Setting Realistic Expectations for Antiamyloid Therapeutics

EP: 1.Donanemab Dosing and ARIA Risk in TRAILBLAZER-ALZ 6

EP: 2.Maintaining Efficacy in Safer Donanemab Dosing Regimen

EP: 3.Importance of Patient Selection and Future Therapies in Alzheimer Treatment

EP: 4.Eligibility and Safety Considerations for Antiamyloid Alzheimer Therapies

EP: 5.Monitoring and Managing ARIA in Antiamyloid Treatments

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EP: 6.Setting Realistic Expectations for Antiamyloid Therapeutics

At the 2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, Alzheimer disease (AD) expert Sharon Cohen, MD, FRCPC, spoke with NeurologyLive^® to discuss the use of emerging AD therapies, specifically focusing on approved antiamyloid antibodies lecanemab (Leqembi; Eisai) and donanemab (Kisulna; Eli Lilly). In this part of the video series, Cohen highlighted key differences between these AD treatments, such as eligibility requirements and safety protocols. She also highlighted amyloid related imaging abnormalities (ARIA) risks and the importance of aligning patient expectations with treatment goals.

In the sixth episode of this AAIC Special Report, Cohen discussed the importance of setting realistic expectations for antibody treatments in mild AD. She emphasized that these therapies are intended to slow disease progression and help patients maintain their current level of function, rather than cure or substantially improve the disease. Cohen also highlighted key considerations, including the risks of symptomatic ARIA, the need for MRI monitoring, and access to infusion centers, noting that real-world data show most patients and clinicians find the treatment both beneficial and manageable.

Transcript below edited for clarity.

Sharon Cohen, MD, FRCPC: Treatment expectations need to be clarified, and we are prescribing these antibodies for the opportunity to keep mild patients mild, to keep them functioning at the level they're accustomed to for as long as possible. We're not expecting to cure the disease, and we're not telling people that the treatment will improve them, although what we see in some long-term data is that people who start out with a low burden of amyloid or tau tend to stay stable longer, and some of them even improve. So it is possible people can improve, but the overall expectation is that we will slow down your disease, "We will keep you mild longer. Is that something you're interested in?"

In my experience, most patients say, "Yes, I want that." But if somebody is hell-bent on, "No, I only want something if it's going to make me better," then maybe this isn't the treatment for them. Then you need to have the conversation about, is staying mild longer a benefit that outweighs the small risk of symptomatic ARIA, and if so, are you willing to undergo the MRI monitoring schedule? How would that work? Do you, in your own geography or with social support, have access to MRIs? I guess I should back up and say access to infusion centers. Although in the future, we're looking forward to subcutaneous dosing—at least for lecanemab—right now, at least for the first 18 months with lecanemab, we need access to an intravenous infusion center.

These are some of the considerations that are discussed. But real-world evidence shows us that we have many thousands of patients now who have been treated, and what the real-world data shows us is the vast majority are compliant and satisfied, and their clinicians are satisfied that the treatment is beneficial and worthwhile. So that's good news.