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CC BY 4.0 · Arq Neuropsiquiatr 2025; 83(05): s00451808082
DOI: 10.1055/s-0045-1808082
Point of View

Monoclonal antibodies against beta-amyloid protein (lecanemab and donanemab) should not be used in the treatment of Alzheimer's disease

Ricardo Nitrini 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, Grupo de Neurologia Cognitiva e do Comportamento, São Paulo SP, Brazil.
,
Adalberto Studart-Neto 
1   Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, Grupo de Neurologia Cognitiva e do Comportamento, São Paulo SP, Brazil.
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Abstract

Two antiamyloid monoclonal antibodies (mAbs), lecanemab and donanemab, were recently launched for treatment of Alzheimer's disease (AD). These mAbs remove amyloid protein from the brain and cause statistically significant improvement in cognitive/functional tests, meaning a change in evolution of AD. This is important to reinforce the amyloid cascade hypothesis and to further concentrate studies on the pathways from the deposition of the beta-amyloid protein to synaptic loss and neuronal death. However, it is necessary to evaluate whether the results are clinically important. Analysis of the clinical trials showed that the statistically significant differences over placebo did not reach the minimum clinically important difference that would be meaningful for patients, caregivers and clinicians. Besides, the incidence of adverse events is high and potentially severe. Although there are reasons to celebrate this first step towards disease-modifying therapies for AD, lecanemab and donanemab should not be used to treat AD in clinical pratice.

Keywords

Alzheimer Disease - Therapeutics - Antibodies, Monoclonal - Amyloid Cascade - Lecanemab - Donanemab - Minimum Clinically Important Difference

Authors' Contributions

RN: study design, data collection, analysis and/or interpretation of data, writing – original draft, and writing – review & editing; and ASN: data collection, analysis and/or interpretation of data, writing – original draft, and writing – review & editing.


This article is part of a debate series on Amyloid, featuring different perspectives. Check out the other points of view: https://doi.org/10.1055/s-0045-1807718 and https://doi.org/10.1055/s-0045-1808083.


Editor-in-Chief: Hélio A. G. Teive.


Associate Editor: Carlos Henrique Ferreira Camargo.


Guest Editor: Paulo Caramelli.




Publication History

Received: 13 February 2025

Accepted: 27 February 2025

Article published online:
09 May 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

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Bibliographical Record
Ricardo Nitrini, Adalberto Studart-Neto. Monoclonal antibodies against beta-amyloid protein (lecanemab and donanemab) should not be used in the treatment of Alzheimer's disease. Arq Neuropsiquiatr 2025; 83: s00451808082.
DOI: 10.1055/s-0045-1808082
 

