ADUCANUMAB IN THE TREATMENT OF ALZHEIMER'S DISEASE
Abstract
Introduction: Alzheimer's disease (AD) is a chronic pathology, characterized by progressive cognitive impairment and neurobehavioral changes. Common treatments for Alzheimer's disease are symptomatic in focus and have modest benefits. On June 7, 2021, the US regulatory agency Food And Drug Administration (FDA) approved the use of the drug Aducanumab. Objectives: to analyze the main studies about Aducanumab and its effectiveness in the treatment of Alzheimer's disease. Materials and methods: This is an integrative review, in which the guiding question was "How effective is Aducanumab in the treatment of Alzheimer's?". The search for articles was carried out in the main databases (PubMed and Scielo) using the terms “Aducanumab”, “treatment” and “Alzheimer's”, combined by Boolean operators. Results and Discussion: Over the past 25 years, several Aβ-targeted drugs have failed to demonstrate clinical efficacy in trials, including five anti-Aβ antibodies: bapineuzumab, solanezumab, crenezumab, ponezumab, and gantenerumab. Aducanumab is part of a new generation of anti-Aβ monoclonal antibodies that specifically target Aβ aggregates. Monoclonal antibodies against Aβ as a class statistically improved cognition by a small effect size and strongly decreased brain amyloid burden and p181-tau in cerebrospinal fluid suggesting some degree of disease modification, at the expense of increased risk of imaging abnormalities related to amyloid. Aducanumab has produced promising clinical and biomarker results. Conclusion: Despite the controversy, it is clear that Aducanumab significantly reduces Aβ in the brain, one of the hallmarks of AD. Furthermore, the results also showed that Aducanumab decreases brain levels of tau.
Author Biographies
Centro Universitário Claretiano - Rio Claro.
Centro Universitário Claretiano - Rio Claro.
Universidade Professor Edson Antônio Velano - UNIFENAS.
Universidade Professor Edson Antônio Velano - UNIFENAS.
Centro Universitário Clarentiano - Rio Claro.
Universidade Professor Edson Antônio Velano - UNIFENAS.
Universidade Professor Edson Antônio Velano - UNIFENAS.
Universidade Professor Edson Antônio Velano - UNIFENAS.
Universidade José do Rosário Vellano - UNIFENAS.
Universidade Professor Edson Antônio Velano - UNIFENAS.
References
Agatonovic-Kustrin, S., Kettle, C., & Morton, D. W. (2018). A molecular approach in drug development for Alzheimer’s disease. Biomedicine & Pharmacotherapy, 106, 553-565.
Avgerinos KI, Ferrucci L, Kapogiannis D. Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer's disease. Ageing Res Rev. 2021 Jul;68:101339. Epub 2021 Apr 5. PMID: 33831607; PMCID: PMC8161699 DOI: https://doi.org/10.1016/j.arr.2021.101339
Biogen. Update on the phase 4 confirmatory study of ADUHELM®. Biogen; 2021. Available from: https://investors.biogen.com/news-releases/news-release-details/update-phase-4-confirmatory-study-aduhelmr Acesso em agosto de 2023.
Biogen. Update on the Phase 4 ENVISION confirmatory study of ADUHELM® | biogen. Biogen; 2022. Available from: https://investors.biogen.com/news-releases/news-release-details/update-phase-4-envision-confirmatory-study-aduhelmr Acesso em agosto de 2023.
Chiao P, Bedell BJ, Avants B, Zijdenbos AP, Grand'Maison M, O'Neill P, O'Gorman J, Chen T, Koeppe R. Impact of Reference and Target Region Selection on Amyloid PET SUV Ratios in the Phase 1b PRIME Study of Aducanumab. J Nucl Med. 2019 Jan;60(1):100-106. Epub 2018 May 18. PMID: 29777003 DOI: https://doi.org/10.2967/jnumed.118.209130
Dhillon S. Aducanumab: First Approval. Drugs. 2021 Aug;81(12):1437-1443. Erratum in: Drugs. 2021 Sep;81(14):1701. PMID: 34324167 DOI: https://doi.org/10.1007/s40265-021-01569-z
Fleisher AS, Joshi AD, Sundell KL, et al. Use of white matter reference regions for detection of change in florbetapir positron emission tomography from completed phase 3 solanezumab trials. Alzheimers Dement. 2017; 13:1117–1124.
J. Ferrero, L. Williams, H. Stella, K. Leitermann, A. Mikulskis, J. O’Gorman, et al. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer's disease Alzheimer Dement Transl Res Clin Interv, 2 (2016), pp. 169-176, 10.1016/j.trci.2016.06.002
Landau SM, Breault C, Joshi AD, et al. Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. J Nucl Med. 2013; 54:70–77.
Santos, M. L. D., Quintilio, W., Manieri, T. M., Tsuruta, L. R., & Moro, A. M. (2018). Advances and challenges in therapeutic monoclonal antibodies drug development. Brazilian Journal of Pharmaceutical Sciences, 54.
Scheltens P, De Strooper B, Kivipelto M, Holstege H, Chételat G, Teunissen CE, Cummings J, van der Flier WM. Alzheimer's disease. Lancet. 2021 Apr 24;397(10284):1577-1590. Epub 2021 Mar 2. PMID: 33667416; PMCID: PMC8354300 DOI: https://doi.org/10.1016/S0140-6736(20)32205-4
Vaz M, Silva V, Monteiro C, Silvestre S. Role of Aducanumab in the Treatment of Alzheimer's Disease: Challenges and Opportunities. Clin Interv Aging. 2022 May 18;17:797-810. PMID: 35611326; PMCID: PMC9124475 DOI: https://doi.org/10.2147/CIA.S325026
Villain N, Planche V, Levy R. High-clearance anti-amyloid immunotherapies in Alzheimer's disease. Part 1: Meta-analysis and review of efficacy and safety data, and medico-economical aspects. Rev Neurol (Paris). 2022 Dec;178(10):1011-1030. Epub 2022 Sep 29. PMID: 36184326 DOI: https://doi.org/10.1016/j.neurol.2022.06.012
Zhang XX, Tian Y, Wang ZT, Ma YH, Tan L, Yu JT. The Epidemiology of Alzheimer's Disease Modifiable Risk Factors and Prevention. J Prev Alzheimers Dis. 2021;8(3):313-321. PMID: 34101789 DOI: https://doi.org/10.14283/jpad.2021.15
