Aducanumab: patients whose amyloid cleared declined less, in an exploratory analysis

Design

Exploratory post hoc analysis of phase 3 trials and their extension and re-dosing studies

Population

Aducanumab-treated participants with early Alzheimer's disease in the amyloid PET substudy

Primary outcome

Clinical decline stratified by amyloid clearance at week 78

Effect

Less decline with clearance at weeks 78 and 134; about two-thirds declined <1 CDR-SB point per year

Investigators pooled aducanumab-treated participants from the ENGAGE and EMERGE phase 3 trials who had amyloid PET and continued into the long-term extension, or returned for the EMBARK re-dosing study up to two and a half years after the trials stopped. They compared those who had reached treatment-related amyloid clearance by week 78 with those who had not.

Those with clearance declined less at week 78, at week 134 and at re-entry after the treatment gap. After clearance, decline varied widely, but about two-thirds lost less than one point a year on the Clinical Dementia Rating Sum of Boxes.

The finding fits the idea that removing amyloid is what matters, and that the benefit may persist after dosing stops. But it compares people by a result achieved on treatment rather than by randomised group. Those who cleared amyloid may differ — in baseline load, dose tolerance or disease stage — in ways that also predict slower decline. Aducanumab has been withdrawn from the market; the relevance is to how clearance-based dosing with current antibodies is judged.

• Amyloid clearance on PET was associated with slower decline, supporting clearance as a treatment target.
• Decline after clearance was variable; clearance does not guarantee stability.
• These data inform debate on stopping anti-amyloid antibodies once amyloid has cleared.
• Aducanumab is no longer marketed; apply the principle to current agents with caution.

Why it matters

It bears on whether anti-amyloid antibodies can be stopped once PET shows clearance.

Don't overread it

Grouping by an on-treatment result, not randomisation, cannot show that clearance caused the slower decline.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.