Home › Research › Treatments
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
Avgerinos KI, Ferrucci L, Kapogiannis D.. Ageing research reviews, 2021-04-05
Topic: Plasma and spinal-fluid biomarkers
Objective To investigate the effects of monoclonal antibodies against Aβ on cognition, function, amyloid PET and other biomarkers, as well as risk for amyloid-related imaging abnormalities (ARIA) and other adverse events, in Alzheimer's disease (AD). Methods Pubmed, Web of Science, ClinicalTrials.gov and gray literature were searched for phase III RCTs and random-effects meta-analyses were performed. Results Seventeen studies (12,585 patients) were included. Antibodies statistically improved the cognitive outcomes ADAS-Cog {SMD = -0.06 [95 % CI (-0.10; -0.02), I 2 = 0%]} and MMSE {SMD = 0.05 [95 % CI (0.01; 0.09), I 2 = 0%]} by small effect sizes, but did not improve the cognitive/functional measure CDR-SOB {SMD = -0.03 [95 % CI (-0.07; 0.01), I 2 = 18 %]}. Moreover, antibodies decreased amyloid PET SUVR {SMD = -1.02 [95 % CI (-1.70; -0.34), I 2 = 95 %]} and CSF p181-tau {SMD = -0.87 [95 % CI (-1.32; -0.43), I 2 = 89 %]} by large effect sizes. They also increased risk for ARIA {RR = 4.30 [95 % CI (2.39; 7.77), I 2 = 86 %]} by a large effect size. Antibody effects on reducing amyloid PET SUVR were correlated with their effects on improving ADAS-Cog (r = +0.68, p = 0.02). In subgroup analyses by individual drug, Aducanumab improved ADAS-Cog, CDR-SOB, ADCS-ADL by small effect sizes and decreased amyloid PET SUVR and CSF p181-tau by large effect sizes. Solanezumab improved ADAS-Cog and MMSE by small effect sizes, and increased (improved) CSF Aβ 1-40 levels by a moderate effect size. Bapineuzumab, Gantenerumab and Crenezumab did not improve any clinical outcomes. Bapineuzumab and Gantenerumab decreased CSF p181-tau by a small and large effect size, respectively. All drugs except Solanezumab increased ARIA risk. Conclusions In this meta-analysis of phase III trials in AD, we found that monoclonal antibodies against Aβ induced clinical improvements of small effect sizes, biomarker improvements of large effect sizes, and increases in risk for the hallmark adverse event, ARIA, by a large effect size, when all drugs were pooled together. Among individual drugs, Aducanumab produced the most favorable effects followed by Solanezumab. These findings provide moderate support for the continuous development of anti-Aβ monoclonal antibodies as a treatment for AD.
Key findings
- Results Seventeen studies (12,585 patients) were included.
- They also increased risk for ARIA {RR = 4.30 [95 % CI (2.39; 7.77), I 2 = 86 %]} by a large effect size.
- Conclusions In this meta-analysis of phase III trials in AD, we found that monoclonal antibodies against Aβ induced clinical improvements of small effect sizes, biomarker improvements of large effect sizes, and increases in risk for the hallmark adverse event, ARIA, by a large effect size, when all drugs were pooled together.
- These findings provide moderate support for the continuous development of anti-Aβ monoclonal antibodies as a treatment for AD.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designmeta-analysis
- Participants12,585
- Effect sizeRR = 4.30
- Evidence strengthHigh
How this study scored 84/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 49 of the 58 points we could judge it on, which is 84 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Ageing research reviews) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 4 / 4 | 12,585 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | A review of other studies — randomisation is not credited here |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33831607) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 49 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 49 of the 58 points we could judge it on is 84 out of 100. |
| Total | 84 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Free copy unknown: no free-copy check has an answer for this record yet. That does not mean it is paywalled.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Avgerinos, K. I., Ferrucci, L., & Kapogiannis, D. (2021). 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 research reviews. https://doi.org/10.1016/j.arr.2021.101339
Vancouver
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 research reviews. 2021. doi:10.1016/j.arr.2021.101339. PMID: 33831607.
BibTeX
@article{avgerinos2021-33831607,
author = {Avgerinos, K. I. and Ferrucci, L. and Kapogiannis, D.},
title = {{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}},
journal = {Ageing research reviews},
year = {2021},
doi = {10.1016/j.arr.2021.101339},
pmid = {33831607},
url = {https://doi.org/10.1016/j.arr.2021.101339}
}