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Cited by 17Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

A Systematic Review of the Efficacy and Safety of Anti-amyloid Monoclonal Antibodies in Alzheimer's Disease

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Chundu, Umesh C, Thiriveedhi, Sree Ram, Bhatti, Chetanya, Mupparaju, Jaya Sai, Otinashvili, Nina, Gelishvili, Elene·2025·Cureus
DOI 10.7759/cureus.85377PMC PMC12227895
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Abstract

Monoclonal antibody (mAb) therapies targeting amyloid-beta (Aβ) plaques have gained prominence over the past decade as potential disease-modifying treatments for Alzheimer's disease (AD), leading to major regulatory approvals and global debate. Nonetheless, the central question persists: does this emerging therapy have a justified role in the treatment protocol for AD? This systematic review evaluates the efficacy and safety of these agents across phase II and III clinical trials conducted in the past decade (2014-2024), aligning with the timeline when disease-modifying therapies gained momentum. A systematic search was performed across PubMed and the Cochrane Library to identify phase II and III randomized controlled trials (RCTs) conducted between January 2014 and December 2024. The inclusion criteria focused on studies that evaluated cognitive outcomes using scales such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Mini-Mental State Examination (MMSE). Additionally, trials assessing biomarkers, including CSF measures and PET imaging, were included. Safety outcomes, particularly amyloid-related imaging abnormalities (ARIA), were also systematically analyzed. Due to heterogeneity in outcome measures, a narrative synthesis was conducted. Sixteen RCTs met the inclusion criteria. Lecanemab reduced amyloid burden with 81% of patients achieving amyloid-negative PET scans (Clarity AD trial) and showed a 27% reduction in cognitive decline on the ADCOMS scale. While statistically significant, the 27% ADCOMS (Alzheimer's Disease Composite Score) reduction warrants comparison to MCID (minimal clinically important difference) thresholds (e.g., ~0.5-1.0 points for CDR-SB in early AD) to assess real-world impact. Donanemab demonstrated 76% plaque clearance and a 35% slowing in cognitive decline in early AD patients. Aducanumab showed dose-dependent effects on plaque clearance but had inconsistent cognitive outcomes and higher ARIA rates. Recent mAb trials provide promising evidence for disease modification in early AD stages, particularly with lecanemab and donanemab. However, variability in cognitive outcomes and safety concerns warrant cautious interpretation and long-term validation.

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Research works printed but not linked: 19

