biogen International GmbH (Biogen). Howard Fillit has received fees from Biogen for educational programs, and consulting fees from Samus Therapeutics, Otsuka, and Alector. Peter Lindgren reports advisory boards, speaking assignments and research grants from: Amgen, Astellas, AstraZeneca, BioMarin, European Federation of Pharmaceutical Industries and Associations, Merck Sharp & Dohme, Novartis, NovoNordisk, and Takeda. Fiona Forrestal, Robin Thompson, and Peter Pemberton-Ross are employees and shareholders of Biogen. The EMERGE trial was conducted in accordance with Declaration of Helsinki and the International Conference on Harmonization and Good Clinical Practice guidelines and was approved by ethics committees or institutional review boards at each site. All patients provided written informed consent. An independent data monitoring committee was responsible for monitoring the conduct of the trials, assessing safety routinely, and reviewing futility analysis results. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. All data used for this study are provided in the manuscript. Additional details are available from the corresponding author on request.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Introduction: Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. Methods: We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer’s Coordinating Center analyses, and other published literature. Results: Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC. Conclusion: The model predicted long-term benefits of aducanumab treatment in patients with MCI due to AD and mild AD dementia and their caregivers. The predicted outcomes provide a foundation for healthcare decision-makers and policymakers to understand the potential clinical and socioeconomic value of aducanumab.
AB - Introduction: Alzheimer’s disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. Methods: We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer’s Coordinating Center analyses, and other published literature. Results: Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC. Conclusion: The model predicted long-term benefits of aducanumab treatment in patients with MCI due to AD and mild AD dementia and their caregivers. The predicted outcomes provide a foundation for healthcare decision-makers and policymakers to understand the potential clinical and socioeconomic value of aducanumab.
KW - Aducanumab
KW - Alzheimer’s dementia
KW - Alzheimer’s disease
KW - Amyloid plaques
KW - Disease-modifying therapy
KW - Economic model
KW - Institutionalization
KW - Markov model
KW - Natural history
KW - Progression
UR - http://www.scopus.com/inward/record.url?scp=85113289749&partnerID=8YFLogxK
U2 - 10.1007/s40120-021-00273-0
DO - 10.1007/s40120-021-00273-0
M3 - Article
AN - SCOPUS:85113289749
SN - 2193-8253
VL - 10
SP - 919
EP - 940
JO - Neurology and Therapy
JF - Neurology and Therapy
IS - 2
ER -