Подходы к назначению антиангиогенных препаратов при терапии пациентов с неоваскулярной возрастной макулярной дегенерацией

Статья; ОбзорРОС ОФТАЛЬМОЛ ЖУР. 2019; Т. 12, № 3: 102–112. DOI:10.21516/2072-0076-2019-12-3-102-112

Иошин И.Э.^[1]

Аноприева Т.А.^[2]

^[1]Клиническая больница УДП РФ

^[2]«Байер»

Возрастная макулярная дегенерация (ВМД) — хроническое прогрессирующее заболевание, являющееся основной причиной инвалидности по зрению среди пациентов старшей возрастной группы в индустриально развитых странах. При этом наибольшим риском потери зрения характеризуется неоваскулярная ВМД. Стандартом терапии этого заболевания в настоящее время признано интравитреальное введение ингибиторов ангиогенеза. Показано, что применение ингибиторов ангиогенеза позволяет добиться стабилизации зрительных функций в более чем 90 [%] случаев и улучшения зрения на 3 строки и более (15 букв по шкале ETDRS) у 30–40 [%] пациентов. Тем не менее результаты наблюдательных исследований свидетельствуют о существовании барьеров, препятствующих эффективному проведению антиангиогенной терапии в условиях рутинной клинической практики. Одним из возможных путей преодоления данных барьеров является поиск оптимального режима назначения ингибиторов ангиогенеза, позволяющего уменьшить число необходимых инъекций без потери терапевтической эффективности. В обзоре рассмотрена текущая доказательная база, посвященная принципам назначения антиVEGF препаратов при лечении пациентов с неоваскулярной ВМД, проанализированы используемые в практике режимы дозирования с учетом их преимуществ и недостатков.

ингибиторы ангиогенеза

анти-VEGF

ранибизумаб

режимы дозирования

режим «по необходимости»

«лечить и увеличивать интервал»

«лечи и продлевай»

возрастная макулярная дегенерация

антиангиогенная терапия

анти-VEGF

афлиберцепт

миопическая хориоидальная неоваскуляризация

режимы дозирования

диабет

Pro Re Nata

Аветисов С.Е., Егоров Е.А., Мошетова Л.К., Нероев В.В., Тахчиди Х.П., ред. Офтальмология: национальное руководство. 2-е изд. Москва: ГЕОТАР-Медиа; 2018.

Wykoff C.C., Clark W.L., Nielsen J.S., et al. Optimizing anti-VEGF treatment outcomes for patients with neovascular age-related macular degeneration. J. Manag. Care Spec. Pharm. 2018 Feb; 24(2-a Suppl): S3-S15. doi: 10.18553/jmcp.2018.24.2-a.s3.
DOI: 10.18553/jmcp.2018.24.2-a.s3

Wong W.L., Su X., Li X., et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob. Health. 2014 Feb; 2 (2):e106-16. doi: 10.1016/S2214-109X(13)70145-1.
DOI: 10.1016/S2214-109X(13)70145-1

Ferrara N. Vascular endothelial growth factor and age-related macular degeneration: from basic science to therapy. Nat. Med. 2010 Oct; 16( 10): 1107–11. doi: 10.1038/nm1010-1107.
DOI: 10.1038/nm1010-1107

Ferrara N., Gerber H.P., Le Couter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun; 9 (6): 669–76. doi: 10.1038/ nm0603-669.
DOI: 10.1038/ nm0603-669

American Academy of Ophthalmology. Retina/Vitreous Panel. Preferred Practice Pattern Guidelines. Age-related Macular Degeneration. San Francisco, CA: American Academy of Ophthalmology. Updated 2015. Available at: https://www.aao.org/ preferred-practice-pattern/age-related-macular-degenerationppp-2015https://www.aao.org/

Schmidt-Erfurth U., Chong V., Loewenstein A., et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br. J. Ophthalmol. 2014 Sep; 98 (9): 1144–67. doi: 10.1136/ bjophthalmol-2014-305702.
DOI: 10.1136/ bjophthalmol-2014-305702

