Evidence map›Paper›PMID 40172303›Full record

Trial reportAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction.

Hong Wang, Emel Serap Monkul Nery, Paul Ardayfio, Rashna Khanna, Diana Otero Svaldi, Ivelina Gueorguieva, Sergey Shcherbinin, Scott W Andersen, Paula M Hauck, Staci E Engle and 7 more

Erratum issued Registry-linked trialAbstract readRandomized Controlled TrialMulticenter StudyClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05738486 (Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease), which is not on this map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05738486 phase3active not recruitingnot on this map

Investigating the Effect of Different Donanemab Dosing Regimens on ARIA-E and Amyloid Lowering in Adults With Early Symptomatic Alzheimer's Disease

TypeinterventionalSponsorEli Lilly and CompanyRan2023 to 2027Enrolled1,175ConditionsAlzheimer's Disease, Dementia, Brain Diseases, Central Nervous System DiseasesArmsDonanemab, Placebo, Dexamethasone
3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Trial
  3. Donanemab exposure-response in early symptomatic Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  4. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Trial
  5. Article
  6. Review
  7. Further data to address the Alzheimer's coverage with evidence development questions.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  8. Donanemab for early Alzheimer disease.Australian prescriber · 2026
    Review
  9. APOE-guided lecanemab dosing dissociates ARIA-E from ARIA-H: The K-ROAD study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Observational
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Ex vivo comparison of ACU193 and lecanemab reveals binding differences in mouse brain.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Hong WangEli Lilly and Company, Indianapolis, Indiana, USA.
Emel Serap Monkul NeryEli Lilly and Company, Indianapolis, Indiana, USA.
Paul ArdayfioEli Lilly and Company, Indianapolis, Indiana, USA.
Rashna KhannaEli Lilly and Company, Indianapolis, Indiana, USA.
Diana Otero SvaldiEli Lilly and Company, Indianapolis, Indiana, USA.
Ivelina GueorguievaEli Lilly and Company, Indianapolis, Indiana, USA.
Sergey ShcherbininEli Lilly and Company, Indianapolis, Indiana, USA.
Scott W AndersenEli Lilly and Company, Indianapolis, Indiana, USA.
Paula M HauckEli Lilly and Company, Indianapolis, Indiana, USA.
Staci E EngleEli Lilly and Company, Indianapolis, Indiana, USA.
Dawn A BrooksEli Lilly and Company, Indianapolis, Indiana, USA.
Emily C CollinsEli Lilly and Company, Indianapolis, Indiana, USA.
Nick C FoxDementia Research Centre, Department of Neurodegenerative Disease, and the UK Dementia Research Institute, UCL Queen Square Institute of Neurology, London, UK.
Steven M GreenbergDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Stephen SallowayButler Hospital, Providence, Rhode Island, USA.
Mark A MintunEli Lilly and Company, Indianapolis, Indiana, USA.
John R SimsEli Lilly and Company, Indianapolis, Indiana, USA.

Funding

Eli Lilly and Company
6 · The paper itself

Abstract

introductionTRAILBLAZER-ALZ 6 (NCT05738486) is a multicenter, double-blind, ongoing phase 3b study in early symptomatic Alzheimer's disease.

methodsParticipants (n = 843) were randomized 1:1:1:1 (standard + three alternative donanemab dosing arms). Primary outcome was relative risk reduction (RRR) of amyloid-related imaging abnormalities with edema/effusions (ARIA-E) at 24 weeks assessed with Bayesian logistic regression. Amyloid plaque levels by positron emission tomography and serum donanemab pharmacokinetics were measured.

resultsARIA-E frequencies for standard, modified titration, dose skipping, and C DISCUSSION: Gradual up-titration of dose significantly reduced ARIA-E risk while demonstrating comparable pharmacokinetics/pharmacodynamics compared to standard dosing. HIGHLIGHTS: In TRAILBLAZER-ALZ 6, the amyloid-related imaging abnormalities-edema/effusions (ARIA-E) frequency was 13.7% in the modified titration arm compared to 23.7% in the standard arm at week 24. The modified titration arm met the primary endpoint of ARIA-E relative risk reduction at 24 weeks versus the standard arm. The modified titration versus standard arm at week 24 had comparable non-ARIA-E related safety profile, amyloid reduction, plasma phosphorylated tau217 reduction, cumulative exposure, and pharmacokinetics. Data at week 52 were consistent with week 24 results.

Indexed as

Alzheimer DiseasePlaque, AmyloidAgedAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedDouble-Blind MethodFemaleHumansMaleMiddle AgedPositron-Emission TomographyAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizeddonanemabAlzheimer's diseaseamyloidamyloid‐related imaging abnormalitiesdonanemabphosphorylated tau217titration

Identifiers

PMID40172303
PMCPMC11963282

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.