Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Meta-Analysis

Safety Analysis of Bapineuzumab in the Treatment of Mild to Moderate Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Author(s): Yaqi Gao*, Jing Guo, Fang Zhang and Yanfang Li

Volume 27, Issue 1, 2024

Published on: 11 May, 2023

Page: [40 - 47] Pages: 8

DOI: 10.2174/1386207326666230419095813

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Alzheimer’s disease affects millions of people worldwide, and very few drugs are available for its treatment. Monoclonal antibodies have shown promising effects in the treatment of various types of diseases. Bapineuzumab is one of the humanized monoclonal antibodies, which have shown promising effects in AD patients. Bapineuzumab has shown efficacy in the treatment of mild to moderate Alzheimer’s disease. However, its safety is still unclear.

Objective: Thus, the main objective of the current study is to find out the exact safety profile of bapineuzumab in the treatment of mild to moderate Alzheimer’s disease.

Methods: We performed a web-based literature search of PubMed and clinical trial websites using the relevant keywords. Data were extracted from eligible records, and the risk ratio (RR) was calculated with a 95% confidence interval (CI). All the analyses were performed using Review Manager software (version 5.3 for windows). Heterogeneity was measured by Chi-square and I-square tests.

Results: Non-significant association of bapineuzumab with serious treatment-emergent adverse events [RR: 1.11 (0.92, 1.35)], headache [RR: 1.03 (0.81, 1.32)], delirium [RR: 2.21 (0.36, 13.53)], vomiting [RR: 0.92 (0.55, 1.55)], hypertension [RR: 0.49 (0.12, 2.12)], convulsions [RR:2.23 (0.42, 11.71)], falls [RR: 0.98 (0.80, 1.21)], fatal AEs [RR: 1.18 (0.59, 2.39)], and neoplasms [RR:1.81 (0.07, 49.52)] was reported; however, a significant association was found with vasogenic edema [RR: 22.58 (3.48, 146.44)].

Conclusion: Based on available evidence, bapineuzumab is found to be safe in the treatment of AD patients. However, vasogenic edema should be considered.

Keywords: Bapineuzumab, vasogenic edema, safety, Alzheimer’s disease, confidence interval (CI), risk ratio (RR).

