Progress in the Treatment of Alzheimer's Disease Is Needed - Position Statement of European Alzheimer's Disease Consortium (EADC) Investigators.

β-amyloid-targeting antibodies represent the first generation of effective causal treatment of Alzheimer's disease (AD) and can be considered historical research milestones. Their effect sizes, side effects, implementation challenges and costs, however, have stimulated debates about their overall value. In this position statement academic clinicians of the European Alzheimer's Disease Consortium (EADC) discuss the critical relevance of introducing these new treatments in clinical care now. Given the complexity of AD it is unlikely that molecular single-target treatments will achieve substantially larger effects than those seen with current β-amyloid-targeting antibodies. Larger effects will most likely only be achieved incrementally by continuous optimization of molecular approaches, patient selection and combinations therapies. To be successful in this regard, drug development must be informed by the use of innovative treatments in real world practice, because full understanding of all facets of novel treatments requires experience and data of real-world care beyond those of clinical trials. Regarding the antibodies under discussion we consider their effects meaningful and potential side effects manageable. We assume that the number of eventually treated patient will only be a fraction of all early AD patients due to narrow eligibility criteria and barriers of access. We strongly endorse the use of these new compound in clinical practice in selected patients with treatment documentation in registries. We understand this as a critical step in advancing the field of AD treatment, and in shaping the health care systems for the new area of molecular-targeted treatment of neurodegenerative diseases.
Competing Interests: D. Aarsland reports personal fees for advice and lectures from Eisai, Biogen, Eli Lilly, EIP Pharma, Roche Diagnostics, Sanofi, and Heptares, and grants from Roche Diagnostics, Sanofi and Evonik. D. Angioni reports being an investigator in clinical trials sponsored by Alector, Alzheon, Biogen, Eisai, Genentech, Green Valley, Hoffmann-La Roche, Janssen, Medesis Pharma, Nestle, Novo Nordisk, Otsuka, Regenlife, Toulouse University Hospital, and UCB Pharma. No direct personal benefit. M. Balasa reports no conflict of interest. M. Boban reports no conflict of interest. K. Bennys reports grants form Alzheon Inc, Araclon Biotech S.L., Biogen, Eisai, Roche Genentech. No personal fees. M. Boada reports fees for advice from Grifols, Araclon, Biotech, Roche, Biogen, Lilly, Merck, Zambon, Novo Nordisk, Bioiberica, Eisai, Servier, and Schwabe Pharma; fees for lectures from Roche, Biogen, Grifols, Nutricia, Araclon Biotech, Servier, and Novo Nordisk. A. Chincarini reports no conflict of interest. S. Engelborghs reports fees from Eisai, icometrix, Novartis, Roche all paid to institution, and personal fees from Roche and Biogen. L. Exalto received personal fees from Julius Clinical and Brain Research Center. A. Felbecker reports personal fees for advisory boards and lectures from Eisai, Eli Lilly, Schwabe Pharma AG, Ompharma, Roche Pharma, Specialty care Therapiezentren AG, and grants from Fujirebio. K. Fliessbach reports no conflict of interest. G.B. Frisoni reports funding through the Private Foundation of Geneva University Hospitals from: A.P.R.A. – Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Ivan Pictet, Genève; Race Against Dementia Foundation, London, UK; Fondation Child Care, Genève; Fondation Edmond J. Safra, Genève; Fondation Minkoff, Genève; Fondazione Agusta, Lugano; McCall Macbain Foundation, Canada; Nicole et René Keller, Genève; Fondation AETAS, Genève. He has received funding through the University of Geneva or Geneva University Hospitals: for IISSs from ROCHE Pharmaceuticals OM Pharma EISAI Pharmaceuticals Biogen Pharmaceuticals and Novo Nordisk; for competitive research projects from: H2020, Innovative Medicines Initiative (IMI), IMI2, Swiss National Science Foundation, and VELUX Foundation as well as payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from: Biogen, Roche, Novo Nordisk, GE HealthCare, all through the institution. A.J. Garza-Martinez reports no conflict of interest. T. Grimmer reports consulting fees from AbbVie, Advantage Therapeutics Alector, Anavex, Biogen, BMS, Cogthera, Iqvia, Noselab, NuiCare, Orphanzyme Eisai, Eli Lilly, Functional Neuromodulation, Grifols, Janssen, Novo Nordisk, Roche Pharma, UCB, and Vivoryon, and lecture fees from Biogen, Eisai, Grifols, Medical Tribune, Schwabe, Synlab, Novo Nordisk, and Roche Pharma. Her served as Principal Investigator in drug trials by AbbVie, Advantage Therapeutics, Alector, Anavex, Biogen, Eli Lilly, Functional Neuromodulation, Roche Pharma, UCB, and Vivoryon; The Institution received payment for study performance. Further grants to his institution from: Biogen and Eisai and Roche Diagnostics. L. Froelich reports grants and personal fees for lectures and advice from Roche, and personal fees for lectures and advice from Eisai, Araclon/Grifols, Eli Lilly, Noselab, NovoNordisk, BioVie, Biogen, MerckSharpe