Aducanumab: Appropriate Use Recommendations Update

Cummings, Jeffrey L.; Rabinovici, Gil D.; Atri, Alireza; Aisen, Paul S.; Apostolova, Liana G.; Hendrix, Suzanne; Sabbagh, Marwan N.; Selkoe, Dennis J.; Weiner, Michael W.; Salloway, Stephen

doi:10.14283/jpad.2022.34

Cited by 120 publications

(179 citation statements)

References 43 publications

Supporting

Mentioning

177

Contrasting

Unclassified

Order By: Relevance

“…However, the Centers for Medicare & Medicaid Services issued a decision to cover FDA-approved monoclonal antibody therapy solely under coverage with evidence development. This requires new randomized placebo-controlled therapeutic trials testing the efficacy of aducanumab showing clinical benefit to be developed before the CMS ruling in favor of clinical coverage of aducanumab 75,76 …”

Section: Treatment and Managementmentioning

confidence: 99%

Atypical Alzheimer Disease Variants

Polsinelli¹,

Apostolova²

2022

CONTINUUM: Lifelong Learning in Neurology

View full text Add to dashboard Cite

PURPOSE OF REVIEWThis article discusses the clinical, neuroimaging, and biomarker profiles of sporadic atypical Alzheimer disease (AD) variants, including early-onset AD, posterior cortical atrophy, logopenic variant primary progressive aphasia, dysexecutive variant and behavioral variant AD, and corticobasal syndrome.RECENT FINDINGSSignificant advances are being made in the recognition and characterization of the syndromically diverse AD variants. These variants are identified by the predominant cognitive and clinical features: early-onset amnestic syndrome, aphasia, visuospatial impairments, dysexecutive and behavioral disturbance, or motor symptoms. Although understanding of regional susceptibility to disease remains in its infancy, visualizing amyloid and tau pathology in vivo and CSF examination of amyloid-β and tau proteins are particularly useful in atypical AD, which can be otherwise prone to misdiagnosis. Large-scale research efforts, such as LEADS (the Longitudinal Early-Onset Alzheimer Disease Study), are currently ongoing and will continue to shed light on our understanding of these diverse presentations.SUMMARYUnderstanding the clinical, neuroimaging, and biomarker profiles of the heterogeneous group of atypical AD syndromes improves diagnostic accuracy in patients who are at increased risk of misdiagnosis. Earlier accurate identification facilitates access to important interventions, social services and disability assistance, and crucial patient and family education.

show abstract

Section: Treatment and Managementmentioning

confidence: 99%

Atypical Alzheimer Disease Variants

Polsinelli¹,

Apostolova²

2022

CONTINUUM: Lifelong Learning in Neurology

View full text Add to dashboard Cite

show abstract

“…Serial measurements of p-tau 181, p-tau 217, and Aβ 42/40 have been used as monitoring biomarkers and demonstrate changes that occur in concert with plaque reduction induced by MABs. MRI is used as a monitoring biomarker and a safety biomarker to detect amyloid-related imaging abnormalities (ARIAs) in patients receiving MABs [ 31 , 32 ].…”

Section: Biomarker Definition and Classificationmentioning

confidence: 99%

“…This is particularly likely during the initial phases of treatment. MRIs are scheduled at routine intervals in the first months of therapy, and additional imaging is performed if symptoms suggestive of ARIA occur [ 31 , 32 ].…”

Section: Biomarker Definition and Classificationmentioning

confidence: 99%

“…Aducanumab has been studied only in patients with early AD, with amyloidosis confirmed by amyloid PET. The Appropriate Use Recommendations specify that the establishment of amyloid abnormalities through amyloid PET or CSF amyloid measures is required for the use of aducanumab since it is only in this population that the efficacy and safety of this agent have been studied [ 31 , 32 ]. Other MABs may be administered to restricted populations (early AD with positive amyloid studies) and may have similar requirements for safe and effective use.…”

Section: Biomarkers For Use In Clinical Carementioning

confidence: 99%

See 1 more Smart Citation

Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation

Cummings

Kinney

2022

Medicina

View full text Add to dashboard Cite

Background and Objectives: The US Food and Drug Administration (FDA) defines a biomarker as a characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or responses to an exposure or intervention. Biomarkers may be used in clinical care or as drug development tools (DDTs) in clinical trials. The goal of this review and perspective is to provide insight into the regulatory guidance for the use of biomarkers in clinical trials and clinical care. Materials and Methods: We reviewed FDA guidances relevant to biomarker use in clinical trials and their transition to use in clinical care. We identified instructive examples of these biomarkers in Alzheimer’s disease (AD) drug development and their application in clinical practice. Results: For use in clinical trials, biomarkers must have a defined context of use (COU) as a risk/susceptibility, diagnostic, monitoring, predictive, prognostic, pharmacodynamic, or safety biomarker. A four-stage process defines the pathway to establish the regulatory acceptance of the COU for a biomarker including submission of a letter of intent, description of the qualification plan, submission of a full qualification package, and acceptance through a qualification recommendation. Biomarkers used in clinical care may be companion biomarkers, in vitro diagnostic devices (IVDs), or laboratory developed tests (LDTs). A five-phase biomarker development process has been proposed to structure the biomarker development process. Conclusions: Biomarkers are increasingly important in drug development and clinical care. Adherence to regulatory guidance for biomarkers used in clinical trials and patient care is required to advance these important drug development and clinical tools.

show abstract

“…Memantine, an N-methyl-D-aspartate (NMDA) receptor blocker, one of the most frequently prescribed medications in the United States, is administered alone or in combination therapy in moderate-to-severe AD patients [ 22 ]. Very recently, the first Food and Drug Administration (FDA)-approved Aβ-directed monoclonal antibody was introduced as a therapeutic option for AD patients [ 23 ], with data from the open-world still to be published.…”

Section: Introductionmentioning

confidence: 99%

The “Cerebrospinal Fluid Sink Therapeutic Strategy” in Alzheimer’s Disease—From Theory to Design of Applied Systems

2022

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a global health problem, with incidence and prevalence considered to increase during the next decades. However, no currently available effective treatment exists despite numerous clinical trials in progress. Moreover, although many hypotheses are accepted regarding the pathophysiological mechanisms of AD onset and evolution, there are still many unknowns about the disorder. A relatively new approach, based on the amyloid-beta dynamics among different biological compartments, is currently intensely discussed, as it seems to offer a promising solution with significant therapeutic impact. Known as the “cerebrospinal-fluid-sink therapeutic strategy”, part of the “three-sink therapeutic strategy”, this theoretical model focuses on the dynamics of amyloid-beta among the three main liquid compartments of the human body, namely blood, cerebrospinal fluid, and the (brain) interstitial fluid. In this context, this article aims to describe in detail the abovementioned hypothesis, by reviewing in the first part the most relevant anatomical and physiological aspects of amyloid-beta dynamics. Subsequently, explored therapeutic strategies based on the clearance of amyloid-beta from the cerebrospinal fluid level are presented, additionally highlighting their limitations. Finally, the originality and novelty of this work rely on the research experience of the authors, who focus on implantable devices and their utility in AD treatment.

show abstract

Aducanumab: Appropriate Use Recommendations Update

Cited by 120 publications

References 43 publications

Atypical Alzheimer Disease Variants

Atypical Alzheimer Disease Variants

Biomarkers for Alzheimer’s Disease: Context of Use, Qualification, and Roadmap for Clinical Implementation

The “Cerebrospinal Fluid Sink Therapeutic Strategy” in Alzheimer’s Disease—From Theory to Design of Applied Systems

Contact Info

Product

Resources

About