Changes in Brain Volume with Bapineuzumab in Mild to Moderate Alzheimer’s Disease

Article type: Research Article

Authors: Novak, Gerald^{a; *} | Fox, Nick^b | Clegg, Shona^b | Nielsen, Casper^b | Einstein, Steven^a | Lu, Yuan^c | Tudor, Iulia Cristina^d | Gregg, Keith^e | Di, Jianing^f | Collins, Peter^g | Wyman, Bradley T.^h | Yuen, Eric^e | Grundman, Michaelⁱ | Brashear, H. Robert^j | Liu, Enchi^f

Affiliations: [a] Janssen Research and Development, Titusville, NJ, USA | [b] Dementia Research Centre, University College London Institute of Neurology, London, UK | [c] Jazz Pharmaceuticals, Palo Alto, CA, USA | [d] Medivation, Inc., San Francisco, CA, USA | [e] Janssen Alzheimer Immunotherapy, South San Francisco, CA, USA | [f] Janssen Research and Development, San Diego, CA, USA | [g] BioMarin, Novato, CA, USA | [h] Pfizer Inc, Groton, CT, USA | [i] Global R&D Partners, LLC, San Diego, CA, USA | [j] Janssen Research and Development, Fremont, CA, USA

Correspondence: [*] Correspondence to: Gerald Novak, MD, Janssen Research and Development, 1125 Trenton-Harbourton Road, Titusville, NJ 08560, USA. Tel.: +1 609 730 4416; Fax: +1 609 730 2069; E-mail: Gnovak1@its.jnj.com

Abstract: Background:Bapineuzumab, an anti-amyloid-β monoclonal antibody, was evaluated in two placebo-controlled trials in APOE*ɛ4 carriers and noncarriers, respectively, with Alzheimer’s disease. Objectives:A volumetric magnetic resonance imaging substudy was performed to determine if bapineuzumab altered brain volume rate of change. Methods:Bapineuzumab dosages included 0.5 mg/kg in carriers and 0.5 or 1.0 mg/kg in noncarriers, every 13 weeks for 78 weeks. Volumetric outcomes included annualized brain, ventricular, and mean hippocampal boundary shift integrals (BBSI; VBSI; HBSI) up to Week 71. Treatment differences were estimated using mixed models for repeated measures. Results:For BBSI and HBSI, there were no significant treatment-related differences within either study, but, compared to pooled carriers and noncarriers receiving placebo, noncarriers receiving1.0 mg/kg bapineuzumab had greater increases in these measures. Bapineuzumab-treated patients showed significantly greater VBSI rates compared with placebo for 0.5 mg/kg in carriers and 1.0 mg/kg (but not 0.5 mg/kg) in noncarriers. Conclusions:Bapineuzumab produced an increase in ventricular volume compared with placebo. Etiology for this increase is unclear but may be related to amyloid-β clearance or its consequences.

Keywords: Alzheimer’s disease, bapineuzumab, brain boundary shift integral, brain volume, hippocampal boundary shift integral, magnetic resonance imaging, randomized controlled trial, ventricular boundary shift integral, ventricular volume

DOI: 10.3233/JAD-150448

Journal: Journal of Alzheimer's Disease, vol. 49, no. 4, pp. 1123-1134, 2016