Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer’s Disease: A Systematic Review and Network Meta-Analysis
Abstract
Background Recent clinical trials of anti-Aβ monoclonal antibodies (mAbs) in the treatment of early Alzheimer's disease (AD) have produced encouraging cognitive and clinical results. The purpose of this network meta-analysis (NMA) was to compare and rank mAb drugs according to their efficacy and safety.Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials testing various mAbs for the treatment of cognitive decline in patients with AD, up to March 31, 2023. R software (version 4.2.3) along with JAGS and STATA software (version 15.0) were used for statistical analysis. Odds ratio (OR) for binary variables, mean difference (MD) for continuous variables, and their 95% confidence intervals (CI) were utilized to estimate treatment effects and rank probabilities for each mAb in terms of safety and efficacy outcomes. We calculated the surface under the cumulative ranking area (SUCRA) to evaluate each mAb, with higher SUCRA values indicating better efficacy or lower likelihood of adverse events.Results Thirty-three randomized controlled trials with a total of 21,087 patients were included in the current NMA, involving eight different mAbs. SUCRA values showed that aducanumab (87.01% and 99.37%, respectively) was the most likely to achieve the best therapeutic effect based on the changes of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. Donanemab (88.50% and 99.00%, respectively) performed better than other therapies for Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Positron Emission Tomography-Standardized Uptake Value ratio (PET-SUVr). Lecanemab (87.24%) may be the most promising way to slow down the decrease of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score. In the analysis of the incidence of adverse events (subjects with any treatment-emergent adverse event), gantenerumab (89.12%) had the least potential for adverse events, while lecanemab (0.79%) may cause more adverse events. Solanezumab (95.75% and 80.38%, respectively) had the lowest incidence of amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) and by cerebral microhemorrhages (ARIA-H) of the included immunotherapies. While SUCRA values provided a comprehensive measure of treatment efficacy, the inherent statistical uncertainty required careful analysis in clinical application.Conclusion Despite immunotherapies significantly increasing the risks of adverse events and ARIA, the data suggest that mAbs can effectively improve the cognitive function of patients with mild and moderate AD. According to the NMA, aducanumab was the most likely to achieve significant improvements in different cognitive and clinical assessments (statistically improved MMSE and CDR-SB), followed by donanemab (statistically improved ADAS-Cog, and PET-SUVr) and lecanemab (statistically improved ADCS-ADL).
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According to the amyloid cascade hypothesis, tau protein tangles and neuroinflammation are brought on by Aβ aggregation, which in turn leads to neuronal death and cognitive decline.
“According to the amyloid cascade hypothesis, tau protein tangles and neuroinflammation are brought on by Aβ aggregation, which in turn leads to neuronal death and cognitive decline [90,91,92].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [92]
Aducanumab was more likely than comparator to cause ARIA-E (edema).
“Aducanumab in particular was more likely to cause ARIA-E (edema) [37,92].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [92]
Both aducanumab and lecanemab slowed cognitive decline and reduced amyloid plaques, but were more likely to cause ARIAs, thought to be the most significant side effect of both drugs.
“While both aducanumab and lecanemab slowed cognitive decline and reduced amyloid plaques, they were more likely to cause amyloid-related imaging abnormalities (ARIAs), which are thought to be the most significant side effect of both drugs.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [92]
Meta-analyses of monoclonal antibodies assessed their effectiveness and safety for AD.
“The effectiveness and safety of several monoclonal antibodies used to treat AD were assessed by meta-analyses of monoclonal antibodies.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [92]
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- Authors
- Qiao, Y., Gu, J., Yu, M., Chi, Y., & Ma, Y.
- Affiliations
- Sheng Jing Hospital (CN)
- Corresponding author
- Ma, Ying
- Venue
- CNS Drugs
- Published
- 2024-03
- Volume
- 38
- Issue
- 3
- Pages
- 169-192
- ISSN
- 1172-7047 (ISSN-L)
- 1179-1934
- OpenAlex
- W4392363504
- Cited by
- 38
- References
- 70
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 11
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Funders
- the Shenyang Science and Technology Program (grant number 20-205-4-090)
- 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
- Alzheimer's disease, anti-amyloid monoclonal antibodies, cognitive decline, aducanumab, donanemab, lecanemab, gantenerumab, solanezumab, amyloid-beta, treatment efficacy, adverse events, comparative effectiveness, surface under the cumulative ranking curve, Mini-Mental State Examination, CDR-SB, ADAS-Cog
- MeSH terms
- Network Meta-Analysis, Activities of Daily Living, Alzheimer Disease, Antibodies, Monoclonal, Humans, Randomized Controlled Trials as Topic, Cognitive Dysfunction, Antibodies, Monoclonal, Humanized
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