  1. [1]Alzheimer’s Disease Harrison's Principles of Internal Medicine Seeley WW Miller BL McGraw-Hill Education 2020 https://accessmedicine.mhmedical.com/content.aspx?bookid=2129&sectionid=192532255
  2. [2]Amyloid-beta: a crucial factor in Alzheimer's disease Med Princ Pract Sadigh-Eteghad S Sabermarouf B Majdi A Talebi M Farhoudi M Mahmoudi J 1 10 24 2015 PMC5588216 25471398
  3. [3]Viewpoint: crosstalks between neurofibrillary tangles and amyloid plaque formation Ageing Res Rev Luan K Rosales JL Lee KY 174 181 12 2013 22728532
  4. [4]A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease Nat Rev Neurol Panza F Lozupone M Logroscino G Imbimbo BP 73 88 15 2019 30610216
  5. [5]Two randomized phase 3 studies of aducanumab in early Alzheimer's disease J Prev Alzheimers Dis Budd Haeberlein S Aisen PS Barkhof F 197 210 9 2022 35542991
  6. [7]Lecanemab in early Alzheimer's disease N Engl J Med van Dyck CH Swanson CJ Aisen P 9 21 388 2023 36449413
  7. [9]Prisma2020: An R package and shiny app for producing Prisma 2020-compliant flow diagrams, with interactivity for optimised digital transparency and open synthesis Campbell Syst Rev Haddaway NR Page MJ Pritchard CC McGuinness LA 0 18 2022 PMC8958186 36911350
  8. [10]RoB 2: a revised Cochrane risk-of-bias tool for randomized trials | Cochrane Bias 4 2025 2025 https://methods.cochrane.org/bias/resources/rob-2-revised-cochrane-risk-bias-tool-randomized-trials. 32562833
  9. [11]Amyloid-related imaging abnormalities in 2 Phase 3 studies evaluating aducanumab in patients with early Alzheimer disease JAMA Neurol Salloway S Chalkias S Barkhof F 13 21 79 2022 34807243 PMC8609465
  10. [12]Long-term safety and tolerability of bapineuzumab in patients with Alzheimer's disease in two phase 3 extension studies Alzheimers Res Ther Ivanoiu A Pariente J Booth K 24 8 2016 27334799 PMC4918115
  11. [13]Central review of amyloid-related imaging abnormalities in two phase III clinical trials of bapineuzumab in mild-to-moderate Alzheimer's disease patients J Alzheimers Dis Ketter N Brashear HR Bogert J 557 573 57 2017 28269765
  12. [14]Long-term follow up of patients with mild-to-moderate Alzheimer's disease treated with bapineuzumab in a phase III, open-label, extension study J Alzheimers Dis Salloway SP Sperling R Fox NC 689 707 64 2018 29914022
  13. [16]A phase II, randomized, double-blind, placebo-controlled study of safety, pharmacokinetics, and biomarker results of subcutaneous bapineuzumab in patients with mild to moderate Alzheimer's disease J Alzheimers Dis Brody M Liu E Di J 1509 1519 54 2016 27589523
  14. [17]Evaluating the safety and efficacy of crenezumab vs placebo in adults with early Alzheimer disease: two phase 3 randomized placebo-controlled trials JAMA Neurol Ostrowitzki S Bittner T Sink KM 1113 1121 79 2022 36121669 PMC9486635
  15. [18]Donanemab in early symptomatic Alzheimer disease: the TRAILBLAZER-ALZ 2 randomized clinical trial J Am Med Assoc Sims JR Zimmer JA Evans CD 512 527 330 2023 PMC10352931 37459141
  16. [19]Donanemab population pharmacokinetics, amyloid plaque reduction, and safety in participants with Alzheimer's disease Clin Pharmacol Ther Gueorguieva I Willis BA Chua L 1258 1267 113 2023 36805552
  17. [21]Lecanemab in patients with early Alzheimer's disease: detailed results on biomarker, cognitive, and clinical effects from the randomized and open-label extension of the phase 2 proof-of-concept study Alzheimers Res Ther McDade E Cummings JL Dhadda S 191 14 2022 36544184 PMC9768996
  18. [24]Safety and efficacy of semorinemab in individuals with prodromal to mild Alzheimer disease: a randomized clinical trial JAMA Neurol Teng E Manser PT Pickthorn K 758 767 79 2022 35696185 PMC9194753
  19. [25]Assessment of efficacy and safety of Zagotenemab: results from PERISCOPE-ALZ, a Phase 2 study in early symptomatic Alzheimer disease Neurology Fleisher AS Munsie LM Perahia DG 0 102 2024 PMC11067698 38386949

Cited by

Sorted by citations

Authors
Chundu, U. C., Thiriveedhi, S. R., Bhatti, C., Mupparaju, J. S., Otinashvili, N., & Gelishvili, E.
Affiliations
  • Guntur Medical College (IN)
  • NRI Medical College (IN)
  • Tbilisi State Medical University (GE)
ORCID
Venue
Cureus
Publisher
Springer Science and Business Media LLC
Published
2025-06-04
Volume
17
Issue
6
Pages
e85377-e85377
ISSN
2168-8184 (ISSN-L)
DOI
10.7759/cureus.85377
PMC
PMC12227895
OpenAlex
W4411074804
Cited by
17
References
6
Citations by year
2026: 14 · 2025: 3
FWCI
1.96
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cureus (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
anti-amyloid monoclonal antibodies, Alzheimer's disease, amyloid plaques, lecanemab, donanemab, aducanumab, amyloid-related imaging abnormalities, cognitive decline, amyloid PET, cerebrospinal fluid biomarkers, disease-modifying therapy, treatment efficacy, drug safety

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