title: Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Alzheimer's disease (AD) is a globally prevalent neurodegenerative condition, clinically characterized by progressive memory loss and gradual impairment of cognitive functions. Bapineuzumab is a fully humanized monoclonal antibody that binds to neurotoxic amyloid proteins in the brain, enhancing their clearance. We performed this systematic review and meta-analysis to evaluate the safety and efficacy of bapineuzumab in patients with mild to moderate Alzheimer's disease.
  
  
  METHODS
  We performed a web-based literature search of PubMed, Ovid, EBSCO, Scopus, Embase, Cochrane CENTRAL, and web of science using the relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (CI), using Review Manager software (﻿version 5.3 for windows). Heterogeneity was measured by Chi-square and I-square tests.
  
  
  RESULTS
  The pooled effect estimate from six randomized clinical trials (n = 2380) showed that bapineuzumab significantly reduced the cerebrospinal fluid concentration of phosphorylated tau proteins (Standardized MD = -5.53, 95% CI [-8.29, -2.76]). However, the bapineuzumab group was not superior to the placebo group in terms of change from baseline in Alzheimer's disease assessment scale (ADAS)-Cog11 (MD = 0.14, 95% CI [-0.72, 0.99]), disability assessment for dementia (DAD) scale (MD = 1.35, 95% CI [-1.74, 4.43]), and mini-mental state examination (MMSE) scores (MD = 0.08, 95% CI [-0.31, 0.47]). Regarding safety, bapineuzumab increased the risk of serious treatment-emergent adverse events (RR = 1.18, 95% CI [1.02, 1.37]) and cerebral vasogenic edema (RR = 40.88, 95% CI [11.94, 135.95]). All bapineuzumab doses (0.15, 0.5, 1, and 2 mg/kg) were similar to placebo in terms of change from baseline in ADAS-cog11, DAD, and MMSE scores, except for the 0.15 mg/kg dose, which caused a significant worsening on the ADAS-cog11 scale (MD = 5.6, 95% CI [0.22, 10.98]).
  
  
  CONCLUSIONS
  Considering the lack of clinical efficacy, combined with the significant association with serious adverse events, bapineuzumab should not be used to treat patients with mild to moderate AD. Future studies should investigate the effect of combining bapineuzumab with other therapeutic strategies and reevaluate the efficacy of targeting amyloid β proteins in AD therapy.
authors.affiliation: Faculty of Medicine, Ain Shams University, Cairo, Egypt.|NovaMed Medical Research Association, Cairo, Egypt.
authors.forename: Abdelrahman Ibrahim
authors.initials: AI
authors.lastname: Abushouk
authors.affiliation: NovaMed Medical Research Association, Cairo, Egypt.|Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elmaraezy
authors.affiliation: Faculty of Medicine, Tanta University, Tanta, Egypt.
authors.forename: Amro
authors.initials: A
authors.lastname: Aglan
authors.affiliation: Faculty of Medicine, Benha University, Qaluobia, Egypt.
authors.forename: Reham
authors.initials: R
authors.lastname: Salama
authors.affiliation: Faculty of Medicine, Zagazig University, Elsharkia, Egypt.
authors.forename: Samar
authors.initials: S
authors.lastname: Fouda
authors.affiliation: Faculty of Medicine, Zagazig University, Elsharkia, Egypt.
authors.forename: Rana
authors.initials: R
authors.lastname: Fouda
authors.affiliation: Faculty of Medicine, Damascus University, Damascus, Syria. Ammar.m.alsafadi@gmail.com.
authors.forename: Ammar M
authors.initials: AM
authors.lastname: AlSafadi
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C545458:bapineuzumab
keywords: Alzheimer’s disease; Bapineuzumab; Dementia; Passive immunotherapy