{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T17:30:19Z","timestamp":1788283819469,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&D Transl Res & Clin Interv"],"published-print":{"date-parts":[[2025,4]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n We aimed to determine the clinical efficacy of treating apolipoprotein E (ApoE) \u03b54 homozygotes with recently approved anti\u2010amyloid antibodies.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Data were derived from supplementary analyses in the regulatory studies Clarity (lecanemab) and TRAILBLAZER\u2010ALZ2 (donanemab). We used Bayesian reanalysis with an independent t\u2010statistic to determine evidence for or against an effect of antibody treatment on Clinical Dementia Rating scale Sum of Boxes (CDR\u2010SB) in ApoE \u03b54 homozygotes, and a Bayesian random\u2010effect meta\u2010analysis to determine the effect size.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n The Bayesian reanalysis showed moderate evidence of no effect for both antibodies. For donanemab and lecanemab, the odds of no difference in treatment effect were nearly three times greater than the odds of a difference. The meta\u2010analysis revealed a small effect of \u22120.06 CDR\u2010SB points in favor of treatment with a moderate heterogeneity estimate. The Bayes factor was 0.26, indicating that the absence of an effect was almost four times more likely than the presence of an effect.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n The most likely explanation for our results is the lack of a treatment effect for lecanemab and donanemab in ApoE\n \u03b5<\/jats:italic>\n 4 homozygotes. This could reflect inadequate exposure to the antibody due to more severe side effects, subsequent treatment interruptions, and lower dosing or a biologically driven lack of efficacy in a genetically determined disease. Our results support the view that excluding these cases from treatment is justifiable because of the higher risk of side effects and the lack of clinical efficacy.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Lecanemab and donanemab were clinically ineffective in ApoE \u03b54 homozygotes.<\/jats:p>\n <\/jats:list-item>\n \n ApoE \u03b54 homozygotes should not receive these treatments due to inefficacy.<\/jats:p>\n <\/jats:list-item>\n \n Future trials should adopt Bayesian analysis strategies.<\/jats:p>\n <\/jats:list-item>\n \n Bayesian analysis provides evidence for or against treatment effects.<\/jats:p>\n <\/jats:list-item>\n \n Bayesian inference provides clinically interpretable results.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/trc2.70083","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T01:31:08Z","timestamp":1744248668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical efficacy of anti\u2010amyloid antibodies in apolipoprotein E \u03b54 homozygotes: A Bayesian reanalysis of lecanemab and donanemab phase 3 results"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3586-3194","authenticated-orcid":false,"given":"Stefan","family":"Teipel","sequence":"first","affiliation":[{"name":"German Center of Neurodegenerative Diseases (DZNE), Rostock\/Greifswald Rostock Germany"},{"name":"Department of Psychosomatic Medicine University Medicine Rostock Rostock Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology Capital Medical University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara","family":"Khachaturian","sequence":"additional","affiliation":[{"name":"Brain Watch Coalition Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2023.30"},{"key":"e_1_2_8_5_1","unstructured":"FDA.Lequembi.2023.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/761269s000lbl.pdf"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2018.2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230589"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100708"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-021-00813-8"},{"key":"e_1_2_8_10_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions","author":"Higgins JPT","year":"2020"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3758\/s13423-020-01798-5"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202308-1455VP"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202310-1757VP"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v093.i06"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2014.08.012"},{"key":"e_1_2_8_16_1","unstructured":"EvansCD ZimmerJA WesselsAM et\u00a0al.Efficacy of Donanemab by APOE \u03b54 carrier status in TRAILBLAZER\u2010ALZ 2 a Phase 3 randomized Clinical Trial in Early Symptomatic Alzheimer's Disease. In:Clinical Trials on Alzheimer's Disease (CTAD)\u201416th Annual Conference Boston Massachusetts USA.2023."},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02931-w"},{"key":"e_1_2_8_18_1","unstructured":"European Medicinal Agency (EMA).The European Medicines Agency has recommended the refusal of the marketing authorisation for Leqembi.https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/leqembi#:~:text=The%20European%20Medicines%20Agency%20has%20recommended%20the%20refusal Agency%20issued%20its%20opinion%20on%2025%20July%202024.2024"}],"container-title":["Alzheimer's & Dementia: Translational Research & Clinical Interventions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/trc2.70083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T09:24:36Z","timestamp":1761470676000},"score":1,"resource":{"primary":{"URL":"https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1002\/trc2.70083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/trc2.70083"],"URL":"https:\/\/doi.org\/10.1002\/trc2.70083","archive":["Portico"],"relation":{},"ISSN":["2352-8737","2352-8737"],"issn-type":[{"value":"2352-8737","type":"print"},{"value":"2352-8737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70083"}}