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Title: Trial of Solanezumab for Mild Dementia Due to Alzheimer's Disease.
Austin Authors: Honig, Lawrence S;Vellas, Bruno;Woodward, Michael M ;Boada, Mercè;Bullock, Roger;Borrie, Michael;Hager, Klaus;Andreasen, Niels;Scarpini, Elio;Liu-Seifert, Hong;Case, Michael;Dean, Robert A;Hake, Ann;Sundell, Karen;Poole Hoffmann, Vicki;Carlson, Christopher;Khanna, Rashna;Mintun, Mark;DeMattos, Ronald;Selzler, Katherine J;Siemers, Eric
Affiliation: Department of Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York
Gérontopôle, Centre Hospitalier Universitaire Toulouse, Unité Mixte de Recherche INSERM Unité 1027 Université Toulouse III-Paul Sabatier, Toulouse, France
Continuing Care Clinical Service Unit, Austin Health, Heidelberg, Victoria, Australia
University of Melbourne, Melbourne, Victoria, Australia
Fundació ACE, Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona
Kingshill Research Centre, Victoria Hospital, Swindon, United Kingdom
Division of Geriatric Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
Clinic for Medicine of the Elderly, Diakovere Henriettenstift, Hannover, Germany
Karolinska Institutet Alzheimer's Disease Research Center and Clinical Trial Unit, Geriatric Clinic, Karolinska University Hospital, Huddinge, Sweden
Department of Pathophysiology and Transplantation, Neurology Unit, Dino Ferrari Center, University of Milan, Fondazione Ca' Granda, Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Policlinico, Milan
Eli Lilly, Indianapolis, USA
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, USA
Avid Radiopharmaceuticals, Philadelphia, USA
Issue Date: 25-Jan-2018
Publication information: The New England journal of medicine 2018; 378(4): 321-330
Abstract: Alzheimer's disease is characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The humanized monoclonal antibody solanezumab was designed to increase the clearance from the brain of soluble Aβ, peptides that may lead to toxic effects in the synapses and precede the deposition of fibrillary amyloid. We conducted a double-blind, placebo-controlled, phase 3 trial involving patients with mild dementia due to Alzheimer's disease, defined as a Mini-Mental State Examination (MMSE) score of 20 to 26 (on a scale from 0 to 30, with higher scores indicating better cognition) and with amyloid deposition shown by means of florbetapir positron-emission tomography or Aβ1-42 measurements in cerebrospinal fluid. Patients were randomly assigned to receive solanezumab at a dose of 400 mg or placebo intravenously every 4 weeks for 76 weeks. The primary outcome was the change from baseline to week 80 in the score on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog14; scores range from 0 to 90, with higher scores indicating greater cognitive impairment). A total of 2129 patients were enrolled, of whom 1057 were assigned to receive solanezumab and 1072 to receive placebo. The mean change from baseline in the ADAS-cog14 score was 6.65 in the solanezumab group and 7.44 in the placebo group, with no significant between-group difference at week 80 (difference, -0.80; 95% confidence interval, -1.73 to 0.14; P=0.10). As a result of the failure to reach significance with regard to the primary outcome in the prespecified hierarchical analysis, the secondary outcomes were considered to be descriptive and are reported without significance testing. The change from baseline in the MMSE score was -3.17 in the solanezumab group and -3.66 in the placebo group. Adverse cerebral edema or effusion lesions that were observed on magnetic resonance imaging after randomization occurred in 1 patient in the solanezumab group and in 2 in the placebo group. Solanezumab at a dose of 400 mg administered every 4 weeks in patients with mild Alzheimer's disease did not significantly affect cognitive decline. (Funded by Eli Lilly; EXPEDITION3 number, NCT01900665 .).
DOI: 10.1056/NEJMoa1705971
PubMed URL: 29365294
Type: Journal Article
Appears in Collections:Journal articles

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