Intravitreal Aflibercept for the Treatment of Diabetic Macular Edema in Routine Clinical Practice: Results from the 24-Month AURIGA Observational Study.
Anti-vascular endothelial growth factor
Diabetes
Diabetic macular edema
Diabetic retinopathy
Intravitreal aflibercept
Observational study
Real-world evidence
Retinal disease
Journal
Ophthalmology and therapy
ISSN: 2193-8245
Titre abrégé: Ophthalmol Ther
Pays: England
ID NLM: 101634502
Informations de publication
Date de publication:
04 Nov 2023
04 Nov 2023
Historique:
received:
31
05
2023
accepted:
29
09
2023
medline:
4
11
2023
pubmed:
4
11
2023
entrez:
4
11
2023
Statut:
aheadofprint
Résumé
AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) in the treatment of diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion in routine clinical practice. The 24-month outcomes in the DME cohort from across 11 participating countries are reported here. AURIGA (NCT03161912) was a prospective observational study. The study enrolled eligible patients with DME for whom the decision to treat with IVT-AFL had previously been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month 12 (M12). All statistical analyses were descriptive. In 1478 treatment-naïve and 384 previously treated patients with DME, the mean (95% confidence interval) change in VA from baseline was +6.7 (5.7, 7.6) and +7.4 (5.5, 9.4) letters by M12 and +5.9 (4.9, 6.9) and +8.1 (6.1, 10.1) letters by M24 (baseline [mean ± standard deviation]: 56.0 ± 19.8 and 50.8 ± 19.5 letters), respectively; 25.9% of treatment-naïve and 32.8% of previously treated patients achieved ≥ 15-letter gains by M24. The mean change in central retinal thickness from baseline to M24 was -110 (-119, -102) µm in treatment-naïve patients and -169 (-188, -151) µm in previously treated patients. By M6, M12, and M24, treatment-naïve patients had received 3.8 ± 1.7, 4.9 ± 2.8, and 5.7 ± 3.9 injections, respectively, and previously treated patients had received 3.9 ± 1.5, 4.9 ± 2.4, and 6.2 ± 3.6 injections, respectively. The safety profile of IVT-AFL was consistent with previous studies. In AURIGA, treatment-naïve and previously treated patients with DME achieved clinically relevant functional and anatomic improvements following IVT-AFL treatment for up to 24 months in routine clinical practice. Even with the decreasing injection frequency observed, these gains were largely maintained throughout the study, suggesting long-term durability of the positive effects of IVT-AFL treatment. Infographic available for this article. ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.
Identifiants
pubmed: 37924483
doi: 10.1007/s40123-023-00829-3
pii: 10.1007/s40123-023-00829-3
doi:
Banques de données
ClinicalTrials.gov
['NCT03161912']
Types de publication
Journal Article
Langues
eng
Informations de copyright
© 2023. The Author(s).
Références
Im JHB, Jin YP, Chow R, Yan P. Prevalence of diabetic macular edema based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Surv Ophthalmol. 2022;67(4):1244–51.
doi: 10.1016/j.survophthal.2022.01.009
pubmed: 35093404
Schiefelbein J, Müller M, Kern C, Herold T, Liegl R, Fasler K, et al. Gender-related differences in patients treated with intravitreal anti-vascular endothelial growth factor medication for diabetic macular oedema. Eur J Ophthalmol. 2020;30(6):1410–7.
doi: 10.1177/1120672119899627
pubmed: 31937122
Browning DJ, Stewart MW, Lee C. Diabetic macular edema: evidence-based management. Indian J Ophthalmol. 2018;66(12):1736–50.
doi: 10.4103/ijo.IJO_1240_18
pubmed: 30451174
pmcid: 6256891
Zhang J, Zhang J, Zhang C, Zhang J, Gu L, Luo D, et al. Diabetic macular edema: current understanding, molecular mechanisms and therapeutic implications. Cells. 2022;11(21):3362.
doi: 10.3390/cells11213362
pubmed: 36359761
pmcid: 9655436
Daruich A, Matet A, Moulin A, Kowalczuk L, Nicolas M, Sellam A, et al. Mechanisms of macular edema: beyond the surface. Prog Retin Eye Res. 2018;63:20–68.
doi: 10.1016/j.preteyeres.2017.10.006
pubmed: 29126927
Uemura A, Fruttiger M, D’Amore PA, De Falco S, Joussen AM, Sennlaub F, et al. VEGFR1 signaling in retinal angiogenesis and microinflammation. Prog Retin Eye Res. 2021;84: 100954.
doi: 10.1016/j.preteyeres.2021.100954
pubmed: 33640465
pmcid: 8385046
Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis. 2012;15(2):171–85.
doi: 10.1007/s10456-011-9249-6
pubmed: 22302382
pmcid: 3338918
European Medicines Agency. Eylea Summary of product characteristics 2012 [updated January 2023; cited May 2023]. Available from: https://www.ema.europa.eu/en/documents/product-information/eylea-epar-product-information_en.pdf .
Food and Drug Administration. Eylea prescribing information 2011 [updated September 2022; cited May 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125387s076lbl.pdf .
