Gantenerumab is a fully human monoclonal antibody currently under evaluation at titrated subcutaneous doses of ≤1200mg monthly. Gantenerumab has demonstrated high levels of amyloid reduction on positron emission tomography (PET) in patients with AD.

To characterize amyloid reductions among patients with and without amyloid-related imaging abnormalities–edema (ARIA-E) during the open-label extension (OLE) of the SCarlet RoAD (SR; NCT01224106) and Marguerite RoAD (MR; NCT02051608) studies of gantenerumab in patients with Alzheimer’s disease (AD).

Amyloid PET reductions were quantified using a prespecified method described previously and a centiloid transformation. The analysis included all patients with Week 52 and 104 PET scans from MR/SR OLE studies. Baseline amyloid load, global and regional amyloid reduction and cumulative gantenerumab dose were included in the analysis. Voxel-wise amyloid PET reductions were also examined.

Global baseline amyloid load was not significantly different between ARIA-E and non–ARIA-E groups. A total of 373 MR/SR OLE patients had an overall ARIA-E rate of 30.6%. Among 67 PET OLE patients scanned at Week 52, 28 (41.8%) experienced ARIA-E; of these, 7 (25%) were symptomatic. Large amyloid reductions (–38 centiloid at Week 52 and –59 centiloid at Week 104 overall), often below the amyloid positivity threshold, were seen in both patients with and without ARIA-E. There were no significant differences between the ARIA-E and non–ARIA-E groups at either Week 52 or 104. However, regional focal reductions were frequently seen in voxel-wise analyses of ARIA-E patients.

Large amyloid reductions are consistently seen in ARIA-E and non–ARIA-E groups treated with high-dose gantenerumab.