EXTEND III: Efficacy and safety of ranibizumab in South Korean and Taiwanese patients with subfoveal CNV secondary to AMD

  • Oh-Woong Kwon
  • Fenq Lih Lee
  • Hum Chung
  • Chi-Chun Lai
  • Shwu-Jiuan Sheu
  • Young-Hee Yoon
  • on behalf of the EXTEND III study group
Medical Ophthalmology

Abstract

Background

The purpose of this study was to investigate the efficacy and safety of intravitreal ranibizumab 0.5 mg in South Korean and Taiwanese patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD).

Methods

This was a 12-month, open-label, single-arm, multi-center, phase III study. Ninety-five patients (Taiwanese: 51; South Korean: 44) were included in the study. Key outcome measures assessed included: mean change in best-corrected visual acuity (BCVA) from baseline to months 4 (primary endpoint) and 12 (secondary endpoint); other secondary endpoints comprising categorized mean change in BCVA from baseline at month 4 and month 12, mean change in BCVA from baseline at month 4 and month 12 per baseline characteristics; and incidence of ocular and non-ocular adverse events and serious adverse events (SAEs) at month 12.

Results

The mean BCVA change improved significantly (p < 0.0001) from baseline to both month 4 (+9.3 letters) and month 12 (+10.1 letters). At month 12, the proportion of patients who gained ≥5, 10, or 15 letters from baseline was 75.8%, 54.7%, and 32.6% respectively. Total and CNV lesion area significantly decreased from baseline (p < 0.0001). About 57% of patients showed complete absence of fluorescein leakage at month 12. Mean change from baseline visual acuity scores also increased significantly over time for all subgroups. At month 12, ocular SAEs occurred in 2.1% of patients (out of which one patient [1.1%] experienced endophthalmitis) and 16.8% of patients experienced non-ocular SAEs. There were no deaths reported during the study.

Conclusions

Consistent with previous studies in Caucasian and Japanese populations, EXTEND III confirms that monthly intravitreal injections of ranibizumab 0.5 mg administered over 12 months is effective and well-tolerated in South Korean and Taiwanese patients with subfoveal CNV secondary to AMD.

Keywords

Choroidal neovascularization Age-related macular degeneration Best-corrected visual acuity Intravitreal ranibizumab Fluorescein leakage 

References

  1. 1.
    WHO. Magnitude and causes of visual impairment [fact sheet no. 282]. Geneva: World Health Organization. URL http://www.who.int/mediacentre/factsheets/fs282/en/. Accessed on August 01, 2011
  2. 2.
    Bhisitkul RB (2006) Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol 90:1542–1547PubMedCrossRefGoogle Scholar
  3. 3.
    Krzystolik MG, Afshari MA, Adamis AP, Gaudreault J, Gragoudas ES, Michaud NA, Li W, Connolly E, O'Neill CA, Miller JW (2002) Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment. Arch Ophthalmol 120:338–346PubMedCrossRefGoogle Scholar
  4. 4.
    Witmer AN, Vrensen GF, Van Noorden CJ, Schlingemann RO (2003) Vascular endothelial growth factors and angiogenesis in eye disease. Prog Retin Eye Res 22:1–29PubMedCrossRefGoogle Scholar
  5. 5.
    Ferrara N, Damico L, Shams N, Lowman H, Kim R (2006) Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 26:859–870PubMedCrossRefGoogle Scholar
  6. 6.
    Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M (2007) Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res 85:425–430PubMedCrossRefGoogle Scholar
  7. 7.
    Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S, ANCHOR Study Group (2006) Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 355:1432–1444PubMedCrossRefGoogle Scholar
  8. 8.
    Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, MARINA Study Group (2006) Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 355:1419–1431PubMedCrossRefGoogle Scholar
  9. 9.
    Brown DM, Michels M, Kaiser PK, Heier JS, Sy JP, Ianchulev T (2009) Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology 116:57–65, e5PubMedCrossRefGoogle Scholar
  10. 10.
    Tano Y, Ohji M (2010) EXTEND-I: safety and efficacy of ranibizumab in Japanese patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. Acta Ophthalmol 88:309–316PubMedCrossRefGoogle Scholar
  11. 11.
    Hsu WM, Cheng CY, Liu JH, Tsai SY, Chou P (2004) Prevalence and causes of visual impairment in an elderly Chinese population in Taiwan: the Shihpai Eye Study. Ophthalmology 111:62–69PubMedCrossRefGoogle Scholar
  12. 12.
    Liu JH, Cheng CY, Chen SJ, Lee FL (2001) Visual impairment in a Taiwanese population: prevalence, causes, and socioeconomic factors. Ophthalmic Epidemiol 8:339–350PubMedGoogle Scholar
  13. 13.
    Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, Oshima Y, Ishibashi T, Nose Y (2003) Risk factors for age related maculopathy in a Japanese population: the Hisayama Study. Br J Ophthalmol 87:469–472PubMedCrossRefGoogle Scholar
  14. 14.
    Wong TY, Loon SC, Saw SM (2006) The epidemiology of age related eye diseases in Asia. Br J Ophthalmol 90:506–511PubMedCrossRefGoogle Scholar
  15. 15.
    Lee FL, Kwon OW, Chung H, Lai CC, Sheu SJ, Yoon YH, EXTEND III Study Group (2012) Ranibizumab in South Korean and Taiwanese patients with age-related macular degeneration: primary outcome of the EXTEND III study. Acta Ophthalmol [Epub ahead of print]. doi:10.1111/j.1755-3768.2011.02262.x
  16. 16.
    Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR (2007) Ranibizumab for predominantly classic neovascular age-related macular degeneration: subgroup analysis of first-year ANCHOR results. Am J Ophthalmol 144:850–857PubMedCrossRefGoogle Scholar
  17. 17.
    Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, Ma C, Menchini U, Miller J, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Strong HA, Stur M, Su XY, Virgili G; Treatment of Age-related Macular Degeneration with Photodynamic Therapy study group; Verteporfin in Photodynamic Therapy study group (2003) Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol 136:407–418PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Oh-Woong Kwon
    • 1
  • Fenq Lih Lee
    • 2
  • Hum Chung
    • 3
  • Chi-Chun Lai
    • 4
  • Shwu-Jiuan Sheu
    • 5
  • Young-Hee Yoon
    • 6
  • on behalf of the EXTEND III study group
  1. 1.The Retina CenterNune Eye HospitalSeoulKorea
  2. 2.Taipei Veterans General Hospital No. 201TaipeiTaiwan
  3. 3.Department of OphthalmologySeoul National University HospitalSeoulKorea
  4. 4.Chang-Gung Memorial HospitalLin-KoTaiwan
  5. 5.Kaohsiung Veterans General Hospital, KaohsiungNational Yang-Ming UniversityTaipeiTaiwan
  6. 6.Department of Ophthalmology, Asan Medical Center, College of MedicineUniversity of UlsanSeoulKorea

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