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TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease
Stephen Salloway, Elly Lee, Michelle Papka, Andrew Pain, Ena Oru, Margaret B. Ferguson, Hong Wang, Michael G. Case et al.. BJPsych Open, 2023-07-01
Topic: Drug trials: efficacy and safety
Aims To evaluate the potential superiority of donanemab vs. aducanumab on the percentage of participants with amyloid plaque clearance (≤24.1 Centiloids [CL]) at 6 months in patients with early symptomatic Alzheimer's disease (AD) in phase 3 TRAILBLAZER-ALZ-4 study. The amyloid cascade in AD involves the production and deposition of amyloid beta (Aβ) as an early and necessary event in the pathogenesis of AD. Methods Participants (n = 148) were randomized 1:1 to receive donanemab (700 mg IV Q4W [first 3 doses], then 1400 mg IV Q4W [subsequent doses]) or aducanumab (per USPI: 1 mg/kg IV Q4W [first 2 doses], 3 mg/kg IV Q4W [next 2 doses], 6 mg/kg IV Q4W [next 2 doses] and 10 mg/kg IV Q4W [subsequent doses]). Results Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]). Twenty-seven donanemab-treated and 28 aducanumab-treated participants defined as having intermediate tau. Upon assessment of florbetapir F18 PET scans (6 months), 37.9% donanemab-treated vs. 1.6% aducanumab-treated participants achieved amyloid clearance (p < 0.001). In the intermediate tau subpopulation, 38.5% donanemab-treated vs. 3.8% aducanumab-treated participants achieved amyloid clearance (p = 0.008). Percent change in brain amyloid levels were −65.2%±3.9% (baseline: 98.29 ± 27.83 CL) and −17.0%±4.0% (baseline: 102.40 ± 35.49 CL) in donanemab and aducanumab arms, respectively (p < 0.001). In the intermediate tau subpopulation, percent change in brain amyloid levels were −63.9%±7.4% (baseline: 104.97 ± 25.68 CL) and −25.4%±7.8% (baseline: 102.23 ± 28.13 CL) in donanemab and aducanumab arms, respectively (p ≤ 0.001). 62.0% of donanemab-treated and 66.7% of aducanumab-treated participants reported an adverse event (AE), there were no serious AEs due to ARIA in donanemab arm and 1.4% serious AEs (one event) due to ARIA were reported in aducanumab arm. Conclusion This study provides the first active comparator data on amyloid plaque clearance in patients with early symptomatic AD. Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months. Previously presented at the Clinical Trials on Alzheimer's Disease - 15th Conference, 2022.
Key findings
- Results Baseline demographics and characteristics were well-balanced across treatment arms (donanemab [N = 71], aducanumab [N = 69]).
- Significantly higher number of participants reached amyloid clearance and amyloid plaque reductions with donanemab vs. aducanumab at 6 months.
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Study details
- Study designclinical trial
- Participants148
- Effect size37.9%; 1.6%; 38.5%
- Evidence strengthHigh
How this study scored 62/100
Published in a peer-reviewed journal. Scored zero for study design because the record does not state it. 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 36 of the 58 points we could judge it on, which is 62 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (BJPsych Open) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “clinical trial”, which our rubric does not rank (not stated in the record — scored 0) |
| 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 | 2023 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 148 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 36 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 36 of the 58 points we could judge it on is 62 out of 100. |
| Total | 62 / 100 | — |
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APA 7th
Salloway, S., Lee, E., Papka, M., Pain, A., Oru, E., Ferguson, M. B., et al. (2023). TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease. BJPsych Open. https://doi.org/10.1192/bjo.2023.227
Vancouver
Salloway S, Lee E, Papka M, Pain A, Oru E, Ferguson MB, et al. TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease. BJPsych Open. 2023. doi:10.1192/bjo.2023.227.
BibTeX
@article{salloway2023-7521651f,
author = {Salloway, Stephen and Lee, Elly and Papka, Michelle and Pain, Andrew and Oru, Ena and Ferguson, Margaret B. and Wang, Hong and Case, Michael G. and others},
title = {{TRAILBLAZER-ALZ 4: Topline Study Results Directly Comparing Donanemab to Aducanumab on Amyloid Lowering in Early, Symptomatic Alzheimer's Disease}},
journal = {BJPsych Open},
year = {2023},
doi = {10.1192/bjo.2023.227},
url = {https://doi.org/10.1192/bjo.2023.227}
}