Regeneron Pharmaceuticals, Inc. Eylea
Korobelnik JF, Do DV, Schmidt-Erfurth U, Boyer DS, Holz FG, Heier JS, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247–54.
doi: 10.1016/j.ophtha.2014.05.006
pubmed: 25012934
Brown DM, Schmidt-Erfurth U, Do DV, Holz FG, Boyer DS, Midena E, et al. Intravitreal aflibercept for diabetic macular edema: 100-week results from the VISTA and VIVID studies. Ophthalmology. 2015;122(10):2044–52.
doi: 10.1016/j.ophtha.2015.06.017
pubmed: 26198808
Heier JS, Korobelnik JF, Brown DM, Schmidt-Erfurth U, Do DV, Midena E, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies. Ophthalmology. 2016;123(11):2376–85.
doi: 10.1016/j.ophtha.2016.07.032
pubmed: 27651226
Burns L, Roux NL, Kalesnik-Orszulak R, Christian J, Hukkelhoven M, Rockhold F, et al. Real-world evidence for regulatory decision-making: guidance from around the world. Clin Ther. 2022;44(3):420–37.
doi: 10.1016/j.clinthera.2022.01.012
pubmed: 35181179
Daien V, Eldem BM, Talks JS, Korobelnik JF, Mitchell P, Finger RP, et al. Real-world data in retinal diseases treated with anti-vascular endothelial growth factor (anti-VEGF) therapy—a systematic approach to identify and characterize data sources. BMC Ophthalmol. 2019;19(1):206.
doi: 10.1186/s12886-019-1208-9
pubmed: 31619195
pmcid: 6796465
Klonoff DC. The new FDA real-world evidence program to support development of drugs and biologics. J Diabetes Sci Technol. 2020;14(2):345–9.
doi: 10.1177/1932296819832661
pubmed: 30862182
Gregori NZ, Feuer W, Rosenfeld PJ. Novel method for analyzing Snellen visual acuity measurements. Retina. 2010;30(7):1046–50.
doi: 10.1097/IAE.0b013e3181d87e04
pubmed: 20559157
Diabetic Retinopathy Clinical Research Network Writing Committee, Bressler SB, Edwards AR, Chalam KV, Bressler NM, Glassman AR, et al. Reproducibility of spectral-domain optical coherence tomography retinal thickness measurements and conversion to equivalent time-domain metrics in diabetic macular edema. JAMA Ophthalmol. 2014;132(9):1113–22.
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD, et al. Development of the 25-item national eye institute visual function questionnaire. Arch Ophthalmol. 2001;119(7):1050–8.
doi: 10.1001/archopht.119.7.1050
pubmed: 11448327
Yardley L, Beyer N, Hauer K, Kempen G, Piot-Ziegler C, Todd C. Development and initial validation of the Falls Efficacy Scale-International (FES-I). Age Ageing. 2005;34(6):614–9.
doi: 10.1093/ageing/afi196
pubmed: 16267188
Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.
doi: 10.1111/j.1600-0447.1983.tb09716.x
pubmed: 6880820
Submacular Surgery Trials Research Group. Evaluation of minimum clinically meaningful changes in scores on the National Eye Institute Visual Function Questionnaire (NEI-VFQ) SST Report Number 19. Ophthalmic Epidemiol. 2007;14(4):205–15.
doi: 10.1080/09286580701502970
Suñer IJ, Kokame GT, Yu E, Ward J, Dolan C, Bressler NM. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci. 2009;50(8):3629–35.
doi: 10.1167/iovs.08-3225
pubmed: 19255158
Korobelnik J, Daien V, Faure C, Tadayoni R, Giocanti-Aurégan A, Dot C, et al. Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study. Graefes Arch Clin Exp Ophthalmol. 2020;258(3):521–8.
doi: 10.1007/s00417-019-04592-9
pubmed: 31894377
Korobelnik JF, Daien V, Faure C, Tadayoni R, Giocanti-Aurégan A, Dot C, et al. Two-year outcomes of the APOLLON observational study of intravitreal aflibercept monotherapy in France in patients with diabetic macular edema. Sci Rep. 2022;12(1):18242.
doi: 10.1038/s41598-022-22838-1
pubmed: 36309572
pmcid: 9617874
Sivaprasad S, Ghanchi F, Kelly SP, Kotagiri A, Talks J, Scanlon P, et al. Evaluation of standard of care intravitreal aflibercept treatment of diabetic macular oedema treatment-naive patients in the UK: DRAKO study 12-month outcomes. Eye (Lond). 2022;36(1):64–71.
doi: 10.1038/s41433-021-01624-9
pubmed: 34244670
Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema: 2-year results from a comparative effectiveness randomized clinical trial. Ophthalmology. 2016;123(6):1351–9.
doi: 10.1016/j.ophtha.2016.02.022
pubmed: 26935357
Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, Ayala AR, Jampol LM, Aiello LP, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193–203.
Santhakumaran S, Salimi A, Brunetti VC, Galic J. Efficacy and safety of aflibercept therapy for diabetic macular edema: a systematic review and meta-analysis. J Curr Ophthalmol. 2022;34(2):133–47.
doi: 10.4103/joco.joco_308_21
pubmed: 36147265
pmcid: 9486998
Lovie-Kitchin JE. Is it time to confine Snellen charts to the annals of history? Ophthalmic Physiol Opt. 2015;35(6):631–6.
doi: 10.1111/opo.12252
pubmed: 26497296
Finger RP, Daien V, Talks JS, Mitchell P, Wong TY, Sakamoto T, et al. A novel tool to assess the quality of RWE to guide the management of retinal disease. Acta Ophthalmol. 2021;99(6):604–10.
doi: 10.1111/aos.14698
pubmed: 33369881
Finger RP, Sakamoto T, Talks J, Daien V, Wong T, Eldem B, et al. Navigating real-world evidence in ophthalmology: Modern Retina; 2021 [5 January 2021; cited May 2023]. Available from: https://www.modernretina.com/view/navigating-real-world-evidence-in-ophthalmology .