{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T05:24:34Z","timestamp":1784957074056,"version":"3.55.0"},"reference-count":13,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":63,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;D Transl Res &amp; Clin Interv"],"published-print":{"date-parts":[[2025,7]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n Donanemab is an immunoglobulin G1 antibody that targets an N\u2010terminal truncated form of amyloid beta present in mature plaques. Treatment\u2010emergent (TE) anti\u2010drug antibodies (ADAs) were quantified in donanemab\u2010treated participants from two pivotal clinical trials, and effects of TE ADAs on donanemab pharmacokinetics, efficacy, and safety were assessed.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Data were pooled from the phase 2 TRAILBLAZER\u2010ALZ (NCT03367403) and phase 3 TRAILBLAZER\u2010ALZ 2 trials (NCT04437511). Eligible participants were randomized 1:1 to donanemab (700\u00a0mg for the first three doses, 1400\u00a0mg thereafter) or placebo intravenously every 4 weeks up to 72 weeks. TE ADA\u2010evaluable participants had a non\u2010missing baseline ADA result and \u2265 1 non\u2010missing post\u2010baseline ADA result. TE ADA incidence and effect of titer on pharmacokinetics, amyloid plaque reduction, clinical efficacy (measured by change from baseline of integrated Alzheimer's Disease Rating Scale [iADRS] score and Clinical Dementia Rating Scale Sum of Boxes [CDR\u2010SB]), and safety were assessed.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Of 922 TE ADA\u2010evaluable donanemab\u2010treated participants, 56 (6.1%) had ADAs detected at baseline, and 812 (88.1%) were TE ADA positive. Donanemab clearance increased linearly with logarithm of ADA titer; however, titer did not affect maximum donanemab concentration. Amyloid plaque level was significantly reduced with donanemab versus placebo, irrespective of titer (\n P<\/jats:italic>\n < 0.001 for all). No association was found between ADA presence or titer and donanemab efficacy by iADRS or CDR\u2010SB. Eighty\u2010four of 984 (8.5%) donanemab\u2010treated participants and 4 of 999 (0.4%) placebo\u2010treated participants reported infusion\u2010related reactions (IRRs). All donanemab\u2010treated participants reporting immediate IRRs developed ADAs at some point during the study; however, 90.5% of TE ADA\u2010positive participants did not experience IRRs.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Most participants were TE ADA positive. TE ADAs increased donanemab clearance but did not have clinically meaningful impact on plaque reduction or efficacy. While all participants reporting IRRs developed ADAs at some point during the study, the majority of participants with ADAs did not experience IRRs.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n In pivotal trials, most donanemab\u2010treated participants were treatment\u2010emergent anti\u2010drug antibody (TE ADA) positive.<\/jats:p>\n <\/jats:list-item>\n \n TE ADAs increased donanemab clearance but did not impact plaque reduction\/efficacy.<\/jats:p>\n <\/jats:list-item>\n \n All participants reporting infusion\u2010related reactions (IRRs) developed ADAs at some point during the study.<\/jats:p>\n <\/jats:list-item>\n \n However, the majority of participants with ADAs did not experience IRRs.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/trc2.70149","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T09:15:51Z","timestamp":1756804551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Donanemab immunogenicity in participants with early symptomatic Alzheimer's disease"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5320-1023","authenticated-orcid":false,"given":"Garrett R.","family":"Mullins","sequence":"first","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Ardayfio","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivelina","family":"Gueorguieva","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Bracknell UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Anglin","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Bailey","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyi","family":"Chua","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia D.","family":"Evans","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emel Serap Monkul","family":"Nery","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashna","family":"Khanna","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn A.","family":"Brooks","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Sims","sequence":"additional","affiliation":[{"name":"Eli Lilly & Company Lilly Corporate Center Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2100708"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_10_4_1","unstructured":"Eli Lilly and Company.KISUNLA\u2122 [package 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Protein Products \u2014 Developing and Validating Assays for Anti\u2010Drug Antibody Detection.2019."},{"key":"e_1_2_10_13_1","unstructured":"GueorguievaI ChuaL ChowK MullinsG ArdayfioP Brown\u2010AugsburgerPL et\u00a0al. editors.Flat dosing of donanemab provides serum exposures within the therapeutic window and lack of Phase 1 APOE effect of CSF exposures in participants with Alzheimer's disease.International Conference on Alzheimer's and Parkinson's Diseases 2024;Lisbon Portugal and online."},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.2.3.11641"}],"container-title":["Alzheimer's & Dementia: Translational Research & Clinical 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