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


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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.

About the authors

Yaqi Gao

College of Nursing, Hebi Polytechnic

Author for correspondence.
Email: info@benthamscience.net

Jing Guo

College of Nursing, Hebi Polytechnic

Email: info@benthamscience.net

Fang Zhang

College of Nursing, Hebi Polytechnic

Email: info@benthamscience.net

Yanfang Li

College of Nursing, Hebi Polytechnic, Hebi

Email: info@benthamscience.net

References

  1. Goedert, M.; Spillantini, M.G. A century of Alzheimer’s disease. Science, 2006, 314(5800), 777-781. doi: 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. doi: 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. doi: 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. doi: 10.1097/NEN.0b013e31825018f7
  5. Thies, W.; Bleiler, L. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement., 2013, 9(2), 208-245. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1021/acschemneuro.1c00353 PMID: 34260855

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