#369 Remind me, do medications that target brain amyloid improve my dementia?
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- Aducanumab: 2 RCTs, 3285 patients, terminated for futility.1-3 Re-analysis found benefit in one dosage arm (10mg/kg) of one RCT. Outcomes at 18 months:
- Clinical Dementia Rating-Sum of Boxes (CDR-SB) [scale 0-18, minimum clinically important difference=1-2]: 0.4 better with aducanumab, not clinically meaningful.4
- MMSE: 0.6 better,1 not clinically meaningful.4
- Harms:2,5 Amyloid related imaging abnormalities (ARIA).
- ARIA-E (brain edema): 35% versus 2.7% placebo; number needed to harm (NNH)=3.
- ARIA-H (brain microhemorrhage): 21% versus 6.5% placebo; NNH=7.
- Lecanemab: 1795 patients.6 At 18 months:
- CDR-SB: 0.5 better with treatment.
- ARIA-H: 17% versus 9% placebo (NNH=13).
- ARIA-E: 13% versus 1.7% placebo (NNH=10).
- Infusion reactions: 26% versus 7.4% placebo (NNH=6).
- Stopped due to adverse events: 6.9% versus 2.9% (NNH=25).
- Donanemab: 1736 patients with early Alzheimer’s (MMSE~22).7 At ~20 months:
- CDR-SB: 0.7 better with treatment.
- ARIA-E or H: 37% versus 15% placebo (NNH=5).
- Stopped due to adverse events: 13.1% versus 4.3% (NNH=12).
- Mortality: 1.9% versus 1.1% placebo: No statistics performed.
- Limitations: Multiple outcomes reported, often without statistical correction; other outcomes (example MMSE) missing; potential unblinding due to adverse events. Clinical importance of ARIAs is unclear. Work-up required additional investigation/ hospitalization.3
- Other RCTs demonstrate no meaningful benefit for crenezumab,8 solanezumab,9,10 and gantenerumab.11
- Systematic review (14 RCTs): Amyloid-targeting medications do not improve dementia.12
- No amyloid-targeting dementia medication currently approved in Canada.13
- Annual cost (not including infusion and other pre/post treatments): $25,000-55,000 (US).2,13
- Donepezil similar efficacy (1.1 MMSE improvement versus 0.6 Aducanumab), without serious harms.14
Good to know
strongly agree
Not approved in Canada