{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:28:10Z","timestamp":1792096090059,"version":"4.4.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"3","funder":[{"DOI":"10.13039\/100006492","name":"Intramural Research Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004598","name":"IRP","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004598","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research University College Hospital London Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S021418\/1"],"award-info":[{"award-number":["MR\/S021418\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer\u2019s disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer\u2019s disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer\u2019s disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer\u2019s disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer\u2019s disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad175","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T19:55:07Z","timestamp":1685649307000},"source":"Crossref","is-referenced-by-count":57,"title":["Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer\u2019s disease"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-2758","authenticated-orcid":false,"given":"Kathy Y","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Psychiatry, University College London , London W1T 7NF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7429-4289","authenticated-orcid":false,"given":"Nicolas","family":"Villain","sequence":"additional","affiliation":[{"name":"AP-HP.Sorbonne Universit\u00e9, Institut de la M\u00e9moire et de la Maladie d\u2019Alzheimer, D\u00e9partement de Neurologie, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re , 75013 Paris , France"},{"name":"Sorbonne Universit\u00e9, Institut national de la Sant\u00e9 et de la Recherche Medical (INSERM) U1127, Centre National de la Recherche Scientifique (CNRS) 7225, Institut du Cerveau\u2014ICM , 75013 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3479-2427","authenticated-orcid":false,"given":"Scott","family":"Ayton","sequence":"additional","affiliation":[{"name":"Melbourne Dementia Research Centre, Florey Institute of Neuroscience and Mental Health, The University of Melbourne , Parkville, VIC 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah F","family":"Ackley","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California San Francisco , San Francisco, CA 94158 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3713-227X","authenticated-orcid":false,"given":"Vincent","family":"Planche","sequence":"additional","affiliation":[{"name":"Univ. Bordeaux, CNRS, UMR 5293, Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives , F-33000 Bordeaux , France"},{"name":"Centre M\u00e9moire Ressources Recherches, P\u00f4le de Neurosciences Cliniques , CHU de Bordeaux, F-33000 Bordeaux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Howard","sequence":"additional","affiliation":[{"name":"Division of Psychiatry, University College London , London W1T 7NF , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-2299","authenticated-orcid":false,"given":"Madhav","family":"Thambisetty","sequence":"additional","affiliation":[{"name":"Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"issue":"10","key":"2023062817062410400_fcad175-B1","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1001\/jamainternmed.2021.4607","article-title":"Approval of aducanumab for Alzheimer disease-the FDA's perspective","volume":"181","author":"Dunn","year":"2021","journal-title":"JAMA Intern Med"},{"issue":"2","key":"2023062817062410400_fcad175-B2","first-page":"197","article-title":"Two randomized phase 3 studies of aducanumab in early Alzheimer\u2019s disease","volume":"9","author":"Budd Haeberlein","year":"2022","journal-title":"J Prev Alzheimers Dis"},{"issue":"1","key":"2023062817062410400_fcad175-B3","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1001\/jamaneurol.2021.4161","article-title":"Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease","volume":"79","author":"Salloway","year":"2022","journal-title":"JAMA Neurol"},{"key":"2023062817062410400_fcad175-B4","author":"Terry"},{"issue":"1","key":"2023062817062410400_fcad175-B5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13195-021-00813-8","article-title":"A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer's disease with lecanemab, an anti-abeta protofibril antibody","volume":"13","author":"Swanson","year":"2021","journal-title":"Alzheimers Res Ther"},{"issue":"1","key":"2023062817062410400_fcad175-B6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1056\/NEJMoa2212948","article-title":"Lecanemab in early Alzheimer's disease","volume":"388","author":"van Dyck","year":"2023","journal-title":"N Engl J Med"},{"issue":"6624","key":"2023062817062410400_fcad175-B7","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1126\/science.adg1899","article-title":"Alzheimer's drug stirs excitement-and concerns","volume":"378","author":"Couzin-Frankel","year":"2022","journal-title":"Science"},{"issue":"5","key":"2023062817062410400_fcad175-B8","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1056\/NEJMc2215148","article-title":"Multiple cerebral hemorrhages in a patient receiving lecanemab and treated with t-PA for stroke","volume":"388","author":"Reish","year":"2023","journal-title":"N Engl J Med"},{"issue":"18","key":"2023062817062410400_fcad175-B9","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","article-title":"Donanemab in early Alzheimer's disease","volume":"384","author":"Mintun","year":"2021","journal-title":"N Engl J Med"},{"issue":"1","key":"2023062817062410400_fcad175-B10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13195-017-0318-y","article-title":"A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease","volume":"9","author":"Ostrowitzki","year":"2017","journal-title":"Alzheimers Res Ther"},{"issue":"7","key":"2023062817062410400_fcad175-B11","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1038\/s41591-021-01369-8","article-title":"A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer's disease","volume":"27","author":"Salloway","year":"2021","journal-title":"Nat Med"},{"key":"2023062817062410400_fcad175-B12"},{"key":"2023062817062410400_fcad175-B13"},{"issue":"10","key":"2023062817062410400_fcad175-B14","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1111\/jgs.17390","article-title":"\u201cReal world\u201d eligibility for aducanumab","volume":"69","author":"Canevelli","year":"2021","journal-title":"J Am Geriatr Soc"},{"issue":"22","key":"2023062817062410400_fcad175-B15","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1056\/NEJMp2113679","article-title":"Why is aducanumab priced at $56,000 per patient? 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