Возрастная макулярная дегенерация. Клинические рекомендации; 2017. Доступно на http://avo-portal.ru/doc/fkr/ approved/item/261-vozrastnaya-makulyarnaya-degeneratsiyahttp://avo-portal.ru/doc/fkr/

Возрастная макулярная дегенерация. Клинические рекомендации; 2017. Доступно на http://avo-portal.ru/doc/fkr/ approved/item/261-vozrastnaya-makulyarnaya-degeneratsiyahttp://avo-portal.ru/doc/fkr/approved/item/261vozrastnaya-makulyarnaya-degeneratsiya

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 Jun;15 (2): 171–85. doi: 10.1007/s10456-0119249-6.
DOI: 10.1007/s10456-0119249-6

Иошин И.Э. Безопасность интравитреальных инъекций. Офтальмохирургия. 2017; 3: 71–9..
DOI: 10.25276/0235-4160-2017-3-71-79

Holash J., Davis S., Papadopoulos N., et al. VEGF-Trap: a VEGF blocker with potent antitumor effects. In: Proc. of the National Academy of Sciences of the USA. 2002; 99 (17): 11393–8. https:// doi.org/10.1073/pnas.172398299.
DOI: 10.1073/pnas.172398299

Brown D.M., Kaiser P.K., Michels M., et al. Ranibizumab versus Verteporfin for neovascular age-related macular degeneration. New England Journal of Medicine. 2006; 355: 1432–44. https:// doi.org/10.1056/nejmoa062655.
DOI: 10.1056/nejmoa062655

Rosenfeld P.J., Brown D.M., Jeffrey S.H., et al. Ranibizumab for neovascular age-related macular degeneration. New England Journal of Medicine. 2006; 355: 1419–31. https://doi.org/10.1056/ nejmoa054481.
DOI: 10.1056/ nejmoa054481

Heier J.S., Brown D.M., Chong V., et al. Intravitreal Aflibercept (VEGF Trap-Eye) in wet age-related macular degeneration. Ophthalmology. 2012; 119: 2537–48. https://doi.org/10.1016/j. ophtha.2012.09.006.
DOI: 10.1016/j. ophtha.2012.09.006

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. Ophthalmology Retina. 2018; 2: 539–49. https://doi.org/10.1016/j. oret.2017.09.017.
DOI: 10.1016/j. oret.2017.09.017

Eleftheriadou M., Vazquez-Alfageme C., Citu C.M., et al. Long-term outcomes of Aflibercept treatment for neovascular age-related macular degeneration in a clinical setting. American Journal of Ophthalmology. 2017; 174: 160–8. https://doi.org/10.1016/j. ajo.2016.09.038.
DOI: 10.1016/j. ajo.2016.09.038

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.
DOI: 10.1097/ iae.0000000000000978

Talks J.S., Lotery A.J., Ghanchi F., et al. First-year visual acuity outcomes in the United Kingdom of providing aflibercept according to the VIEW study protocol for age-related macular degeneration. Ophthalmology. 2016 Feb; 123 (2): 337–43. doi: 10.1016/j. ophtha.2015.09.039.
DOI: 10.1016/j. ophtha.2015.09.039

Almuhtaseb H., Kanavati S., Rufai S.R., Lotery A.J. One-year realworld outcomes in patients receiving fixed dosing aflibercept for neovascular age-related macular degeneration. Eye (Lond). Eye (Lond). 2017 Jun; 31 (6): 878–83. doi: 10.1038/eye.2017.6.
DOI: 10.1038/eye.2017.6

Regillo C.D., Brown D.M., Abraham P., et al. Randomized, doublemasked, sham-controlled trial of Ranibizumab for neovascular age-related macular degeneration. Am. J. Ophthalmol. 2008; 145: 239–48. https://doi.org/10.1016/j.ajo.2007.10.004.
DOI: 10.1016/j.ajo.2007.10.004

