Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease - 01/01/25

Doi : 10.1016/j.tjpad.2024.100022

Sandar Aye ^a,^⁎ , Gunilla Johansson ^a, Christoph Hock ^b, Lars Lannfelt ^c,^d, John R Sims ^e, Kaj Blennow ^f,^g,^h,ⁱ, Kristian S Frederiksen ^j,^k, Caroline Graff ^a,^l, José Luis Molinuevo ^m,ⁿ, Philip Scheltens ^o, Sebastian Palmqvist ^p,^q, Michael Schöll ^r,^s,^t,^u, Anders Wimo ^a, Miia Kivipelto ^v,^w,^x, Ron Handels ^a,^y, Lutz Frölich ^z, Norbert Zilka ^aa, Martin Tolar ^bb, Peter Johannsen ^cc, Linus Jönsson ^a, Bengt Winblad ^a,^dd
^a Division of Neurogeriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, BioClinicum, 171 64 Solna, Sweden
^b Neurimmune, 8952 Zurich-Schlieren, Switzerland
^c Dept. of Public Health, Geriatrics, Uppsala University, Sweden
^d BioArctic AB, Stockholm, Sweden
^e Eli Lilly and Company, Indianapolis, IN, USA
^f Inst. of Neuroscience and Physiology, University of Gothenburg, Mölndal, Sweden
^g Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden
^h Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France
ⁱ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei, PR China
^j Danish Dementia Research Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
^k Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
^l Theme Inflammation and Aging, Unit for hereditary dementias Karolinska University Hospital Solna, Sweden
^m Global Clinical Development, H. Lundbeck A/S, 2500 Valby, Denmark
ⁿ BarcelonaBeta Brain Research Center, 08005 Barcelona, Spain
^o EQT Group, Dementia Fund, Amsterdam, the Netherlands
^p Clinical Memory Research Unit, Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden
^q Memory Clinic, Skåne University Hospital, Sweden
^r Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
^s Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden
^t Department of Psychiatry, Cognition and Aging Psychiatry, Sahlgrenska University Hospital, Mölndal, Sweden
^u Dementia Research Centre, Institute of Neurology, University College London, London, UK
^v Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Theme Inflammation and Aging, Karolinska University Hospital, Stockholm, Sweden
^w Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland
^x The Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, United Kingdom
^y Department of Psychiatry and Neuropsychology, Maastricht University, Alzheimer Centre Limburg, Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, 6200 MD, Maastricht, the Netherlands
^z Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany
^aa Axon Neuroscience R&D Services SE, Dvorakovo nabrezie 10, 811 02 Bratislava, Slovakia
^bb Alzheon, Inc., 111 Speen Street, Framingham, MA, USA
^cc Medical & Science, Clinical Drug Development. Novo Nordisk A/S, DK-2860 Soeborg, Denmark
^dd Theme Inflammation and Aging, Karolinska University Hospital, 141 86 Stockholm, Sweden

^⁎Corresponding author.

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Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 01 January 2025

Abstract

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well as cost-effectiveness and reimbursement issues.

This article brings together insights from a diverse group of international researchers and dementia experts and outlines the potential challenges and opportunities, urging all stakeholders to prepare for the introduction of DMTs. We emphasize the need to develop appropriate use criteria, including patient characteristics, specifically for the European healthcare system, to ensure that treatments are administered to the most suitable patients. It is crucial to improve the skills and knowledge of physicians to accurately interpret biomarker results, share decision-making with patients, recognize treatment-related side effects, and monitor long-term treatment. We advocate for investment in patient registries and unbiased follow-up studies to better understand treatment effectiveness, evaluate treatment-related side effects, and optimize long-term treatment. Utilizing amyloid-targeting therapies as a starting point for combination therapies should also be a priority.

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Keywords : Alzheimer's disease, Disease-modifying treatments, Amyloid-targeting therapies, Challenges in clinical implementation