The recent introduction of anti-amyloid monoclonal antibody treatments, such as lecanemab (Leqembi) and aducanumab (Aduhelm), has raised hopes for the treatment of early Alzheimer’s disease. However, a cross-sectional study conducted by the Mayo Clinic Study of Aging has revealed that the eligibility criteria for these treatments exclude the majority of individuals with early Alzheimer’s disease. This article aims to critically analyze the study findings and their implications for the availability and effectiveness of these treatments.
The study found that out of 237 participants with mild cognitive impairment or mild dementia and increased brain amyloid on PET, only 8% would qualify for a lecanemab trial based on the strict inclusion and exclusion criteria. The researchers discovered that modifying the exclusion criteria by not applying additional cognitive criteria increased the eligibility to 17.4% of participants with mild cognitive impairment. These findings indicate that the eligibility criteria for lecanemab significantly restrict the number of individuals who can receive this treatment.
Restricted Accessibility of Aducanumab
Similarly, the study revealed that the inclusion and exclusion criteria for aducanumab reduced the number of eligible candidates to only 5.1% of the cohort. The limited accessibility of aducanumab raises concerns about the availability of this treatment for individuals with early Alzheimer’s disease. The researchers argue that the restrictive criteria are necessary due to the resource-intensive nature of monoclonal antibody therapies and the potential for adverse events. However, these criteria significantly limit the number of individuals who can benefit from this treatment.
The study authors highlight that the low eligibility rate for both lecanemab and aducanumab is primarily due to chronic health conditions and brain scan abnormalities commonly found in older adults. In general, clinical trial participants are healthier than the general population, which raises concerns about the generalizability of trial findings to real-world populations. It is crucial to conduct additional research on larger, more diverse populations and individuals with poorer health to examine the safety and efficacy of these monoclonal antibody treatments.
While anti-amyloid drugs like lecanemab and aducanumab show clinical benefits, they also pose safety risks. These drugs can cause amyloid-related imaging abnormalities (ARIA), including effusions and edema (ARIA-E) or bleeding (ARIA-H). The editorialists accompanying the study highlight the potential seriousness and even fatality of ARIA. Individuals carrying the APOE4 allele and those with underlying cerebral amyloid angiopathy are at increased risk for cerebral edema and microhemorrhage. It is essential to weigh the potential benefits against the risks when considering these treatments for individuals at higher risk.
Prescribing Information and Recommendations
The prescribing information for lecanemab was updated in July 2023, following its full approval. It now includes a black box warning about ARIA and recommends caution when treating patients on anticoagulants. Anticoagulation increases the risk of hemorrhage, leading to more restrictive recommendations stating that patients requiring anticoagulants should not receive lecanemab until more data are available. These precautions reflect the need for careful consideration of individual risk factors when prescribing anti-amyloid monoclonal antibodies.
The Need for Further Research
The study findings emphasize the necessity for additional research to collect real-world data on the eligibility, safety, and efficacy of anti-amyloid monoclonal antibodies. The researchers suggest that registries like ALZ-NET should be utilized to gather comprehensive data on a more diverse population, including underrepresented racial and ethnic groups. This research is essential for determining the broader applicability of these treatments and ensuring equitable access for all individuals with Alzheimer’s disease.
The Mayo Clinic Study of Aging highlights the limited eligibility of anti-amyloid monoclonal antibody treatments for individuals with early Alzheimer’s disease. The strict inclusion and exclusion criteria significantly restrict the number of eligible candidates, primarily due to chronic health conditions and brain abnormalities common in older adults. Safety concerns, such as the risk of ARIA, further complicate the administration of these drugs. It is crucial to conduct further research on larger and more diverse populations to establish the safety and efficacy of these treatments in real-world settings. Only then can these treatments become more widely available and accessible to all individuals with Alzheimer’s disease.