Longitudinal clinical outcomes after amyloid clearance in aducanumab phase 3 studies.
Menglan Pang, Holly M Brothers, John O'Gorman et al.
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In 30 seconds
This exploratory analysis pooled participants from the randomized phase 3 ENGAGE and EMERGE aducanumab trials who entered a long-term extension or later redosing study. It examined whether treatment-related amyloid clearance (TRAC) by week 78 was associated with clinical outcomes. Participants who achieved TRAC had less clinical decline at week 78, week 134, and the later study baseline than those who did not. After clearance, outcomes varied; approximately two thirds of TRAC participants had annualized decline of < 1 point on the Clinical Dementia Rating Sum of Boxes.
Key findings
- TRAC participants had less clinical decline than non-TRAC participants at week 78, week 134, and EMBARK baseline.
- Approximately two thirds of TRAC participants had annualized decline of < 1 point on the Clinical Dementia Rating Sum of Boxes after TRAC.
- Clinical decline after TRAC was heterogeneous.
Why it matters
The findings suggest that amyloid clearance during aducanumab treatment was associated with better clinical outcomes across subsequent assessments, while also showing that clearance did not correspond to a uniform course. This distinction is relevant when interpreting amyloid biomarker response alongside clinical change and underscores the variability of outcomes among participants who achieved clearance.
What to keep in mind
These were exploratory analyses stratified by TRAC status, not a randomized comparison of clearance versus no clearance; the abstract does not establish that clearance caused the differences in clinical outcomes.