Amyloid-beta-targeting monoclonal antibodies in early Alzheimer's disease: a cochrane review summary and appraisal for the neurological community.

Abstract

Background: Seven amyloid-beta-targeting monoclonal antibodies have been trialled in early Alzheimer's disease. They differ in epitope and in how much plaque they clear; only two have traditional approval. A 2026 Cochrane Review pooled all seven as one class. We ask what that average tells us about any one drug.

Methods: We summarise the review in mild cognitive impairment or mild dementia due to Alzheimer's disease and report its estimates and certainty ratings unchanged. Our appraisal sits in a separate section and draws on the pivotal trials and regulatory assessments.

Results: Seventeen trials (20,342 participants) were included. At 18 months the pooled standardised mean difference was -0.11 (95 % confidence interval -0.16 to -0.06) for cognition and -0.12 (-0.24 to 0.00) for dementia severity; three functional scales favoured treatment (0.09 to 0.23). Amyloid-related imaging abnormalities with oedema affected 119 versus 12 per 1,000 (risk ratio 10.02, 7.49 to 13.41). Four of the seven antibodies cleared no plaque or cleared it incompletely, so the pooled result cannot test whether clearance produces benefit. In the two approved agents dementia severity differed by 0.45 and 0.67 points, larger than the class average but below thresholds of clinical importance.

Conclusions: The class average is not an estimate for any single agent. These antibodies clear amyloid and produce small differences on trial scales at 18 months, against a tenfold rise in amyloid-related oedema. Counselling should rest on agent-specific figures and a biomarker-confirmed diagnosis, and should weigh APOE ε4 genotype and antithrombotic use before the first infusion.