Schmidt-Erfurth U., Eldem B., Guymer R., et al. Efficacy and safety of monthly versus quarterly Ranibizumab treatment in neovascular age related macular degeneration. Ophthalmology. 2011; 118: 831–9. https://doi.org/10.1016/j.ophtha.2010.09.004.
DOI: 10.1016/j.ophtha.2010.09.004

Garcia-Layana A., Figueroa M.S., Araiz J., et al. Treatment of exudative age-related macular degeneration: focus on Aflibercept. Drugs Aging. 2015; 32: 797–807. https://doi.org/10.1007/s40266-015-0300-y.
DOI: 10.1007/s40266-015-0300-y

Rezaei K.A., Stone T.W., eds. Global trends in retina survey. Chicago: American Society of Retina Specialists; 2015.

Fung A.E., Lalwani G.A., Rosenfeld P.J. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am. J. Ophthalmol. 2007 Apr; 143 (4): 566–83. doi: 10.1016/j.ajo.2007.01.028.
DOI: 10.1016/j.ajo.2007.01.028

Holz F.G., 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. doi: 10.1016/j.ophtha.2010.12.019.
DOI: 10.1016/j.ophtha.2010.12.019

Boyer D.S., Heier J.S., Brown D.M., et al. A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. Ophthalmology. 2009; 116 (9): 1731–9. doi: 10.1016/j.ophtha.2009.05.024.
DOI: 10.1016/j.ophtha.2009.05.024

CATT Research Group. (2011). Ranibizumab and bevacizumab for neovascular age-related macular degeneration. New England Journal of Medicine. 364 (20): 1897–908.

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.

Братко Г.В., Смирнов Е.В., Трунов А.Н., Черных В.В. Практика применения анти-VEGF терапии в России: результаты онлайн-опроса. Современные технологии в офтальмологии. 2015; 1: 39. Доступно на: https://eyepress.ru/article.aspx?16351https://eyepress.ru/article.aspx?16351

Holz F.G., 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): 220–6. doi: 10.1136/bjophthalmol-2014-305327.
DOI: 10.1136/bjophthalmol-2014-305327

Muether P.S., Hoerster R., Hermann M.M., 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. doi: 10.1007/s00417-012-2038-0.
DOI: 10.1007/s00417-012-2038-0

Lanzetta P., Loewenstein A. Vision Academy Steering Committee. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases. Graefes Arch. Clin. Exp. Ophthalmol. 2017 Jul; 255 (7): 1259–73. doi: 10.1007/s00417017-3647-4.
DOI: 10.1007/s00417017-3647-4

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 Mar; 251 (3): 697–704. doi: 10.1007/ s00417-012-2090-9.
DOI: 10.1007/ s00417-012-2090-9

Muether P.S., Hermann M.M., Dröge 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 Nov; 156 (5): 989–93.e2. doi: 10.1016/j. ajo.2013.06.020.
DOI: 10.1016/j. ajo.2013.06.020

Fauser S., Schwabecker V., Muether P.S. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am. J. Ophthalmol. 2014 Sep; 158 (3): 532–6. doi: 10.1016/j.ajo.2014.05.025.
DOI: 10.1016/j.ajo.2014.05.025

Fauser S., Muether P.S. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br. J .Ophthalmol. 2016 Nov; 100 (11): 1494–8. doi: 10.1136/bjophthalmol-2015-308264.
DOI: 10.1136/bjophthalmol-2015-308264

Berg K., Pedersen T.R., 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): 146–52. doi: 10.1016/j.ophtha. 2014.07.041.
DOI: 10.1016/j.ophtha. 2014.07.041

Wykoff C.C., Croft D.E., Brown D.M., et al. Prospective trial of Treat-and- Extend versus Monthly Dosing for neovascular age-related macular degeneration: TREX-AMD 1-year results. Ophthalmology. 2015; 122 (12): 2514–22. doi: 10.1016/j. ophtha.2015.08.009.
DOI: 10.1016/j. ophtha.2015.08.009

Silva R., Berta A., Larsen M., et al. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: results with ranibizumab from the TREND study. Ophthalmology. 2018 Jan; 125 (1): 57–65. doi: 10.1016/j.ophtha.2017.07.014.
DOI: 10.1016/j.ophtha.2017.07.014

