EFFICACY AND SAFETY OF INTRAVITREAL AFLIBERCEPT USING A TREAT-AND-EXTEND REGIMEN FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: The ARIES Study: A Randomized Clinical Trial.
Aged
Aged, 80 and over
Angiogenesis Inhibitors
/ administration & dosage
Female
Follow-Up Studies
Humans
Intravitreal Injections
Macula Lutea
/ diagnostic imaging
Male
Middle Aged
Ranibizumab
/ administration & dosage
Receptors, Vascular Endothelial Growth Factor
/ administration & dosage
Recombinant Fusion Proteins
/ administration & dosage
Time Factors
Tomography, Optical Coherence
/ methods
Treatment Outcome
Vascular Endothelial Growth Factor A
/ antagonists & inhibitors
Visual Acuity
Wet Macular Degeneration
/ diagnosis
Journal
Retina (Philadelphia, Pa.)
ISSN: 1539-2864
Titre abrégé: Retina
Pays: United States
ID NLM: 8309919
Informations de publication
Date de publication:
01 Sep 2021
01 Sep 2021
Historique:
pubmed:
31
3
2021
medline:
7
1
2022
entrez:
30
3
2021
Statut:
ppublish
Résumé
Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start T&E was noninferior to late-start T&E. A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104. Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-T&E vs. late-T&E; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients. Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-T&E or late-T&E regimen after initial dosing, with one injection difference over 2 years. ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).
Sections du résumé
BACKGROUND/PURPOSE
OBJECTIVE
Treating neovascular age-related macular degeneration with intravitreal aflibercept treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether intravitreal aflibercept early-start T&E was noninferior to late-start T&E.
METHODS
METHODS
A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with the best-corrected visual acuity 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2 mg intravitreal aflibercept at Week (W) 0, W4, W8, and W16. At W16, patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: the best-corrected visual acuity change from randomization to W104.
RESULTS
RESULTS
Two-hundred seventy-one patients were randomized. The mean (SD) best-corrected visual acuity at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. The mean (SD) best-corrected visual acuity change (W16-104) was -2.1 (11.4) versus -0.4 (8.4) letters (early-T&E vs. late-T&E; least-squares mean difference: -2.0; 95% confidence interval: -4.75 to 0.71; P = 0.0162 for noninferior); +4.3 (13.4) versus +7.9 (11.9) letters (W0-104). The mean (SD) number of injections was 12.0 (2.3) versus 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained best-corrected visual acuity; the mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. The last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients.
CONCLUSION
CONCLUSIONS
Outcomes were similar between patients with neovascular age-related macular degeneration treated with an intravitreal aflibercept early-T&E or late-T&E regimen after initial dosing, with one injection difference over 2 years.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov Identifier: NCT02581891 https://clinicaltrials.gov/ct2/show/NCT02581891. Supplemental Digital Contents (files 1 http://links.lww.com/IAE/B419).
Identifiants
pubmed: 33782365
doi: 10.1097/IAE.0000000000003128
pii: 00006982-202109000-00015
pmc: PMC8384251
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Recombinant Fusion Proteins
0
Vascular Endothelial Growth Factor A
0
aflibercept
15C2VL427D
Receptors, Vascular Endothelial Growth Factor
EC 2.7.10.1
Ranibizumab
ZL1R02VT79
Banques de données
ClinicalTrials.gov
['NCT02581891']
Types de publication
Clinical Trial, Phase III
Clinical Trial, Phase IV
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1911-1920Commentaires et corrections
Type : ErratumIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.
Références
Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron 2012;75:26–39.
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;98:1144–1167.
Maguire MG, Martin DF, Ying GS, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology 2016;123:1751–1761.
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;255:1259–1273.
Freund KB, Korobelnik JF, Devenyi R, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases: a literature review and consensus recommendations. Retina 2015;35:1489–1506.
Patel PJ, Devonport H, Sivaprasad S, et al. Aflibercept treatment for neovascular AMD beyond the first year: consensus recommendations by a UK expert roundtable panel, 2017 update. Clin Ophthalmol 2017;11:1957–1966.
Chakravarthy U, Harding SP, Rogers CA, et al. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology 2012;119:1399–1411.
Giannakaki-Zimmermann H, Ebneter A, Munk MR, et al. Outcomes when switching from a pro re nata regimen to a treat and extend regimen using aflibercept in neovascular age-related macular degeneration. Ophthalmologica 2016;236:201–206.
Ohji M, Takahashi K, Okada AA, et al. Efficacy and safety of intravitreal aflibercept treat-and-extend regimens in exudative age-related macular degeneration: 52- and 96-week findings from ALTAIR. Adv Ther 2020;37:1173–1187.
Bayer. Eylea (Aflibercept) Summary of Product Characteristics. 2018. Available at: https://www.ema.europa.eu/en/documents/product-information/eylea-epar-product-information_en.pdf . Accessed April 9, 2021.
Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012;119:2537–2548.
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.
Do DV, Nguyen QD. Pharmacokinetics of free aflibercept in patients with neovascular age related macular degeneration. Invest Ophthalmol Vis Sci 2017;58:406.
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;158:532–536.
Fauser S, Muether PS. Clinical correlation to differences in ranibizumab and aflibercept vascular endothelial growth factor suppression times. Br J Ophthalmol 2016;100:1494–1498.
Khurana RN, Rahimy E, Joseph WA, et al. Extended (every 12 weeks or longer) dosing interval with intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration: post hoc analysis of VIEW trials. Am J Ophthalmol 2019;200:161–168.
Eleftheriadou M, Gemenetzi M, Lukic M, et al. Three-year outcomes of aflibercept treatment for neovascular age-related macular degeneration: Evidence from a clinical setting. Ophthalmol Ther 2018;7:361–8.
Kim LN, Mehta H, Barthelmes D, et al. Metaanalysis of real-world outcomes of intravitreal ranibizumab for the treatment of neovascular age-related macular degeneration. Retina 2016;36:1418–1431.
DeCroos FC, Reed D, Adam MK, et al. Treat-and-Extend therapy using aflibercept for neovascular age-related macular degeneration: a prospective clinical trial. Am J Ophthalmol 2017;180:142–150.
Gillies MC, Hunyor AP, Arnold JJ, 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 Ophthalmol 2019;137:372–379.