The eligibility criteria for the new anti-amyloid monoclonal antibody treatments, lecanemab (Leqembi) and aducanumab (Aduhelm), have been found to significantly limit the number of people with early Alzheimer’s disease who can receive these treatments. This article critically examines the cross-sectional data from the Mayo Clinic Study of Aging, which reveals the low number of eligible candidates for these therapies.
According to the study’s findings, out of 237 individuals with mild cognitive impairment or mild dementia and increased brain amyloid on PET, only a small fraction met the eligibility criteria for the clinical trials of lecanemab and aducanumab. The researchers reported that modifications to the exclusion criteria slightly increased the number of eligible participants for lecanemab. However, even with these modifications, the percentage of eligible candidates remained low.
The study emphasizes that chronic health conditions and common brain scan abnormalities in older adults are major factors contributing to the limited eligibility of individuals with early Alzheimer’s disease. The analysis indicates that clinical trial participants are generally healthier than the general population, which further restricts the number of individuals who can receive these treatments.
Dr. Maria Vassilaki from the Mayo Clinic highlights the need for further research to examine the safety and efficacy of monoclonal antibodies targeting amyloid-beta plaques. It is crucial to study larger and more diverse populations, including individuals with less favorable health conditions, before making these therapies widely available to people with Alzheimer’s disease.
The study reveals that the trial inclusion and exclusion criteria for lecanemab and aducanumab differ, resulting in varying percentages of eligible candidates. A significantly higher number of individuals qualified for aducanumab compared to lecanemab. These differences may have implications for the selection of appropriate treatments based on individual patient factors.
In an accompanying editorial, Dr. Stephen Salloway and co-authors acknowledge the potential clinical benefits of anti-amyloid drugs while emphasizing the importance of assessing the risk-benefit ratio. They outline the risks associated with these therapies, particularly amyloid-related imaging abnormalities (ARIA). The editorial suggests that initial use should be restricted to patients most likely to benefit and least likely to experience harm, considering the resource-intensive nature of monoclonal antibody therapies.
Following the full approval of lecanemab, its prescribing information was updated with a black box warning about ARIA. This warning highlights the need for caution when treating patients on anticoagulants, as they are at higher risk of hemorrhage. The appropriate use recommendations now advise against administering lecanemab to patients requiring anticoagulants until more data become available.
The Mayo Clinic Study of Aging has several limitations that need to be considered. The inclusion and exclusion criteria could not be precisely defined as in the original trials, potentially affecting the results. Additionally, the sample included predominantly white participants, raising questions about the generalizability of the findings to racially and ethnically diverse populations. The researchers also emphasize the importance of collecting real-world data through registries to better understand the eligibility, safety, and efficacy of anti-amyloid monoclonal antibodies.
The limited eligibility of individuals with early Alzheimer’s disease for the new anti-amyloid monoclonal antibody treatments, lecanemab and aducanumab, poses significant challenges in providing these therapies to a wider population. The study highlights the influence of chronic health conditions, brain scan abnormalities, and the need for further research to address the safety and efficacy of these treatments. It also emphasizes the importance of carefully assessing the risk-benefit ratio and providing appropriate recommendations for their use. Moving forward, research efforts should focus on diversifying study populations and collecting real-world data to inform clinical decision-making.