Donanemab in Early Alzheimer's Disease.

Activities of Daily Living Administration, Intravenous Aged Alzheimer Disease / drug therapy Brain Edema / chemically induced Cognition / drug effects Disease Progression Double-Blind Method Epitopes Female Humans Male Mental Status and Dementia Tests Plaque, Amyloid / drug therapy Pyrrolidonecarboxylic Acid / antagonists & inhibitors Severity of Illness Index

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
06 05 2021
Historique:
pubmed: 16 3 2021
medline: 18 5 2021
entrez: 15 3 2021
Statut: ppublish

Résumé

A hallmark of Alzheimer's disease is the accumulation of amyloid-β (Aβ) peptide. Donanemab, an antibody that targets a modified form of deposited Aβ, is being investigated for the treatment of early Alzheimer's disease. We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer's disease who had tau and amyloid deposition on positron-emission tomography (PET). Patients were randomly assigned in a 1:1 ratio to receive donanemab (700 mg for the first three doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The primary outcome was the change from baseline in the score on the Integrated Alzheimer's Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks. Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was -6.86 with donanemab and -10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P = 0.04). The results for most secondary outcomes showed no substantial difference. At 76 weeks, the reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred with donanemab. In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer's disease. (Funded by Eli Lilly; TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403.).

Sections du résumé

BACKGROUND
A hallmark of Alzheimer's disease is the accumulation of amyloid-β (Aβ) peptide. Donanemab, an antibody that targets a modified form of deposited Aβ, is being investigated for the treatment of early Alzheimer's disease.
METHODS
We conducted a phase 2 trial of donanemab in patients with early symptomatic Alzheimer's disease who had tau and amyloid deposition on positron-emission tomography (PET). Patients were randomly assigned in a 1:1 ratio to receive donanemab (700 mg for the first three doses and 1400 mg thereafter) or placebo intravenously every 4 weeks for up to 72 weeks. The primary outcome was the change from baseline in the score on the Integrated Alzheimer's Disease Rating Scale (iADRS; range, 0 to 144, with lower scores indicating greater cognitive and functional impairment) at 76 weeks. Secondary outcomes included the change in scores on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), the 13-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog
RESULTS
A total of 257 patients were enrolled; 131 were assigned to receive donanemab and 126 to receive placebo. The baseline iADRS score was 106 in both groups. The change from baseline in the iADRS score at 76 weeks was -6.86 with donanemab and -10.06 with placebo (difference, 3.20; 95% confidence interval, 0.12 to 6.27; P = 0.04). The results for most secondary outcomes showed no substantial difference. At 76 weeks, the reductions in the amyloid plaque level and the global tau load were 85.06 centiloids and 0.01 greater, respectively, with donanemab than with placebo. Amyloid-related cerebral edema or effusions (mostly asymptomatic) occurred with donanemab.
CONCLUSIONS
In patients with early Alzheimer's disease, donanemab resulted in a better composite score for cognition and for the ability to perform activities of daily living than placebo at 76 weeks, although results for secondary outcomes were mixed. Longer and larger trials are necessary to study the efficacy and safety of donanemab in Alzheimer's disease. (Funded by Eli Lilly; TRAILBLAZER-ALZ ClinicalTrials.gov number, NCT03367403.).

Identifiants

DOI: 10.1056/NEJMoa2100708 PMID: 33720637
pubmed: 33720637
doi: 10.1056/NEJMoa2100708
doi:

Substances chimiques

Epitopes 0
Pyrrolidonecarboxylic Acid SZB83O1W42

Banques de données

ClinicalTrials.gov
['NCT03367403']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1691-1704

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Mark A Mintun (MA)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Albert C Lo (AC)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Cynthia Duggan Evans (C)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Alette M Wessels (AM)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Paul A Ardayfio (PA)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Scott W Andersen (SW)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Sergey Shcherbinin (S)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

JonDavid Sparks (J)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

John R Sims (JR)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Miroslaw Brys (M)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Liana G Apostolova (LG)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Stephen P Salloway (SP)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

Daniel M Skovronsky (DM)

From Eli Lilly (M.A.M., A.C.L., C.D.E., A.M.W., P.A.A., S.W.A., S.S., J.S., J.R.S., M.B., D.M.S.) and the Departments of Neurology, of Radiology and Imaging Sciences, and of Medical and Molecular Genetics and the Indiana Alzheimer Disease Center, Indiana University School of Medicine (L.G.A.) - both in Indianapolis; and the Departments of Psychiatry and Human Behavior and of Neurology, Butler Hospital, Warren Alpert Medical School of Brown University, Providence, RI (S.P.S.).

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Classifications MeSH

questionsmedicales.fr › Établissements, main d'oeuvre et services de soins de santé › Services de santé › Réadaptation › Activités de la vie quotidienne › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Voies d'administration de substances chimiques et des médicaments › Administration par voie intraveineuse › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Troubles mentaux › Troubles neurocognitifs › Démence › Maladie d'Alzheimer › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Maladies du système nerveux › Maladies du système nerveux central › Encéphalopathies › Oedème cérébral › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Phénomènes psychologiques › Processus mentaux › Cognition › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Disciplines et activités comportementales › Tests psychologiques › Tests neuropsychologiques › Tests de l'état mental et de la démence › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Plaque amyloïde › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Acides aminés cycliques › Imino-acides › Acide pidolique › Donanemab in Early Alzheimer's Disease.
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Enquêtes et questionnaires › Enquêtes de santé › Indicateurs d'état de santé › Acuité des besoins du patient › Indice de gravité de la maladie › Donanemab in Early Alzheimer's Disease.