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Donanemab for early symptomatic AD in the UK-indicated population: safety and efficacy in those who are non-carriers or heterozygous for APOE ε4
Brookfield N, Hauck PM, Doty EG, Zimmer JA, Yang F, Chen YF, Ardayfio P, Khanna R et al.. Neurodegenerative disease management, 2026-08-26
Topic: Risk, prevention and care in population studies
Background Licensing of donanemab in the United Kingdom (UK) for the treatment of early symptomatic Alzheimer's disease is limited to adults who are Apolipoprotein E (APOE) ε4 non-carriers or heterozygotes. Aim To assess safety and efficacy of donanemab in the UK-indicated population. Methods Post-hoc analysis of APOE ε4 non-carriers or heterozygotes from a pooled TRAILBLAZER-ALZ and TRAILBLAZER-ALZ 2 population and the TRAILBLAZER-ALZ 2 population assessed safety and efficacy, respectively. Results By 76 weeks, 13/825 (1.6%) and 170/816 (20.8%) participants in the placebo and donanemab arms experienced amyloid-related imaging abnormalities (ARIA)-edema/effusion, 96/825 (11.6%) and 218/816 (26.7%) participants experienced ARIA-microhemorrhages/superficial siderosis and 3/825 (0.4%) and 67/816 (8.2%) participants experienced infusion-related reactions, respectively. Donanemab significantly slowed disease progression versus placebo across multiple clinical scales, including a 40.3% ( p < 0.0001) lower risk of progression to the next stage as measured by the Clinical Dementia Rating-Global score. Amyloid clearance occurred in 80.8% of donanemab-treated participants. Conclusions In the UK-indicated population, excluding APOE ε4 homozygotes reduced, but did not eliminate, ARIA risk with donanemab. Treatment slowed disease progression and reduced brain amyloid plaque by 76 weeks. Therefore, donanemab treatment requires structured risk-benefit discussion and appropriate monitoring. Clinical trial registration ClinicalTrials.gov, NCT03367403, https://clinicaltrials.gov/study/NCT03367403 (TRAILBLAZER-ALZ) and NCT04437511, https://clinicaltrials.gov/study/NCT04437511 (TRAILBLAZER-ALZ 2).
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APA 7th
Brookfield, N., Hauck, P. M., Doty, E. G., Zimmer, J. A., Yang, F., Chen, Y. F., et al. (2026). Donanemab for early symptomatic AD in the UK-indicated population: safety and efficacy in those who are non-carriers or heterozygous for APOE ε4. Neurodegenerative disease management. https://doi.org/10.1080/17582024.2026.2723524
Vancouver
Brookfield N, Hauck PM, Doty EG, Zimmer JA, Yang F, Chen YF, et al. Donanemab for early symptomatic AD in the UK-indicated population: safety and efficacy in those who are non-carriers or heterozygous for APOE ε4. Neurodegenerative disease management. 2026. doi:10.1080/17582024.2026.2723524. PMID: 42644303.
BibTeX
@article{brookfield2026-42644303,
author = {Brookfield, N. and Hauck, P. M. and Doty, E. G. and Zimmer, J. A. and Yang, F. and Chen, Y. F. and Ardayfio, P. and Khanna, R. and others},
title = {{Donanemab for early symptomatic AD in the UK-indicated population: safety and efficacy in those who are non-carriers or heterozygous for APOE ε4}},
journal = {Neurodegenerative disease management},
year = {2026},
doi = {10.1080/17582024.2026.2723524},
pmid = {42644303},
url = {https://doi.org/10.1080/17582024.2026.2723524}
}
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Key findings
- Results By 76 weeks, 13/825 (1.6%) and 170/816 (20.8%) participants in the placebo and donanemab arms experienced amyloid-related imaging abnormalities (ARIA)-edema/effusion, 96/825 (11.6%) and 218/816 (26.7%) participants experienced ARIA-microhemorrhages/superficial siderosis and 3/825 (0.4%) and 67/816 (8.2%) participants experienced infusion-related reactions, respectively.
- Donanemab significantly slowed disease progression versus placebo across multiple clinical scales, including a 40.3% ( p < 0.0001) lower risk of progression to the next stage as measured by the Clinical Dementia Rating-Global score.
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Study details
- Study designpost-hoc analysis
- Effect size1.6%; 20.8%; 11.6%
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded 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 27 of the 58 points we could judge it on, which is 47 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurodegenerative disease management) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | Design recorded as “post-hoc analysis”, which our rubric does not rank (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| 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 42644303) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 27 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 27 of the 58 points we could judge it on is 47 out of 100. |
| Total | 47 / 100 | — |
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