Dosing regimens of angiogenesis inhibitors in the treatment of neovascular age-related macular degeneration patients

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Abstract

The literature review compares the data on different dosing regimens of angiogenesis inhibitors in the treatment of neovascular age-related macular degeneration patients. Clinical approaches to the repeated intravitreal angiogenesis inhibitors dosing are described, the results of key clinical trials on the effectiveness of various drugs used in different dosing regimens are presented, positive and negative aspects of each of discussed treatment regimens are specified.

About the authors

Yury S. Astakhov

Pavlov First Saint Petersburg State Medical University

Email: astakhov73@mail.ru
SPIN-code: 7164-4749
Scopus Author ID: 100400235000040023500
ResearcherId: p-1322-2017

MD, PhD, DMedSc, Professor, Department of Ophthalmo­logy

Russian Federation, Saint Petersburg

Pavel A. Nechiporenko

Pavlov First Saint Petersburg State Medical University

Author for correspondence.
Email: paul_because@mail.ru
ORCID iD: 0000-0002-1604-2569
SPIN-code: 5284-7182

MD, PhD, Assistant, Department of Ophthalmo­logy

Russian Federation, Saint Petersburg

References

  1. World Health Organization. Vision 2020. Global initiative for the elimination of avoidable blindness. Geneva: WHO; 2007.
  2. Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15(2):171-185. https://doi.org/10.1007/s10456-011-9249-6.
  3. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419-1431. https://doi.org/10.1056/NEJMoa054481.
  4. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432-1444. https://doi.org/10.1056/NEJMoa062655.
  5. Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015;99(2):220-226. https://doi.org/10.1136/bjophthalmol-2014-305327.
  6. Wolf A, Kampik A. Efficacy of treatment with ranibizumab in patients with wet age-related macular degeneration in routine clinical care: data from the COMPASS health services research. Graefes Arch Clin Exp Ophthalmol. 2014;252(4):647-655. https://doi.org/10.1007/s00417-013-2562-6.
  7. Mitchel P, Ziemssen F, Scheidow T, et al. Visual acuity outcomes in patients with diabetic macular edema treated with ranibizumab in real-life setting: Results from the final analysis of the LUMINOUS study. In: Proceedings of the 17th EURETINA Congress; 2017 Sep 9; Barcelona, Spain.
  8. Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008;145(2):239-248. https://doi.org/10.1016/j.ajo.2007.10.004.
  9. Schmidt-Erfurth U, Eldem B, Guymer R, et al. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmo¬logy. 2011;118(5):831-839. https://doi.org/10.1016/j.ophtha.2010.09.004.
  10. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. https://doi.org/10.1016/j.ophtha.2012.09.006.
  11. Talks JS, Lotery AJ, Ghanchi F, et al. First-Year Visual Acuity Outcomes of Providing Aflibercept According to the VIEW Study Protocol for Age-Related Macular Degeneration. Ophthalmology. 2016;123(2):337-343. https://doi.org/10.1016/j.ophtha.2015.09.039.
  12. Eleftheriadou M, Vazquez-Alfageme C, Citu CM, et al. Long-Term Outcomes of Aflibercept Treatment for Neovascular Age-Related Macular Degeneration in a Clinical Setting. Am J Ophthalmol. 2017;174:160-168. https://doi.org/10.1016/j.ajo.2016.09.038.
  13. Framme C, Eter N, Hamacher T, et al. Aflibercept for Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice in Germany: Twelve-Month Outcomes of PERSEUS. Ophthalmol Retina. 2018;2(6):539-549. https://doi.org/10.1016/j.oret.2017.09.017.
  14. Almuhtaseb H, Kanavati S, Rufai SR, Lotery AJ. One-year real-world outcomes in patients receiving fixed-dosing aflibercept for neovascular age-related macular degeneration. Eye (Lond). 2017;31(6):878-883. https://doi.org/10.1038/eye.2017.6.
  15. Epstein D, Amren U. Near Vision Outcome in Patients with Age-Related Macular Degeneration Treated with Aflibercept. Retina. 2016;36(9):1773-7. https://doi.org/10.1097/IAE.0000000000000978.
  16. Lalwani GA, Rosenfeld PJ, Fung AE, et al. A variable-dosing regimen with intravitreal ranibizumab for neovascular age-related macular degeneration: year 2 of the PrONTO Study. Am J Ophthalmol. 2009;148(1):43-58 e41. https://doi.org/10.1016/j.ajo.2009.01.024.
  17. Holz FG, Amoaku W, Donate J, et al. Safety and efficacy of a flexible dosing regimen of ranibizumab in neovascular age-related macular degeneration: the SUSTAIN study. Ophthalmology. 2011;118(4): 663-71. https://doi.org/10.1016/j.ophtha.2010.12.019.
