Passive antiamyloid immunotherapy for Alzheimer's disease

Author(s)

Loureiro, Julia C. ^[1] ; Pais, Marcos V. ^[1] ; Stella, Florindo ^{[2, 1]} ; Radanovic, Marcia ^[1] ; Teixeira, Antonio Lucio ^{[3, 4]} ; Forlenza, Orestes V. ^[1] ; de Souza, Leonardo Cruz ^{[5, 6]}

Affiliation

^[1] Univ Sao Paulo, Hosp Clin HCFMUSP, Dept & Inst Psiquiatria, Lab Neurociencias LIM 27, Fac Med, Sao Paulo - Brazil

^[2] Univ Estadual Paulista UNESP, Inst Biociencias, Rio Claro - Brazil

^[3] Univ Texas Hlth Sci Ctr Houston UTHealth, McGovern Med Sch, Dept Psychiat & Behav Sci, Houston, TX - USA

^[4] Univ Fed Minas Gerais, Santa Casa BH Ensino & Pesquisa, Belo Horizonte, MG - Brazil

^[5] Univ Fed Minas Gerais, Programa Posgrad Neurociencias, Belo Horizonte, MG - Brazil

^[6] Univ Fed Minas Gerais, Dept Clin Med, Fac Med, Belo Horizonte, MG - Brazil

• Document type: Review article
• Source: CURRENT OPINION IN PSYCHIATRY; v. 33, n. 3, p. 284-291, MAY 2020.
• Web of Science Citations: 1

Abstract

Purpose of review Antiamyloid therapy of Alzheimer's disease tackles the overproduction and clearance of the amyloid-beta peptide (A beta). Immunotherapeutic compounds were tested in large-scale trials. We revisit the recent literature focusing on randomized-controlled trials (RCT) using monoclonal anti-A beta antibodies. Recent findings Forty-three articles on anti-A beta 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. Passive 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. (AU)

• FAPESP's process: 09/52825-8 - Neurobiology of Alzheimer's disease: risk markers, prognosis and therapeutic response
• Grantee: Wagner Farid Gattaz
• Support Opportunities: Research Projects - Thematic Grants