| Title: |
Amyloid-Related Imaging Abnormalities (ARIA) in Clinical Trials of Gantenerumab in Early Alzheimer Disease |
| Authors: |
Salloway, Stephen; Wojtowicz, Jakub; Voyle, Nicola; Lane, Christopher A.; Klein, Gregory; Lyons, Marco; Rossomanno, Simona; Mazzo, Francesca; Bullain, Szofia; Barkhof, Frederik; Bittner, Tobias; Schneider, Andres; Grundman, Michael; Aldea, Roxana; Boada, Mercè; Smith, Janice; Doody, Rachelle; Filippi, M |
| Contributors: |
Salloway, Stephen; Wojtowicz, Jakub; Voyle, Nicola; Lane, Christopher A.; Klein, Gregory; Lyons, Marco; Rossomanno, Simona; Mazzo, Francesca; Bullain, Szofia; Barkhof, Frederik; Bittner, Tobia; Schneider, Andre; Grundman, Michael; Aldea, Roxana; Boada, Mercè; Smith, Janice; Doody, Rachelle; Filippi, M |
| Publisher Information: |
American Medical Association |
| Publication Year: |
2025 |
| Description: |
Importance: Data from 2 phase 3 studies of gantenerumab, GRADUATE I/II, and their open-label extensions represent a resource to further characterize amyloid-related imaging abnormalities (ARIA), including long-term sequelae. Objectives: To describe the characteristics of ARIA and risk factors and clinical consequences of ARIA-edema (ARIA-E). Design, Setting, and Participants: Secondary data collection from the GRADUATE I/II phase 3 randomized, double-blind, placebo-controlled, 116-week parallel-group studies and their open-label extensions, including PostGraduate, with up to 210 (mean, 125) weeks of total gantenerumab treatment were conducted between 2018 and 2023. The study included multicenter trials at 288 sites across 30 countries. GRADUATE I/II enrolled 985 and 980 participants, respectively, with early symptomatic Alzheimer disease (AD) and amyloid-beta (Aβ) pathology who were aged 50 to 90 years. PostGraduate enrolled 1382 participants (671 previously randomized to gantenerumab). Data were analyzed from November 2, 2022, to October 10, 2023. Interventions: GRADUATE I/II participants were randomized 1:1 to gantenerumab or placebo. Nine-month uptitration was used to mitigate ARIA risk. Main outcomes and measures: Postbaseline safety monitoring, including brain magnetic resonance imaging (MRI) findings, and adverse events and cognitive assessments. Results: The safety-evaluable MRI population of GRADUATE I/II comprised 1939 participants (mean age, 71.7 years; 1105 female [57.0%]). Severity of AD-related Aβ neuropathology (lower cerebrospinal fluid [CSF] Aβ42, hazard ratio [HR] for CSF Aβ42: 0.4; 95% CI, 0.2-0.7) and comorbid cerebrovascular pathology (Fazekas score: HR, 1.6; 95% CI, 1.3-2.0; total superficial siderosis count: HR, 1.9; 95% CI, 1.3-2.6; total microhemorrhage count: HR, 1.3; 95% CI, 1.0-1.5) may be important baseline risk factors for ARIA-E, in addition to apolipoprotein E (APOE) ε4 status (APOE ε4 heterozygous carrier: HR, 2.0; 95% CI, 1.4-2.8 and APOE ε4 homozygous carrier: HR, 4.7; 95% CI, ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39556389; info:eu-repo/semantics/altIdentifier/wos/WOS:001361840200002; volume:82; issue:1; firstpage:19; lastpage:29; numberofpages:11; journal:JAMA NEUROLOGY; https://hdl.handle.net/20.500.11768/179596; https://jamanetwork.com/journals/jamaneurology/fullarticle/2826606 |
| DOI: |
10.1001/jamaneurol.2024.3937 |
| Availability: |
https://hdl.handle.net/20.500.11768/179596; https://doi.org/10.1001/jamaneurol.2024.3937; https://jamanetwork.com/journals/jamaneurology/fullarticle/2826606 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Creative commons ; license uri:http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.CAE8533C |
| Database: |
BASE |