  18. Boyer DS, Heier JS, Brown DM, et al. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009;116(9):1731-1739. https://doi.org/10.1016/j.ophtha.2009.05.024.
  19. Singer MA, Awh CC, Sadda S, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119(6):1175-83. https://doi.org/10.1016/j.ophtha.2011.12.016.
  20. Muether PS, Hoerster R, Hermann MM, et al. Long-term effects of ranibizumab treatment delay in neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2013;251(2):453-8. https://doi.org/10.1007/s00417-012-2038-0.
  21. Mori R, Tanaka K, Haruyama M, et al. Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration. Ophthalmologica. 2017;238(1-2):17-22. https://doi.org/10.1159/000468950.
  22. Mantel I, Deli A, Iglesias K, Ambresin A. Prospective study evaluating the predictability of need for retreatment with intravitreal ranibizumab for age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2013;251(3):697-704. https://doi.org/10.1007/s00417-012-2090-9.
  23. Muether PS, Hermann MM, Droge K, et al. Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration. Am J Ophthalmol. 2013;156(5):989-993 e982. https://doi.org/10.1016/j.ajo.2013.06.020.
  24. Global Trends in Retina Survey. Ed. by K.A. Rezaei, T.W. Stone. Chicago: American Society of Retina Specialists; 2015.
  25. Berg K, Pedersen TR, Sandvik L, Bragadottir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015;122(1):146-152. https://doi.org/10.1016/j.ophtha.2014.07.041.
  26. Berg K, Hadzalic E, Gjertsen I, et al. Ranibizumab or Bevacizumab for Neovascular Age-Related Macular Degeneration According to the Lucentis Compared to Avastin Study Treat-and-Extend Protocol: Two-Year Results. Ophthalmology. 2016;123(1):51-59. https://doi.org/10.1016/j.ophtha.2015.09.018.
  27. Wykoff CC, Croft DE, Brown DM, et al. Prospective Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Rela¬ted Macular Degeneration: TREX-AMD 1-Year Results. Ophthalmo¬logy. 2015;122(12):2514-2522. https://doi.org/10.1016/j.ophtha.2015.08.009.
  28. Ohji M. Two different Treat and Extend dosing regimens of intravitreal aflibercept for wAMD in Japanese patients: 52 weeks results of the ALTAIR study. In: Proceedings of the 17th EURETINA Congress; 2017 Sep 9; Barcelona, Spain.
  29. Okada AA, Takahashi K. Use of Intravitreal Aflibercept Treat-and-Extend Dosing for Wet Age-Related Macular Degeneration: 52-Week ALTAIR Results. In: Proceedings of the American Aca¬demy of Ophthalmology (AAO) Congress; 2017 Nov 11-14; New Orleans, LA, USA.
  30. Fauser S, Schwabecker V, Muether PS. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol. 2014;158(3):532-536. https://doi.org/10.1016/j.ajo.2014.05.025.
  31. Fauser S, Muether PS. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol. 2016;100(11):1494-1498. https://doi.org/10.1136/bjophthalmol-2015-308264.

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2. Fig. 1. Regimens of anti-VEGF therapy: а – the fixed regimen includes monthly monitoring visits, on each of which patient is being injected; b – fixed mode with a frequency of injections of 1 every 2 months. After 3 monthly loading injections, the interval between visits, on which the injection is made increases to 2 months; c – PRN (Pro re Nata) involves the injection of necessity. After the end of the loading phase, the frequency of monitoring visits continues on a monthly basis, with decision making about inject or not on each of them; d – Treat & Extend therapy regimen (T & E) is based on an individual approach to disease activity. After the loading phase, the intervals between exams, each of which is accompanies with injection, increase for a certain period, for example 2 weeks. After determining the maximum possible interval between injections, the patient continues therapy in this mode. If the patient shows a return of the disease activity, the intervals between injections should be shorten accordingly. The image reflects the treatment regimen scheme with the stepwise interval extension

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Copyright (c) 2019 Astakhov Y.S., Nechiporenko P.A.

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This work is licensed under a Creative Commons Attribution 4.0 International License.
 


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