  • References

  • 1 Russell BAW. Video for future generations,. 1959 . Available from: https://www.nitch.com/posts/1498230347
    Search in Google Scholar
  • 2 Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T. et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 1999; 400 (6740) 173-177
    CrossrefPubMedSearch in Google Scholar
  • 3 Heneka MT, Morgan D, Jessen F. Passive anti-amyloid β immunotherapy in Alzheimer's disease-opportunities and challenges. Lancet 2024; 404 (10468): 2198-2208
    CrossrefPubMedSearch in Google Scholar
  • 4 Wicker A, Shriram J, Decourt B, Sabbagh MN. Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years. Neurol Ther 2024; 13 (06) 1571-1595
    CrossrefPubMedSearch in Google Scholar
  • 5 Castellani RJ, Perry G. The Teflon hypothesis. Brain Commun 2023; 5 (04) fcad203
    CrossrefPubMedSearch in Google Scholar
  • 6 Van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M. et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med 2023; 388 (01) 9-21
    CrossrefPubMedSearch in Google Scholar
  • 7 Mintun MA, Lo AC, Evans CD, Wessels AM, Ardayfio PA, Andersen SW. et al. Donanemab in Early Alzheimer's Disease. N Engl J Med 2021; 384 (18) 1691-1704
    CrossrefPubMedSearch in Google Scholar
  • 8 Sims JR, Zimmer JA, Evans CD, Lu M, Ardayfio P, Sparks J. et al. TRAILBLAZER-ALZ 2 Investigators. Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA 2023; 330 (06) 512-527
    CrossrefPubMedSearch in Google Scholar
  • 9 Andrews JS, Desai U, Kirson NY, Zichlin ML, Ball DE, Matthews BR. Disease severity and minimal clinically important differences in clinical outcome assessments for Alzheimer's disease clinical trials. Alzheimers Dement (N Y) 2019; 5: 354-363
    CrossrefPubMedSearch in Google Scholar
  • 10 Liu KY, Schneider LS, Howard R. The need to show minimum clinically important differences in Alzheimer's disease trials. Lancet Psychiatry 2021; 8 (11) 1013-1016
    CrossrefPubMedSearch in Google Scholar
  • 11 Willis B, Hussein Z, Hayato S, Takenaka O, Penner N, Yasuda S, Reyderman L. Exposure-response modeling to describe the change in brain amyloid following lecanemab administration in patients with early Alzheimer's disease. Alzheimers Dement 2023; 19 (Suppl. 21) e080393
    CrossrefSearch in Google Scholar
  • 12 Wang G, Cutter G, Oxtoby NP, Shan G, Wang W, Mangal B. et al. Statistical considerations when estimating time-saving treatment effects in Alzheimer's disease clinical trials. Alzheimers Dement 2024; 20 (08) 5421-5433
    CrossrefPubMedSearch in Google Scholar
  • 13 Goldberg TE, Lee S, Devanand DP, Schneider LS. Comparison of relative change with effect size metrics in Alzheimer's disease clinical trials. J Neurol Neurosurg Psychiatry 2023; 95 (01) 2-7
    CrossrefPubMedSearch in Google Scholar
  • 14 Kurkinen M. Anti-amyloid therapies do not slow Alzheimer's disease progression. Dement Neuropsychol 2024; 17: e20230099
    CrossrefPubMedSearch in Google Scholar
  • 15 Jack Jr CR, Andrews JS, Beach TG, Buracchio T, Dunn B, Graf A. et al. Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement 2024; 20 (08) 5143-5169
    CrossrefPubMedSearch in Google Scholar
  • 16 Dantas JM, Mutarelli A, Navalha DDP, Dagostin CS, Romeiro PHCL, Felix N. et al. Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer's disease: a systematic review and meta-analysis. Neurol Sci 2024; 45 (06) 2461-2469
    CrossrefPubMedSearch in Google Scholar
  • 17 A donanemab (LY3002813) Study in Participants With Preclinical Alzheimer's Disease (TRAILBLAZER-ALZ 3). NCT05026866.
  • 18 Reish NJ, Jamshidi P, Stamm B, Flanagan ME, Sugg E, Tang M. et al. Multiple Cerebral Hemorrhages in a Patient Receiving Lecanemab and Treated with t-PA for Stroke. N Engl J Med 2023; 388 (05) 478-479
    CrossrefPubMedSearch in Google Scholar
  • 19 van der Flier WM. Clinical aspects of microbleeds in Alzheimer's disease. J Neurol Sci 2012; 322 (1-2): 56-58
    CrossrefPubMedSearch in Google Scholar
  • 20 Vázquez-Justes D, Aguirregoicoa I, Fernandez L, Carnes-Vendrell A, Dakterzada F, Sanjuan L. et al. Clinical impact of microbleeds in patients with Alzheimer's disease. BMC Geriatr 2022; 22 (01) 774
    CrossrefPubMedSearch in Google Scholar
  • 21 Pittock RR, Aakre JA, Castillo AM, Ramanan VK, Kremers WK, Jack Jr CR. et al. Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging. Neurology 2023; 101 (19) e1837-e1849
    PubMedSearch in Google Scholar