« Previous Next »
Graphical Abstract

[1]
Goedert, M.; Spillantini, M.G. A century of Alzheimer’s disease. Science, 2006, 314(5800), 777-781.
[http://dx.doi.org/10.1126/science.1132814] [PMID: 17082447]
[2]
Karch, C.M.; Goate, A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry, 2015, 77(1), 43-51.
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455]
[3]
Xia, N.; Zhou, B.; Huang, N.; Jiang, M.; Zhang, J.; Liu, L. Visual and fluorescent assays for selective detection of beta-amyloid oligomers based on the inner filter effect of gold nanoparticles on the fluorescence of CdTe quantum dots. Biosens. Bioelectron., 2016, 85, 625-632.
[http://dx.doi.org/10.1016/j.bios.2016.05.066] [PMID: 27240009]
[4]
Nelson, P.T.; Alafuzoff, I.; Bigio, E.H. Correlation of Alzheimer disease neuropathologic changes with cognitive status: a review of the literature. J. Neuropathol. Exp. Neurol., 2012, 71, 362-381.
[http://dx.doi.org/10.1097/NEN.0b013e31825018f7]
[5]
Thies, W.; Bleiler, L. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement., 2013, 9(2), 208-245.
[http://dx.doi.org/10.1016/j.jalz.2013.02.003] [PMID: 23507120]
[6]
Melnikova, I. Therapies for Alzheimer’s disease. Nat. Rev. Drug Discov., 2007, 6(5), 341-342.
[http://dx.doi.org/10.1038/nrd2314] [PMID: 17539055]
[7]
Moreta, M.P.G.; Burgos-Alonso, N.; Torrecilla, M.; Marco-Contelles, J.; Bruzos-Cidón, C. Efficacy of acetylcholinesterase inhibitors on cognitive function in Alzheimer’s disease. Review of reviews. Biomedicines, 2021, 9(11), 1689.
[http://dx.doi.org/10.3390/biomedicines9111689] [PMID: 34829917]
[8]
Berger, M.; Shankar, V.; Vafai, A. Therapeutic applications of monoclonal antibodies. Am. J. Med. Sci., 2002, 324(1), 14-30.
[http://dx.doi.org/10.1097/00000441-200207000-00004] [PMID: 12120821]
[9]
Goure, W.F.; Krafft, G.A.; Jerecic, J.; Hefti, F. Targeting the proper amyloid-beta neuronal toxins: A path forward for Alzheimer’s disease immunotherapeutics. Alzheimers Res. Ther., 2014, 6(4), 42.
[http://dx.doi.org/10.1186/alzrt272] [PMID: 25045405]
[10]
Bard, F.; Cannon, C.; Barbour, R.; Burke, R.L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson-Wood, K.; Khan, K.; Kholodenko, D.; Lee, M.; Lieberburg, I.; Motter, R.; Nguyen, M.; Soriano, F.; Vasquez, N.; Weiss, K.; Welch, B.; Seubert, P.; Schenk, D.; Yednock, T. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med., 2000, 6(8), 916-919.
[http://dx.doi.org/10.1038/78682] [PMID: 10932230]
[11]
Bard, F.; Barbour, R.; Cannon, C.; Carretto, R.; Fox, M.; Games, D.; Guido, T.; Hoenow, K.; Hu, K.; Johnson-Wood, K.; Khan, K.; Kholodenko, D.; Lee, C.; Lee, M.; Motter, R.; Nguyen, M.; Reed, A.; Schenk, D.; Tang, P.; Vasquez, N.; Seubert, P.; Yednock, T. Epitope and isotype specificities of antibodies to β-amyloid peptide for protection against Alzheimer’s disease-like neuropathology. Proc. Natl. Acad. Sci., 2003, 100(4), 2023-2028.
[http://dx.doi.org/10.1073/pnas.0436286100] [PMID: 12566568]
[12]
Buttini, M.; Masliah, E.; Barbour, R.; Grajeda, H.; Motter, R.; Johnson-Wood, K.; Khan, K.; Seubert, P.; Freedman, S.; Schenk, D.; Games, D. β-amyloid immunotherapy prevents synaptic degeneration in a mouse model of Alzheimer’s disease. J. Neurosci., 2005, 25(40), 9096-9101.
[http://dx.doi.org/10.1523/JNEUROSCI.1697-05.2005] [PMID: 16207868]
[13]
Shankar, G.M.; Li, S.; Mehta, T.H.; Garcia-Munoz, A.; Shepardson, N.E.; Smith, I.; Brett, F.M.; Farrell, M.A.; Rowan, M.J.; Lemere, C.A.; Regan, C.M.; Walsh, D.M.; Sabatini, B.L.; Selkoe, D.J. Amyloid-β protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat. Med., 2008, 14(8), 837-842.
[http://dx.doi.org/10.1038/nm1782] [PMID: 18568035]
[14]
Zago, W.; Buttini, M.; Comery, T.A.; Nishioka, C.; Gardai, S.J.; Seubert, P.; Games, D.; Bard, F.; Schenk, D.; Kinney, G.G. Neutralization of soluble, synaptotoxic amyloid β species by antibodies is epitope specific. J. Neurosci., 2012, 32(8), 2696-2702.
[http://dx.doi.org/10.1523/JNEUROSCI.1676-11.2012] [PMID: 22357853]
[15]
