The online version of this article (doi:10.1186/s12883-017-0850-1) contains supplementary material, which is available to authorized users.
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.
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.
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]).
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.
Alzheimer's Association. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement. 2013;9:208–45. CrossRef
Salloway R, Gilman S, Fox NC, Blennow K, Raskind M, Sabbagh M, Honig LS, Doody R, van Dyck CH, Mulnard R, Barakos J, Gregg KM, Liu E, Lieberburg I, Schenk D, Black R, Grundman MSR. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology. 2009;73:2061–70. doi: 10.1212/WNL.0b013e3181c67808. PubMedPubMedCentralCrossRef
Rinne DJ, Rossor MN, Fox NC, Bullock R, Klunk WE, Mathis CA, Blennow K, Barakos J, Okello AA, Rodriguez Martinez de Liano S, Liu E, Koller M, Gregg KM, Schenk D, Black R, BJ GM. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol. 2010;9:363–72. doi: 10.1016/s1474-4422(10)70043-0. PubMedCrossRef
Arai H, Umemura K, Ichimiya Y, et al. Safety and pharmacokinetics of bapineuzumab in a single ascending-dose study in Japanese patients with mild to moderate Alzheimer’s disease. Geriatr Gerontol Int. 2016;7:S776–7.
Higgins JP, Green S. Cochrane Handbook for Systematic Reviews of interventions. The Cochrane Collaboration. 2008. doi: 10.1002/9780470712184.
Black RS, Sperling R, Kirby L, et al (2006) A single ascending dose study of bapineuzumab, a humanized monoclonal antibody to A-beta. AD, 9th international Geneva/Springfield symposium on advances in Alzheimer therapy.
Sperling R, Salloway S, Arrighi M, et al. Revised estimates of incidence and risk factors for amyloid related imaging abnormalities (ARIA) in the phase 2 studies of bapineuzumab for mild-to-moderate Alzheimer’s disease. Alzheimers Dement. 2011;7:e64. CrossRef
Novak G, Di J, Brashear RH, et al. Efficacy and safety of subcutaneous Bapineuzumab. Alzheimers Dement. 2014;10:P446–7.
Imbimbo S., Frisardi, V., Solfrizzi, V., Greco, A., Seripa, D., Pilotto, A., Panza, F., B P. O (2012) Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease. Expert Rev Clin Immunol 8:135–149. doi: 10.1586/eci.11.93.
- Bapineuzumab for mild to moderate Alzheimer’s disease: a meta-analysis of randomized controlled trials
Abdelrahman Ibrahim Abushouk
Ammar M. AlSafadi
- BioMed Central