Kertes P.J., Galic I.J., Greve M., et al. Canadian Treat-and-Extend analysis trial with ranibizumab in patients with neovascular age-related macular disease: one-year results of the randomized Canadian Treat-and-Extend analysis trial with ranibizumab study. Ophthalmology. 2019 Jun; 126 (6): 841–8. doi: 10.1016/j. ophtha.2019.01.013.
DOI: 10.1016/j. ophtha.2019.01.013

Okada A.A., Takahashi K. Use of intravitreal Aflibercept Treat and-Extend dosing for wet age-related macular degeneration: 52-week ALTAIR results. In: Proc. of the American Academy of Ophthalmology (AAO) Congress; 2017 Nov 11–14; New Orleans, LA, USA. Доступно по: https://aao.scientificposters.com/ epsAbstractAAO.cfm?id=1https://aao.scientificposters.com/

Gillies M.C., Hunyor A.P., Arnold J., et al. Effect of Ranibizumab and Aflibercept on best-corrected visual acuity in Treat-and-Extend for neovascular age-related macular degeneration: a randomized clinical trial. JAMA ophthalmology. 2019 Jan; 24: 372–9. https:// doi.org/10.1001/jamaophthalmol.2018.6776.
DOI: 10.1001/jamaophthalmol.2018.6776

Ying G.S., Huang J., Maguire M. G., et al. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration. Ophthalmology. 2013 Jan; 120 (1): 122–9. doi: 10.1016/j.ophtha.2012.07.042.
DOI: 10.1016/j.ophtha.2012.07.042

Lim J.H., Wickremasinghe S. S., Xie J., et al. Delay to treatment and visual outcomes in patients treated with anti-vascular endothelial growth factor for age-related macular degeneration. Am. J. Ophthalmol. 2012 Apr; 153 (4): 678–86, 686.e1-2. doi: 10.1016/j.ajo.2011.09.013.
DOI: 10.1016/j.ajo.2011.09.013

Singer M.A., Awh C.C., Sadda S., et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012 Jun; 119 (6): 1175–83. doi: 10.1016/j.ophtha.2011.12.016.
DOI: 10.1016/j.ophtha.2011.12.016

Kaiser P.K., Singer M., Tolentino M., et al. Long-term safety and visual outcome of intravitreal aflibercept in neovascular age-related macular degeneration. VIEW 1 extension study. Ophthalmology. 2017 Aug; 128 (8): 1090–5. https://doi. org/10.1016/j.oret.2017.01.004.
DOI: 10.1016/j.oret.2017.01.004

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 Jan; 123 (1): 51–9. doi: 10.1016/j.ophtha.2015.09.018.
DOI: 10.1016/j.ophtha.2015.09.018

Wykoff C.C., Ou W.C., Brown D.M. Randomized trial of treatand-extend versus monthly dosing for neovascular age-related macular degeneration: 2-year results of the TREX-AMD study. Ophthalmology Retina. 2017 July-August; 1 (4): 314–21. https:// doi.org/10.1016/j.oret.2016.12.004.
DOI: 10.1016/j.oret.2016.12.004

Ohji M., Ayame A., Takahashi K. Two different treat-and-extend dosing regimens of intravitreal aflibercept in Japanese patients with wet age-related macular degeneration: 96-week results of the ALTAIR study. Presented at 18th EURETINA congress, VIenna, 09.2018 Доступно по: http://abstracts.euretina.org/http://abstracts.euretina.org/

Mekjavić P. J., Gregorčič B., Oberč C., Podgoršek S. Treat-andextend therapy using intravitreal aflibercept for neovascular agerelated macular degeneration: 2-year real-world practice data from Slovenia. BMC Ophthalmol. 2018 Dec 20; 18 (1): 333. doi: 10.1186/ s12886-018-1005-x.
DOI: 10.1186/ s12886-018-1005-x

Язык текста: Русский

ISSN: 2072-0076