Monoclonal Antibodies confer minor Benefits among Alzheimer Dementia cases

A recent study published in The Annals of Family Medicine concluded that monoclonal antibodies targeting amyloid do not offer clinically meaningful benefits, and they are expensive and carry risks.

The team conducted a meta-analysis to evaluate the clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in Alzheimer's dementia patients. They searched PubMed, Cochrane CENTRAL, five trial registries, and reference lists of identified studies. They included RCTs comparing a monoclonal antibody with a placebo at a dose consistent with phase 3 trials or FDA approval. Studies had to report at least 1 clinically relevant benefit or harm. Cognitive and functional scales were compared and assessed for each difference to determine if they met the minimal clinically important difference (MCID).

Key points of the study are:

• Nineteen publications were identified, including 23,202 participants evaluating eight anti-amyloid antibodies.
• Minor improvements over placebo were seen in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score. The standardized mean difference was −0.07.
• The values for the Mini-Mental State Examination score were 0.32 points.
• The mean and standardized mean difference for the Clinical Dementia Rating-Sum of Boxes scale and combined functional scores were 0.18 and 0.09, respectively.
• None of the changes, including those for aducanumab, lecanemab, , and donanemab, exceeded the MCID.
• Harms included significantly increased namyloid-related imaging abnormalities (ARIA)-oedema risk (relative risk of 10.29, and NNH 9 ).
• The RR for ARIA-hemorrhage and symptomatic ARIA-edema were 1.74 and 24.3 respectively. The NNH were 13 and 86, respectively.

Alzheimer's disease poses a significant challenge for patients, their families, and the healthcare system, as it causes significant suffering, burdens, and high costs.

Monoclonal antibodies targeting amyloid provide small benefits in cognitive and functional scales for Alzheimer's dementia patients, but the improvements are far below the MCID for each outcome and come with clinically meaningful harms.

Reference:

Ebell, M. H. et al. Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and Meta-Analysis. The Annals of Family Medicine, 22(1), 50–62. https://doi.org/10.1370/afm.3050