Salloway, S.; Sperling, R.; Gilman, S.; Fox, N.C.; Blennow, K.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Doody, R.; van Dyck, C.H.; Mulnard, R.; Barakos, J.; Gregg, K.M.; Liu, E.; Lieberburg, I.; Schenk, D.; Black, R.; Grundman, M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology, 2009, 73(24), 2061-2070.
[http://dx.doi.org/10.1212/WNL.0b013e3181c67808] [PMID: 19923550]
[16]
Rinne, J.O.; Brooks, D.J.; Rossor, M.N.; Fox, N.C.; Bullock, R.; Klunk, W.E.; Mathis, C.A.; Blennow, K.; Barakos, J.; Okello, A.A. de LIano, S.R.M.; Liu, E.; Koller, M.; Gregg, K.M.; Schenk, D.; Black, R.; Grundman, M. 11C-PiB PET assessment of change in fibrillar amyloid-β load in patients with Alzheimer’s disease treated with bapineuzumab: A phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol., 2010, 9(4), 363-372.
[http://dx.doi.org/10.1016/S1474-4422(10)70043-0] [PMID: 20189881]
[17]
Black, R.S.; Sperling, R.A.; Safirstein, B.; Motter, R.N.; Pallay, A.; Nichols, A.; Grundman, M. A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2010, 24(2), 198-203.
[http://dx.doi.org/10.1097/WAD.0b013e3181c53b00] [PMID: 20505438]
[18]
Salloway, S.; Sperling, R.; Fox, N.C.; Blennow, K.; Klunk, W.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Porsteinsson, A.P.; Ferris, S.; Reichert, M.; Ketter, N.; Nejadnik, B.; Guenzler, V.; Miloslavsky, M.; Wang, D.; Lu, Y.; Lull, J.; Tudor, I.C.; Liu, E.; Grundman, M.; Yuen, E.; Black, R.; Brashear, H.R. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N. Engl. J. Med., 2014, 370(4), 322-333.
[http://dx.doi.org/10.1056/NEJMoa1304839] [PMID: 24450891]
[19]
Arai, H.; Umemura, K.; Ichimiya, Y.; Iseki, E.; Eto, K.; Miyakawa, K.; Kirino, E.; Shibata, N.; Baba, H.; Tsuchiwata, S. 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, 16(5), 644-650.
[http://dx.doi.org/10.1111/ggi.12516] [PMID: 26044070]
[20]
Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; Chou, R.; Glanville, J.; Grimshaw, J.M.; Hróbjartsson, A.; Lalu, M.M.; Li, T.; Loder, E.W.; Mayo-Wilson, E.; McDonald, S.; McGuinness, L.A.; Stewart, L.A.; Thomas, J.; Tricco, A.C.; Welch, V.A.; Whiting, P.; Moher, D. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 2021, 372(71), n71.
[http://dx.doi.org/10.1136/bmj.n71] [PMID: 33782057]
[21]
Institute of Medicine (US) Council on Health Care Technology; Goodman C, editor. Medical Technology Assessment Directory: A Pilot Reference To Organizations, Assessments, and Information Resources. Washington (DC): National Academies Press (US); 1988. National Heart, Lung, and Blood Institute. Available from: https://www.ncbi.nlm.nih.gov/books/NBK218529/
[22]
Review Manager (RevMan) [Computer program]. Version 5.4. 2021. https://training.cochrane.org/online-learning/core-software/revman/revman-5-download Accessed on 22 May 2022
[23]
Kerchner, G.A.; Boxer, A.L. Bapineuzumab. Expert Opin. Biol. Ther., 2010, 10(7), 1121-1130.
[http://dx.doi.org/10.1517/14712598.2010.493872] [PMID: 20497044]
[24]
Abushouk, A.I.; Elmaraezy, A.; Aglan, A.; Salama, R.; Fouda, S.; Fouda, R.; AlSafadi, A.M. Bapineuzumab for mild to moderate Alzheimer’s disease: A meta-analysis of randomized controlled trials. BMC Neurol., 2017, 17(1), 66.
[http://dx.doi.org/10.1186/s12883-017-0850-1] [PMID: 28376794]
[25]
Lu, L.; Zheng, X.; Wang, S.; Tang, C.; Zhang, Y.; Yao, G.; Zeng, J.; Ge, S.; Wen, H.; Xu, M.; Guyatt, G.; Xu, N. Anti-Aβ agents for mild to moderate Alzheimer’s disease: Systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry, 2020, 91(12), 1316-1324.
[http://dx.doi.org/10.1136/jnnp-2020-323497] [PMID: 33046560]
[26]
Srivastava, R.; Kumar, A. Use of aspirin in reduction of mortality of COVID‐19 patients: A meta‐analysis. Int. J. Clin. Pract., 2021, 75(11), e14515.
[http://dx.doi.org/10.1111/ijcp.14515] [PMID: 34118111]
[27]
D, V.; Sharma, A.; Kumar, A.; Flora, S.J.S. Neurological manifestations in COVID-19 patients: A meta-analysis. ACS Chem. Neurosci., 2021, 12(15), 2776-2797.
[http://dx.doi.org/10.1021/acschemneuro.1c00353] [PMID: 34260855]

Rights & Permissions Print Cite
Article Metrics
36
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy