title: Central Review of Amyloid-Related Imaging Abnormalities in Two Phase III Clinical Trials of Bapineuzumab in Mild-To-Moderate Alzheimer's Disease Patients.
abstract: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]).
  
  
  
  To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE ɛ4 allele carriers or noncarriers).
  
  
  
  Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE ɛ4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described.
  
  
  
  In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE ɛ4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10 mm (cerebral microhemorrhages) was higher in active groups versus placebo.
  
  
  
  ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study.
authors.affiliation: Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA.
authors.forename: Nzeera
authors.initials: N
authors.lastname: Ketter
authors.affiliation: Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA.
authors.forename: H Robert
authors.initials: HR
authors.lastname: Brashear
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bogert
authors.affiliation: Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA.
authors.forename: Jianing
authors.initials: J
authors.lastname: Di
authors.affiliation: BioClinica Inc. (formerly Synarc), Newtown, PA, USA.
authors.forename: Yves
authors.initials: Y
authors.lastname: Miaux
authors.affiliation: BioClinica Inc. (formerly Synarc), Newtown, PA, USA.
authors.forename: Achim
authors.initials: A
authors.lastname: Gass
authors.affiliation: BioClinica Inc. (formerly Synarc), Newtown, PA, USA.
authors.forename: Derk D
authors.initials: DD
authors.lastname: Purcell
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Janssen Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, CA, USA.
authors.forename: H Michael
authors.initials: HM
authors.lastname: Arrighi
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics; D000682:Amyloid / Q000187:drug effects; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D006579:Heterozygote; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index; D066127:White Matter / Q000000981:diagnostic imaging / Q000187:drug effects
chemical_list: D000682:Amyloid; D061067:Antibodies, Monoclonal, Humanized; D053327:Apolipoprotein E4; D007155:Immunologic Factors; C545458:bapineuzumab
keywords: Alzheimer’s disease; NCT00575055 (Bapineuzumab-302); bapineuzumab; brain amyloid-related imaging abnormality; magnetic resonance imaging
   Registration: NCT00574132 (Bapineuzumab-301)