Symptomatic amyloid‐related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab

VandeVrede, Lawren; Gibbs, Daniel M.; Koestler, Mary; Joie, Renaud La; Ljubenkov, Peter A.; Provost, Karine; Soleimani‐Meigooni, David N.; Strom, Amelia; Tsoy, Elena; Rabinovici, Gil D.; Boxer, Adam L.

doi:10.1002/dad2.12101

Cited by 42 publications

(39 citation statements)

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“…He was treated with corticosteroids and experienced a decrease in radiographic severity of ARIA-E and resolution of symptoms over the course of 6 months. 23 More real-world data on the treatment and management of ARIA, outside of the clinical trial protocols, are required to assess which medications may be effective in treating symptomatic patients with ARIA.…”

Section: Discussionmentioning

confidence: 99%

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

et al. 2022

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Key Points Question What are the characteristics of amyloid-related imaging abnormalities (ARIA) during aducanumab treatment in individuals with early Alzheimer disease? Findings In an integrated safety data set of 2 phase 3 clinical trials (EMERGE and ENGAGE) including 3285 participants, 425 patients (41.3%) in the combined 10 mg/kg aducanumab group (n = 1029) experienced ARIA; ARIA-edema occurred in 362 patients (35.2%), and 94 of these patients (26.0%) experienced associated symptoms (eg, headache, confusion, dizziness, and nausea). ARIA-microhemorrhage and ARIA–superficial siderosis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively. Meaning Amyloid-related imaging abnormalities occurred in approximately 40% of participants in the phase 3 studies of aducanumab, and approximately one-quarter of these patients experienced symptoms.

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Section: Discussionmentioning

confidence: 99%

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

et al. 2022

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“…The effects of ARIA have been dealt with for passive immunisation by titrating the dosage, pausing then re-starting dosing or withdrawing therapy altogether ( Sperling et al, 2011 ; Salloway et al, 2014 ). Risk of ARIA is increased with higher Aβ load, degree of CAA, APOE4 status and dose of immunotherapy ( Sperling et al, 2011 ; VandeVrede et al, 2020 ). The risks, causes and effects of immunotherapy induced ARIA and recommendations for future clinical trials have been discussed in detail by the Alzheimer’s association research round table workgroup ( Sperling et al, 2011 ).…”

Section: Amyloid Beta Targeted Immunotherapymentioning

confidence: 99%

Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials

Nimmo¹,

Kelly²,

Verma³

et al. 2021

Front. Neurosci.

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Alzheimer’s disease and Lewy body diseases are the most common causes of neurodegeneration and dementia. Amyloid-beta (Aβ) and alpha-synuclein (αSyn) are two key proteins involved in the pathogenesis of these neurodegenerative diseases. Immunotherapy aims to reduce the harmful effects of protein accumulation by neutralising toxic species and facilitating their removal. The results of the first immunisation trial against Aβ led to a small percentage of meningoencephalitis cases which revolutionised vaccine design, causing a shift in the field of immunotherapy from active to passive immunisation. While the vast majority of immunotherapies have been developed for Aβ and tested in Alzheimer’s disease, the field has progressed to targeting other proteins including αSyn. Despite showing some remarkable results in animal models, immunotherapies have largely failed final stages of clinical trials to date, with the exception of Aducanumab recently licenced in the US by the FDA. Neuropathological findings translate quite effectively from animal models to human trials, however, cognitive and functional outcome measures do not. The apparent lack of translation of experimental studies to clinical trials suggests that we are not obtaining a full representation of the effects of immunotherapies from animal studies. Here we provide a background understanding to the key concepts and challenges involved in therapeutic design. This review further provides a comprehensive comparison between experimental and clinical studies in Aβ and αSyn immunotherapy and aims to determine the possible reasons for the disconnection in their outcomes.

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“…Figure 4 represents the number of participants who experienced ARIA-E in EMERGE and ENGAGE, stratified by APOEε4 carrier status compared to placebo. Furthermore, homozygous carriers may be predisposed to more frequent and severe ARIA than those who carry only one copy of the allele [ 58 ]. Although genotype testing is currently not indicated as part of the pre-treatment procedure, clinicians must carefully assess the risk-benefit balance.…”

Section: Aducanumab In Low- and Middle-income Countriesmentioning

confidence: 99%

Is Aducanumab for LMICs? Promises and Challenges

2021

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Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries (LMICs), and the debilitating effects of this disease exerts burdens on patients and caregivers in addition to the significant economic strains many nations bear. While the advantages of a disease-modifying therapy are clear in delaying the progression of disease to improve patient outcomes, aducanumab’s approval by the U.S. FDA was met with controversy for a plethora of reasons. This paper will provide precursory insights into aducanumab’s role, appropriateness, and cost-effectiveness in low- and middle-income countries. We extend some of the controversies associated with aducanumab, including the contradicting evidence from the two trials (EMERGE and ENGAGE) and the resources required to deliver the treatment safely and effectively to patients, among other key considerations.

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Symptomatic amyloid‐related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab

Cited by 42 publications

References 10 publications

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

Amyloid-Related Imaging Abnormalities in 2 Phase 3 Studies Evaluating Aducanumab in Patients With Early Alzheimer Disease

Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials

Is Aducanumab for LMICs? Promises and Challenges

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