To understand the added clinical benefits of continuing an anti-amyloid therapy (AAT) beyond plaque clearance in early Alzheimer’s disease (AD) compared to stopping treatment, so HCPs can make better informed decisions about AD treatment approaches.
Two amyloid-b targeting mAbs, lecanemab and donanemab, have received traditional FDA approval and been shown to slow disease progression in early AD. In clinical trials the active and placebo groups continue to diverge after treatment ends, which can be misinterpreted as a continued accumulation of benefit when it actually may be due to the previously treated group maintaining a milder state (and thus having a slower rate of progression).
Participants in TRAILBLAZER-ALZ 2 who cleared plaques by 12 months with donanemab and switched to placebo were used to evaluate the treatment benefit of maintaining a milder disease state after stopping therapy. Comparing that group to the full study population may be inappropriate, so we compared them to a stimulated placebo group with matched characteristics and disease severity at 12 months to calculate % slowing from 12-18 months. To study the accumulating continuous-treatment benefit with ongoing lecanemab therapy, we mapped the progression of the full CLARITY-AD placebo group to those taking lecanemab between months 12-18 and calculated the percent slowing.
When early completers with donanemab were compared to an appropriate placebo group, the percent slowing was approximately 17% for the 6 months after stopping therapy at plaque clearance (months 12-18). When lecanemab treated participants continued therapy during the last 6 months of the double-blind phase, the percent slowing was approximately 29%.
Our findings suggest that although discontinuing donanemab at plaque clearance would show a persistent treatment benefit, continuing treatment with lecanemab beyond 12 months results in additional accumulation of benefit. This finding suggests that continuing treatment with lecanemab is superior to stopping treatment with donanemab.