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

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Abstract

Background

Studies targeting amyloid-ß in patients with Alzheimer’s disease (AD) have conflicting results and early initiation of therapy may yield better outcomes.

Methods

We 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.

Results

Nineteen 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).

Conclusion

Anti-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.

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Data availability

Data availability is not applicable to this article as no new data were created or analyzed in this study.

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Authors and Affiliations

  1. Universidade Federal do Rio Grande do Norte, Av. Nilo Peçanha, 620 - Petrópolis, Natal, RN, 59012-300, Brazil

    Julyana M. Dantas

  2. Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Antonio Mutarelli

  3. Universidade Eduardo Mondlane, Maputo, Mozambique

    Denilsa D. P. Navalha

  4. Universidade do Extremo Sul Catarinense, Criciúma, Brazil

    Caroline S. Dagostin

  5. Centro Universitário de Maceió, Maceió, Brazil

    Pedro H. C. L. Romeiro

  6. Universidade Federal de Campina Grande, Campina Grande, Brazil

    Nicole Felix & Larissa Teixeira

  7. Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil

    Alleh Nogueira

  8. Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Sávio Batista

  9. Behavioral and Cognitive Neurology Unit, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Paulo Caramelli

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Contributions

JMD (conception and design, study selection, analysis of data, risk of bias assessment, writing draft, review, and editing); PHCLR (acquisition of data, writing draft, and figures); CSD (acquisition of data, analysis of data, risk of bias assessment, writing draft, review, and editing); NF (analysis of data, writing draft, review, and editing); DDPN (study selection, acquisition of data, writing draft); AM (acquisition of data, risk of bias assessment, writing draft); SB (acquisition of data, writing draft, review, and editing); LT (conception and design, figures, writing draft); AN (analysis of data, review ,and editing); PC (conception and design, study selection, review, and editing).

Corresponding author

Correspondence to Julyana M. Dantas.

Ethics declarations

Ethics approval

This is a systematic review and meta-analysis. No ethical approval was required as no new patient data was collected.

Conflict of interest

Dr. Caramelli declares participation in an advisory board for Roche, the sponsor for CREAD, CREAD2, and SCarlet RoAD. Dr. Caramelli has also developed material for continuous medical education and participation as a speaker in symposia sponsored by Aché, Knight Therapeutics, Roche, and Torrent laboratories. The remainder of the authors have no competing interests to declare. The authors did not receive support from any organization for the submitted work.

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Dantas, J.M., Mutarelli, A., Navalha, D.D.P. et al. Efficacy of anti-amyloid-ß monoclonal antibody therapy in early Alzheimer’s disease: a systematic review and meta-analysis. Neurol Sci 45, 2461–2469 (2024). https://doi.org/10.1007/s10072-023-07194-w

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