Journal Article

Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer’s disease: a systematic review and meta-analysis

Romeiro, Pedro H. C. L, Caramelli, Paulo, Dantas, Julyana M, Dagostin, Caroline S, Felix, Nicole, Batista, Sávio, Teixeira, Larissa, Nogueira, Alleh, Mutarelli, Antonio, Navalha, Denilsa D. P

2024

Overview

BackgroundStudies targeting amyloid-ß in patients with Alzheimer’s disease (AD) have conflicting results and early initiation of therapy may yield better outcomes.MethodsWe systematically searched PubMed, Embase, Cochrane Library, and Clinicaltrials.gov for randomized trials comparing monoclonal antibodies (mAbs) with placebo in MCI or mild dementia due to AD.ResultsNineteen studies comprising 15,275 patients were included. In patients with early AD, mAbs reduced the rate of decline, in both the Clinical Dementia Rating Scale, the sum of boxes (CDR-SB; MD −0.30; 95% CI −0.42,−0.19; p < 0.01), and the Alzheimer’s Disease Assessment Scale, cognitive subscore (ADAS-cog; SMD −0.80; 95% CI −10.25,−0.35; p < 0.01). The results were similar between clinical stages for CDR-SB (MCI, MD −0.19; 95% CI −0.35,−0.03; p = 0.02; mild dementia, MD −0.45; 95% CI −0.65,−0.25; p < 0.01; subgroup differences, p = 0.13), as well as for ADAS-Cog (MCI, SMD −0.83; 95% CI −1.49,−0.17; p = 0.01; mild dementia, SMD −0.69; 95% CI −1.32 to −0.05; p = 0.03; subgroup differences, p = 0.47). The risk of amyloid-related imaging abnormalities (ARIA) was significantly higher in patients taking mAbs, including ARIA-edema (RR 7.7; 95% CI 4.60 to 13.00; p < 0.01), ARIA-hemorrhage (RR 1.8; 95% CI 1.22 to 2.59; p < 0.01), and symptomatic or serious ARIA (RR 14.1; 95% CI 7.30 to 27.14; p < 0.01).ConclusionAnti-amyloid-ß mAbs attenuate cognitive and functional decline compared with placebo in early AD; whether the magnitude of this effect is clinically important remains uncertain, especially relative to the safety profile of these medications. Starting immunotherapy in patients with MCI was not significantly different than starting in the mild dementia stage.PROSPERO registryCRD42023430698

• Publisher: Springer Nature B.V
• Subject: Alzheimer's disease / Clinical trials / Dementia / Dementia disorders / Edema / Hemorrhage / Immunotherapy / Meta-analysis / Monoclonal antibodies / Neurodegenerative diseases / Placebos / Systematic review