Passive antiamyloid immunotherapy for Alzheimer's disease

Júlia C. Loureiro, Marcos V. Pais, Florindo Stella, Marcia Radanovic, Antônio Lúcio Teixeira, Orestes V. Forlenza, Leonardo Cruz De Souza

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations

Abstract

Purpose of reviewAntiamyloid therapy of Alzheimer's disease tackles the overproduction and clearance of the amyloid-beta peptide (Aβ). Immunotherapeutic compounds were tested in large-scale trials. We revisit the recent literature focusing on randomized-controlled trials (RCT) using monoclonal anti-Aβ antibodies.Recent findingsForty-three articles on anti-Aβ passive immunotherapy for Alzheimer's disease were published between January 2016 and October 2019 regarding 17 RCTs: 13 phase III trials using the monoclonal antibodies bapineuzumab, solanezumab, gantenerumab, crenezumab, and aducanumab; three phase II with crenezumab and aducanumab; and one phase I trial with BAN2401. Studies resulted largely negative considering the effect of the treatment on primary and secondary outcome variables. The incidence of the most important adverse effect, amyloid-related imaging abnormalities (ARIAs) ranged between 0.2 and 22%, in treatment groups. Primary endpoints were not met in eight trials, and five trials were discontinued prior to completion.SummaryPassive immunotherapy RCTs failed to show clinically relevant effects in patients with clinically manifest or prodromal dementia. The high incidence of ARIAs indicates that the risk of adverse events may outweigh the benefits of these interventions. Ongoing studies must determine the benefit of such interventions in preclinical Alzheimer's disease, addressing the effect of antiamyloid immunotherapy in samples of asymptomatic carriers of autosomal-dominant mutations related to early-onset Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)284-291
Number of pages8
JournalCurrent opinion in psychiatry
Volume33
Issue number3
DOIs
StatePublished - May 1 2020
Externally publishedYes

Keywords

  • Aducanumab
  • Alzheimer's disease
  • Crenezumab
  • Gantenerumab
  • Monoclonal antibody
  • Passive immunotherapy
  • Solanezumab

ASJC Scopus subject areas

  • Psychiatry and Mental health

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