Key Information
Abstract
Years of experience watching our patients progressively decline and die from complications of Alzheimer's disease (AD) has strongly motivated us to provide newly approved anti‐amyloid treatments to appropriate patients. Following detailed and personalized discussions of the potential risks and benefits of these treatments with patients and their families, almost 300 patients at our clinic have chosen to receive lecanemab infusions. We have found the frequency and severity of complications, including amyloid‐related imaging abnormalities (ARIA), to be manageable and as expected based on clinical trials. While the longer‐term benefits of these treatments are not yet clear, our patients and their families are accepting of even a modest slowing of disease progression. We have experienced the complexities, burdens, costs, and major logistical challenges associated with the treatment of AD with anti‐amyloid treatments. However, we also understand that for some of our current patients with early symptomatic AD, anti‐amyloid treatments are their best option for fighting this devastating disease, and we find it worthwhile to provide these treatments to our patients.
Highlights
Many of our former patients have died from complications of AD.
Our clinic now has nearly 300 patients receiving anti‐amyloid treatments.
We have found the complications of anti‐amyloid treatments to be manageable.
Despite the challenges, we find anti‐amyloid treatments worthwhile.
1.
Each of us has diagnosed and treated patients with Alzheimer's disease (AD) for many years. We do our best to provide accurate diagnoses, address exacerbating issues, eliminate sedating medications, and treat sleep and mood disorders. We recommend a healthy diet, exercise, cognitive stimulation, and acetylcholinesterase inhibitors and other medications as appropriate. However, persons with symptomatic AD inevitably decline, and, despite our best efforts, we have watched many of our patients progressively worsen and eventually die from complications of AD.
Because we understand the terrible toll of AD, we were encouraged when lecanemab (Leqembi), an anti‐amyloid monoclonal antibody, received traditional approval from the US Food and Drug Administration (FDA) for the treatment of early symptomatic AD in July of 2023. 1 external link, opens in a new tabThe subsequent coverage decision by the Center for Medicare and Medicaid Services made this therapy potentially available to millions of Americans. Our memory clinic at Washington University has been a site for multiple clinical trials of anti‐amyloid treatments, which provided experience that we have translated into clinical care. Nearly 300 of our patients are currently receiving lecanemab infusions.
The major side effects of anti‐amyloid antibodies are amyloid‐related imaging abnormalities (ARIA) with hemorrhage or hemosiderin deposits (ARIA‐H) or edema (ARIA‐E). 2 external link, opens in a new tabIn the CLARITY‐AD trial, 1 external link, opens in a new tabARIA‐H was found in 17.3% of lecanemab‐treated and 9.0% of placebo‐treated participants, while ARIA‐E was observed in 12.6% of lecanemab‐treated and 1.7% of placebo‐treated participants. 1 external link, opens in a new tabImportantly, ARIA is a radiographic finding and is asymptomatic in most cases: in the CLARITY‐AD trial, only 31 of 898 treated participants (3.5%) had any symptoms from ARIA. 1 external link, opens in a new tabRates of ARIA in our clinic have been similar to those reported by CLARITY‐AD with most ARIA being asymptomatic and radiographically mild. 3 external link, opens in a new tabEven in patients with symptoms, ARIA has typically resolved within 4 to 8 weeks of stopping treatment, and steps have been taken to reduce the risk of severe complications. 4 external link, opens in a new tabOverall, the frequency and severity of side effects from lecanemab have been as expected and have been manageable.
Given our many years of caring for patients with AD, the published data, and our clinical experience, we have been disheartened by reports of anti‐amyloid treatments that do not put risks into context. An article in Science featured brain MRI images of severe ARIA and described complications of anti‐amyloid treatments as “brain swelling and bleeding, which in clinical trials affected up to about one‐third of patients and ranged from asymptomatic to fatal.” 5 external link, opens in a new tabDescriptions that lump together completely different outcomes may lead to a misperception that severe complications are common rather than only occurring in ∼1% to 2% of patients receiving anti‐amyloid treatments. Describing ARIA‐H as “brain bleeding” is particularly problematic because this term evokes a macrohemorrhage rather than typical ARIA‐H findings, such as one or two ∼1 mm microhemorrhages. Some articles describe smaller brain volumes in patients treated with anti‐amyloid antibodies as a mysterious and malignant effect 6 external link, opens in a new tabwithout mentioning reassuring possible explanations such as decreased inflammation. 7 external link, opens in a new tabOther articles state that death is a significant risk and recount a handful of cases reported over several years. 8 external link, opens in a new tab, 9 external link, opens in a new tab, 10 external link, opens in a new tabAgain, we think it is essential to provide this information in context – serious complications related to ARIA can and do occur, but they are rare.