and Dohme, Neurimmune, TauRX, Dr. Willmar Schwabe Otsuka/Avanir, Axon Neuroscience, Pharmatropix, Neuroscios, Vivoryon, Hummingbird, Anavex, and Boehringer Ingelheim. B. Hanseeuw reports personal fees for advice and lectures from Eisai, Roche, Biogen, and grants from Fonds National de la Recherche Scientifique, Fondation Stop Alzheimer, and WEL Research institute (WELBIO). J. Hort reports consulting and lecture fees from Schwabe, Eisai, and Eli Lilly and holds stock options in Alzheon. A. Ivanoiu reports no conflict of interest. F. Jessen has reports honoraria for advisory boards and presentations from Abbvie, AC immune, Biogen, Eli Lilly, Eisai, GE Healthcare, Grifols, Janssen-Cliag and Roche. L. Krajcovicova reports no conflict of interest. S. Klöppel reports fees for advice and lectures from Biogen, Eisai Switzerland, Lundbeck, and OM Pharma. M.G. Kramberger reports no conflict of interest. B. McGuinness reports personal fees from Eisai, Biogen, Eli Lilly, and Nutricia. P. Mecocci reports personal fees for advice and lectures from Lundbeck and Lilly, and non-financial support from Merck. A. de Mendonca reports no conflict of interest. A. Nous reports no conflict of interest. P.J. Dr. Ousset reports research grants from Acadia Pharmaceuticals, Alzheon Inc., Araclon Biotech S.L., AstraZeneca, Biogen, Avanir Pharmaceuticals, Eisai Inc., Eli Lilly, Genentech, Inc., Hoffmann-La Roche, Janssen Research and Development, Merck Sharp and Dohme, Novartis Pharmaceuticals, Shanghai Greenvalley Pharmaceutical Co., TauRx Therapeutics Ltd, UCB Biopharma without personal fee. He reports personal fees for advice from Lilly France. C. Paquet reports no conflict of interest. R. Perneczky reports personal fees for advice and lectures from Biogen, Eisai, Eli Lilly, Grifols, Novo Nordisk Roche, Schwabe, and GSK, and grants from Astra Zeneca, Roche, Janssen Cilag, Eli Lilly, and Takeda. O. Peters reports grants from Alector and Predemtec, grants and personal fees for advice and lectures from Biogen, Eisai, Roche, Noselab, and Novo Nordisk, personal fees for advice and lectures from Grifols, Lilly, Prinnovation, Medtrix, Neurolive, and Neurotransdata. F. Piazza reports consulting fees from Alector, Araclon, Alnylam, Biogen, Lilly, and Roche, and personal honoraria for advisory board membership from Roche, Araclon and Lilly. He holds a patent for the ultrasensitive quantification of anti-amyloid antibodies in human biological fluids. D. Platone reports no conflict of interest. M. Riverol reports personal fees for advice and lectures from Grifols, Nutricia and Esteve. A. Ruiz reports grants from the Instituto de Salud Carlos III (ISCIII), the European Comision-IMI program, the EU-JPND , VLAIO, Janssen, Grifols SA, Roche AG, and Araclon Biotech; and personal fees from Landstenier Genmed, Glenn Biggs Institute, UTHSA, Fundación ADEY, and Novo Nordisk. G. Sacco reports no conflict of interest. I. Santana reports grants from Biogen, and personal fees from Eisai. N. Scarmeas reports grants from NIH, and NovoNordisc. E. Solje reports personal fees from Novartis, Novo Nordisk, Eisai, and Roche and personal fees from Roche. E. Stefanova reports no conflict of interest. S. Sutovsky reports lecture fees from Eisai, Biogen, Schwabe and Krka. M. Tabuas-Pereira reports no conflict of interest. W. van der Flier reports grants from ZonMW, NWO, EU-JPND, EU-IHI, Alzheimer Nederland, Hersenstichting CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences and Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Edwin Bouw fonds, Pasman stichting, stichting Alzheimer and Neuropsychiatrie Foundation, Philips, Biogen MA Inc, Novartis-NL, Life-MI, AVID, Roche BV, Fujifilm, Eisai, Combinostics. She holds the Pasman chair. She is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences and Health (PPP-allowance; #LSHM20106). She is recipient of TAP-dementia (www.tap-dementia.nl), receiving funding from ZonMw (#10510032120003). TAP-dementia receives co-financing from Avid Radiopharmaceuticals and Amprion. All funding is paid to her institution. She reports fees to the institution for lectures from Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape), Novo Nordisk, Springer Healthcare, and European Brain Council. She consulted the Oxford Health Policy Forum CIC, Roche, Biogen MA Inc, and Eisai. All funding is paid to her institution. WF participated in advisory boards of Biogen MA Inc, Roche, and Eli Lilly. WF is member of the steering committee of EVOKE/EVOKE+ (NovoNordisk). All funding is paid to her institution. WF is member of the steering committee of PAVE, and Think Brain Health. WF was associate editor of Alzheimer, Research and Therapy in 2020/2021. WF is associate editor at Brain. T. Welsh is Research and Medical Director of The Research Institute for the Care of Older People (RICE), Bath, UK, which runs a mixture of commercial and non-commercial research activity. Commercial research projects run in the Institute have been funded by: Lilly, Roche, Biogen, Eisai, Janssen, AC Immune, Novo Nordisk, Pfizer, Elan, Immunobrain, Actinogen, and Julius Clinical. A. Wimo report to be the License holder (part) of RUD instrument. B. Winblad reports no conflict of interest.