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Abstract
Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using 11C-Pittsburgh compound B (11C-PiB)-PET.
Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks. PET substudies assessed change in brain fibrillar Aβ over 71 weeks using an 11C-PiB-PET standardized uptake value ratio (SUVr) global cortical average (GCA) comprising the average SUVr from 5 cortical regions of interest with cerebellar gray matter as the reference region.
Results: A total of 115 carriers and 39 noncarriers were analyzed. The difference (δ) in mean baseline to 71 week change in 11C-PiB-PET GCA between bapineuzumab and placebo was significant in carriers (0.5 mg/kg vs placebo δ = −0.101; p = 0.004) and in pooled analyses of both carriers and noncarriers (0.5 mg/kg vs placebo δ = −0.068; p = 0.027; 1.0 mg/kg vs placebo δ = −0.133; p = 0.028) but not in the noncarrier trial separately. Analyses by individual region of interest and in mild disease yielded findings similar to the main trial results.
Conclusions: The 11C-PiB-PET imaging results demonstrated reduction of fibrillar Aβ accumulation in patients with Alzheimer disease treated with bapineuzumab; however, as no clinical benefit was observed, the findings are consistent with the hypotheses that bapineuzumab may not have been initiated early enough in the disease course, the doses were insufficient, or the most critical Aβ species were inadequately targeted.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ARIA=
- amyloid-related imaging abnormalities;
- GCA=
- global cortical average;
- MMSE=
- Mini-Mental State Examination;
- NINCDS-ADRDA=
- National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association;
- PiB=
- Pittsburgh compound B;
- ROI=
- region of interest;
- SUVr=
- standardized uptake value ratio
Footnotes
Bapineuzumab Study 301 and 302 study investigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
All authors contributed equally to this work.
Supplemental data at Neurology.org
- Received November 25, 2014.
- Accepted in final form April 7, 2015.
- © 2015 American Academy of Neurology
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