Skip to main content
Top
Published in: Advances in Therapy 3/2017

Open Access 01-03-2017 | Review

The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in nAMD: Systematic Review and Network Meta-Analysis

Authors: Andriy Danyliv, Julie Glanville, Rachael McCool, Alberto Ferreira, Adrian Skelly, Ruth Pulikottil Jacob

Published in: Advances in Therapy | Issue 3/2017

Login to get access

Abstract

Introduction

Neovascular age-related macular degeneration (nAMD) is a chronic eye condition that causes severe deterioration of vision and ultimately blindness. Two vascular endothelial growth factor inhibitors are approved for nAMD treatment in Europe: ranibizumab and aflibercept. The European license for ranibizumab was updated with an individualized “treat and extend” (T&E) regimen, which involves more proactive treatment based on changes in best corrected visual acuity (BCVA) and/or anatomical outcomes. The aim of this publication is to compare the efficacy of the ranibizumab T&E regimen with other approved dosing regimens for nAMD on the basis of outcomes identified from a systematic review and subsequent NMA.

Methods

Following a systematic search of publications, to identify relevant studies, a repeated-measures network meta-analysis (NMA) was performed to estimate the relative effectiveness of ranibizumab T&E versus approved dosing regimens of ranibizumab and aflibercept. The analysis focused on licensed treatment regimens for nAMD. We examined mean change from baseline in BCVA on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Results

The systematic literature review identified 22,949 records, of which 23 studies were included in the NMA. At 12 months, the ranibizumab T&E dosing regimen vs ranibizumab pro re nata (PRN) was associated with small differences in change in BCVA, between 1.86 letter gain at 12 months and 2.35 letter gain at 24 months. A similar difference was observed in the aflibercept dosing regimen versus ranibizumab T&E ; 1.94 letter gain at 12 months and 3.31 letter gain at 24 months. All doses of ranibizumab and aflibercept showed similar effectiveness, and the differences between treatment options were not significant.

Conclusion

This study used novel repeated-measures NMA to synthesize efficacy results when treatment effects were reported at multiple follow-up times. This repeated-measures NMA suggests that treating patients with the ranibizumab T&E regimen yields similar effectiveness compared to other approved ranibizumab and aflibercept dosing regimens for nAMD treatment.
Funding: Novartis Pharmaceuticals UK Ltd, Surrey, UK.
Appendix
Available only for authorised users
Literature
1.
go back to reference Congdon N, O’Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477–85.CrossRefPubMed Congdon N, O’Colmain B, Klaver CC, et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004;122(4):477–85.CrossRefPubMed
2.
go back to reference Pascolini D, Mariotti SP, Pokharel GP, et al. 2002 Global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic Epidemiol. 2004;11(2):67–115.CrossRefPubMed Pascolini D, Mariotti SP, Pokharel GP, et al. 2002 Global update of available data on visual impairment: a compilation of population-based prevalence studies. Ophthalmic Epidemiol. 2004;11(2):67–115.CrossRefPubMed
3.
go back to reference Wong WL, 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;2(2):e106–16.CrossRefPubMed Wong WL, 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;2(2):e106–16.CrossRefPubMed
4.
go back to reference Bunce C, Xing W, Wormald R. Causes of blind and partial sight certifications in England and Wales: April 2007–March 2008. Eye. 2010;24(11):1692–9.CrossRefPubMed Bunce C, Xing W, Wormald R. Causes of blind and partial sight certifications in England and Wales: April 2007–March 2008. Eye. 2010;24(11):1692–9.CrossRefPubMed
5.
go back to reference Menon G, Walters G. New paradigms in the treatment of wet AMD: the impact of anti-VEGF therapy. Eye. 2009;23(Suppl 1):S1–7.CrossRefPubMed Menon G, Walters G. New paradigms in the treatment of wet AMD: the impact of anti-VEGF therapy. Eye. 2009;23(Suppl 1):S1–7.CrossRefPubMed
6.
go back to reference Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol. 2012;96(5):752–6.CrossRefPubMedPubMedCentral Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol. 2012;96(5):752–6.CrossRefPubMedPubMedCentral
7.
go back to reference Wong TY, Liew G, Mitchell P. Clinical update: new treatments for age-related macular degeneration. Lancet. 2007;370(9583):204–6.CrossRefPubMed Wong TY, Liew G, Mitchell P. Clinical update: new treatments for age-related macular degeneration. Lancet. 2007;370(9583):204–6.CrossRefPubMed
8.
go back to reference Bressler NM, Doan QV, Varma R, et al. Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration. Arch Ophthalmol. 2011;129(6):709–17.CrossRefPubMed Bressler NM, Doan QV, Varma R, et al. Estimated cases of legal blindness and visual impairment avoided using ranibizumab for choroidal neovascularization: non-Hispanic white population in the United States with age-related macular degeneration. Arch Ophthalmol. 2011;129(6):709–17.CrossRefPubMed
9.
go back to reference Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012;379(9827):1728–38.CrossRefPubMed Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012;379(9827):1728–38.CrossRefPubMed
12.
go back to reference 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;123(1):51–9.CrossRefPubMed 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;123(1):51–9.CrossRefPubMed
13.
go back to reference Berg K, Pedersen TR, 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.CrossRefPubMed Berg K, Pedersen TR, 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.CrossRefPubMed
14.
go back to reference Wykoff CC, Croft DE, