A single-arm, investigator-initiated study of the efficacy, safety, and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration previously treated with ranibizumab or bevacizumab (ASSESS study): 12-month analysis

Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser, Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser

Abstract

Summary statement: In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline.

Purpose: Switching therapies in neovascular age-related macular degeneration (AMD) may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI) in subjects previously treated with ranibizumab and/or bevacizumab.

Methods: Subjects (n=26) were given monthly 2 mg of IAI for 3 months, followed by 2 mg once in every 2 months for up to 12 months. The mean absolute change from baseline in central subfield thickness (CST) measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA) early treatment in diabetic retinopathy study (ETDRS) letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated.

Results: There was a mean decrease in CST of -50.3 μm (P<0.001) and a mean increase in ETDRS BCVA of +9.2 letters (P<0.001). Twenty-seven percent of subjects experienced a ≥15-letter improvement in visual acuity, and no subject lost ≥3 lines of vision from baseline. Fifty percent of subjects were 20/40 or better, and 11.5% of subjects were 20/200 or worse at month 12.

Conclusion: Fixed IAI dosing regimen for 12 months demonstrated improved anatomic and vision endpoints in subjects with active exudative AMD.

Keywords: aflibercept; age-related macular degeneration; bevacizumab; ranibizumab; vascular endothelial growth factors.

Figures

Figure 1
Figure 1
ASSESS study design. Abbreviations: ETDRS, early treatment in diabetic retinopathy study; IAI, intravitreal aflibercept injection.
Figure 2
Figure 2
Mean change from baseline in central subfield thickness. Note: *Indicates that the value is statistically significant.
Figure 3
Figure 3
Mean change from baseline in BCVA score. Note: *Indicates that the value is statistically significant. Abbreviation: BCVA, best-corrected visual acuity.
Figure 4
Figure 4
Change from baseline in ETDRS score at 12 month study endpoint. Abbreviation: ETDRS, early treatment in diabetic retinopathy study.
Figure 5
Figure 5
OCT fluid status in patients at month 12. Abbreviation: OCT, optical coherence tomography.
Figure 6
Figure 6
Representative patient from the ASSESS trial demonstrating treatment response. Abbreviation: BCVA, best-corrected visual acuity.

References

    1. Rosenfeld PJ, Brown DM, Heier JS, et al. MARINA Study Group Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419–1431.
    1. ANCHOR Study Group Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009;116(1):57–65.
    1. Busbee BG, Ho AC, Brown DM, et al. HARBOR Study Group Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2013;120:1046–1056.
    1. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20:4368–4380.
    1. 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;15:171–185.
    1. Rakic JM, Lambert V, Devy L, et al. Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization. Invest Ophthalmol Vis Sci. 2003;44:3186–3193.
    1. Stewart MW. What are the half-lives of ranibizumab and aflibercept (VEGF Trap-eye) in human eyes? Calculations with a mathematical model. Eye Rep. 2011;1.1:e5.
    1. CATT Research Group. Martin DF, Maguire MG, et al. Ranibizumab and Bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897–1908.
    1. Martin DF, Maguire MG, Fine SL, et al. Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) Research Group Ranibizumab and bevacizumab for neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119:1388–1398.
    1. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K, SEVEN-UP Study Group Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multi-center cohort study (SEVEN-UP) Ophthalmology. 2013;120:1–8.
    1. Silva R, Axer-Siegel R, Eldem B, et al. SECURE Study Group The SECURE study: long-term safety of ranibizumab 0.5 mg in neovascular age-related macular degeneration. Ophthalmology. 2013;120:130–139.
    1. 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;119:1175–1183.
    1. Singh RP, Srivastava S, Ehlers JP, Bedi R, Schachat AP, Kaiser PK. A single-arm, investigator-initiated study of the efficacy, safety and tolerability of intravitreal aflibercept injection in subjects with exudative age-related macular degeneration, previously treated with ranibizumab or bevacizumab: 6-month interim analysis. Br J Ophthalmol. 2014;98(suppl 1):i22–i27.
    1. Eylea [package insert] Tarrytown, NY: Regeneron Pharmaceuticals, Inc; 2011. Available from: .
    1. Beck RW, Moke PS, Turpin AH, et al. A computerized method of visual acuity testing: adaptation of the early treatment of diabetic retinopathy study testing protocol. Am J Ophthalmol. 2003;135(2):194–205.
    1. Cho H, Shah CP, Weber M, Heier JS. Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab. Br J Ophthalmol. 2013;0:1–4.
    1. Bakall B, Folk JC, Boldt HC, et al. Aflibercept therapy for exudative age-related macular degeneration. Am J Ophthalmol. 2013;156:15–22.
    1. Ho VY, Yeh S, Olsen TW, et al. Short-term outcomes of aflibercept for neovascular age-related macular degeneration in eyes previously treated with other vascular endothelial growth factor inhibitors. Am J Ophthalmol. 2013;156:23–28.
    1. Yonekawa Y, Andreoli C, Miller JB, et al. Conversion to aflibercept for chronic refractory or recurrent neovascular age-related macular degeneration. Am J Ophthalmol. 2013;156:29–35.
    1. Stewart MW, Rosenfeld PJ. Predicted biological activity of intravitreal VEGF Trap. Br J Ophthalmol. 2008;92(5):667–668.
    1. Heier JS, Brown DM, Chong V, et al. VIEW 1 and VIEW 2 Study Groups Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537–2548.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir