Ziv-aflibercept in macular disease

Ahmad M Mansour, Sara I Al-Ghadban, Muhammad H Yunis, Marwan E El-Sabban, Ahmad M Mansour, Sara I Al-Ghadban, Muhammad H Yunis, Marwan E El-Sabban

Abstract

Background/aims: Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis.

Methods: Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA.

Results: There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab.

Conclusions: Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept.

Trial registration number: NCT02173873.

Keywords: Angiogenesis; Drugs; Macula; Neovascularisation.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

References

    1. Schmid MK, Bachmann LM, Fäs L, et al. . Efficacy and adverse events of aflibercept, ranibizumab and bevacizumab in age-related macular degeneration: a trade-off analysis. Br J Ophthalmol 2015;99:141–6. 10.1136/bjophthalmol-2014-305149
    1. Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. . Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology 2014;121:193–201. 10.1016/j.ophtha.2013.08.011
    1. Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. . Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014;121:2247–54. 10.1016/j.ophtha.2014.05.006
    1. Jeng KW, Wilgucki J, Halperin S, et al. . Retina specialists treating age-related macular degeneration recommend different approaches for patients than they would choose for themselves. Retina 2014;34:1796–801. 10.1097/IAE.0000000000000182
    1. Silver J. Drugs for macular degeneration, price discrimination, and Medicare's responsibility not to overpay. JAMA 2014;312:23–4. 10.1001/jama.2014.6672
    1. Trichonas G, Kaiser PK. Aflibercept for the treatment of age-related macular degeneration. Ophthalmol Ther 2013;2:89–98. 10.1007/s40123-013-0015-2
    1. Ng DS, Kwok AK, Chan CW, et al. . Intravitreal bevacizumab: safety of multiple doses from a single vial for consecutive patients. Hong Kong Med J 2012;18:488–95.
    1. Chen YH, Wu PC, Shiea J, et al. . Evaluation of the sterility, stability, and efficacy of bevacizumab stored in multiple-dose vials for 6 months. J Ocul Pharmacol Ther 2009;25:65–9. 10.1089/jop.2008.0043
    1. Ornek K, Karahan ZC, Ergin A, et al. . Bevacizumab sterility in multiple doses from a single-use vial. Ann Pharmacother 2008;42:1425–8. 10.1345/aph.1L270
    1. Marmor MF, Martin LJ, Tharpe S. Osmotically induced retinal detachment in the rabbit and primate. Electron miscoscopy of the pigment epithelium. Invest Ophthalmol Vis Sci 1980;19:1016–29.
    1. Sturner WQ, Dowdey AB, Putnam RS, et al. . Osmolality and other chemical determinations in postmortem human vitreous humor. J Forensic Sci 1972;17:387–93.
    1. Gagajewski A, Murakami MM, Kloss J, et al. . Measurement of chemical analytes in vitreous humor: Stability and precision studies. J Forensic Sci 2004;49:371–4. 10.1520/JFS2003152
    1. Malik D, Tarek M, Caceres del Carpio J, et al. . Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture. Br J Ophthalmol 2014;98(Suppl 1):i11–16. 10.1136/bjophthalmol-2014-305302
    1. Klettner A, Tahmaz N, Dithmer M, et al. . Effects of aflibercept on primary RPE cells: toxicity, wound healing, uptake and phagocytosis. Br J Ophthalmol 2014;98:1448–52. 10.1136/bjophthalmol-2014-305105
    1. de Oliveira Dias JR, Badaró E, Novais EA, et al. . Preclinical investigations of intravitreal ziv-aflibercept. Ophthalmic Surg Lasers Imaging Retina 2014;45: 577–84. 10.3928/23258160-20141118-15
    1. Rosenfeld PJ. Intravitreal avastin: the low cost alternative to lucentis? Am J Ophthalmol 2006;142:141–3. 10.1016/j.ajo.2006.03.036
    1. Stein JD, Newman-Casey PA, Mrinalini T, et al. . Cost-effectiveness of bevacizumab and ranibizumab for newly diagnosed neovascular macular degeneration. Ophthalmology 2014;121:936–45. 10.1016/j.ophtha.2013.10.037
    1. Raftery J, Clegg A, Jones J, et al. . Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost effectiveness. Br J Ophthalmol 2007;91:1244–6. 10.1136/bjo.2007.116616
    1. Yannuzzi NA, Klufas MA, Quach L, et al. . Evaluation of compounded bevacizumab prepared for intravitreal injection. JAMA Ophthalmol 2015;133:32–9. 10.1001/jamaophthalmol.2014.3591
    1. Paul M, Vieillard V, Roumi E, et al. . Long-term stability of bevacizumab repackaged in 1 mL polypropylene syringes for intravitreal administration. Ann Pharm Fr 2012;70:139–54. 10.1016/j.pharma.2012.03.006
    1. Signorello L, Pucciarelli S, Bonacucina G, et al. . Quantification, microbial contamination, physico-chemical stability of repackaged bevacizumab stored under different conditions. Curr Pharm Biotechnol 2014;15:113–19. 10.2174/1389201015666140619120834
    1. Palmer JM, Amoaku WM, Kamali F. Quality of bevacizumab compounded for intravitreal administration. Eye 2013;27:1090–7. 10.1038/eye.2013.139
    1. Thomas M, Mousa SS, Mousa SA. Comparative effectiveness of aflibercept for the treatment of patients with neovascular age-related macular degeneration. Clin Ophthalmol 2013;7:495–501.
    1. Ahn SJ, Ahn J, Park S, et al. . Intraocular pharmacokinetics of ranibizumab in vitrectomized versus nonvitrectomized eyes. Invest Ophthalmol Vis Sci 2014;55:567–73. 10.1167/iovs.13-13054
    1. Moisseiev E, Waisbourd M, Ben-Artsi E, et al. . Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefes Arch Clin Exp Ophthalmol 2014;252:331–7. 10.1007/s00417-013-2495-0
    1. Hahn P, Kim JE, Stinnett S, et al. . Aflibercept-related sterile inflammation. Ophthalmology 2013;120:1100–1. 10.1016/j.ophtha.2012.11.018
    1. Bailey C, Aloumanis V, Walker B, et al. . Stability of preoperative cataract surgery gel in polycarbonate syringes. Int J Pharm Compd 2009;13:564–8.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel