Fewer than 10% of patients with mild cognitive impairment (MCI) or early Alzheimer disease (AD) meet all criteria to participate in pivotal clinical trials for the 2 newest approved anti-amyloid drug treatments, according to the findings of a cross-sectional study published in the journal Neurology.
This population-based study echoes previous research from specialized clinics, indicating that many patients receiving care for early AD would not match the clinical trial eligibility criteria for aducanumab. No comparable reports were available for lecanemab, the other anti-amyloid drug to receive accelerated US Food and Drug Administration (FDA) approval.
To test this assertion in community-dwelling adults, researchers analyzed data from the Mayo Clinic Study of Aging (MCSA), an ongoing population-based cohort study. They extracted case data from 2009 onwards; patients in the dataset were age 50 and older, with magnetic resonance imaging (MRI) scan and Pittsburgh Compound B positron emission tomography (PET) data available, as well as data from cognitive testing and apolipoprotein E (APOE) ε4 screening.
This yielded a population of 237 patients who had an amyloid-positive PET scan, a diagnosis of either MCI or mild dementia with suspicion of AD, and a reported Clinical Dementia Rating score. The mean age of these patients was 80.9; 55% were men; and most were White. The researchers then applied participant eligibility criteria from the respective pivotal trials for aducanumab and lecanemab.
For lecanemab, applying inclusion criteria reduced the eligible study population from 237 to 112 (47%), largely due to body mass index (BMI) and cognitive test scores. Of those 112 patients, 19 also satisfied the exclusion criteria (8% of the initial 237). Both cardiopulmonary and other central nervous system (CNS) conditions would exclude roughly a third of patients; imaging findings would exclude nearly 38%, and malignancy 18%.
For aducanumab, 104 of the initial 237 participants (44%) fulfilled the inclusion criteria; other patients were most often screened out by age and cognitive test scores. Of these 104, 12 also met exclusion criteria (5% of the initial 237). Notable excluding conditions were similar to those under lecanemab criteria; but greater numbers were excluded from aducanumab by cardiovascular disease and cancers.
Patients meeting all eligibility criteria were mostly White; no eligible patient was Hispanic or Latinx. Both lecanemab- and aducanumab-eligible patients were disproportionately APOE ε4 positive, and less likely than excluded participants to have diabetes or heart disease.
MCSA patients without PET scan data available were universally excluded; compared with those with PET scans, MCSA patients tended to be older, had fewer years of education and lower Mini-Mental Status Examination (MMSE) scores, and were more likely to be cognitively impaired and to have at least 3 comorbidities.
Study limitations included a lack of racial and ethnic diversity, and relatively high level of education, in the MCSA patient population; and imperfect matches with pivotal trials’ inclusion and exclusion criteria, due to use of different disease classification systems.
These findings, they wrote, imply “a gap in treatment decision information (risk or benefit) for potential patients falling outside of the narrow clinical trial enrollment criteria.”
They concluded, “[T]he eligibility for anti-beta amyloid mAbs [anti-beta amyloid monoclonal antibody] treatment of patients with early AD, is limited due to exclusionary common conditions in the typical older adult populations.”
Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.
This article originally appeared on Neurology Advisor
Pittock RR, Aakre J, Castillo AM, et al. Eligibility for anti-amyloid treatment in a population-based study of cognitive aging. Neurology. Published online August 16, 2023. doi:10.1212/WNL.0000000000207770