By Lucy Piper, medwireNews reporter
medwireNews: Baseline amyloid level is a strong predictor of amyloid plaque clearance, proving more useful than age and tau level, analysis of data from the TRAILBLAZER-ALZ 2 trials suggest.
Sergey Shcherbinin (Eli Lilly and Company, Indianapolis, USA) presenting the findings at AD/PD 2024 in Lisbon, Portugal, commented that baseline tau and age can also be considered to better understand individual amyloid clearance.
Shcherbinin and colleagues conducted a post-hoc analysis of baseline factors among 639 participants from the TRAILBLAZER-ALZ 2 main study, who had early Alzheimer’s disease with both brain amyloid and tau pathology, and 822 from the TRAILBLAZER-ALZ 2 addendum study who had just brain amyloid pathology. The patients included in the analysis had received all of the scheduled monthly intravenous doses of donanemab (700 mg for the first three doses and 1400 mg thereafter) up to 24 and 52 weeks.
Using univariate logistic regression and machine learning models, the team identified 11 baseline characteristics from 41 and 31 in the two studies, respectively, that were associated with amyloid clearance (<24.1 centiloids) at 24 weeks of treatment with donanemab.
These factors included demographics, apolipoprotein E4 status, Mini-Mental State Examination (MMSE) score, imaging, and plasma measurements.
Five baseline factors common to both studies were significantly associated with amyloid clearance at 24 weeks, predicting the likelihood with an accuracy of 80% in the main study and 77% in the addendum study. Of these factors, low amyloid on positron emission tomography (PET) was ranked as the most important, followed by increased age, low bodyweight, absence of the apolipoprotein E4 allele, and low tau PET.
Multiple logistic regression analysis confirmed the significance of these five factors for predicting amyloid clearance and further factor evaluation suggested that baseline amyloid was the “strongest single predictor of amyloid plaque clearance at 24 weeks,” Shcherbinin reported, with an accuracy of 73%. The accuracy when all five predictive factors were used was 81%.
The findings were consistent across the two studies and for prediction of amyloid clearance at both 24 and 52 weeks, Shcherbinin noted, with baseline amyloid and age remaining the top two predictors across both the 24- and 52-week models.
Shcherbinin concluded: “These hypothesis-generating, post-hoc exploratory analyses require future work, including validation across amyloid-targeting therapies.”
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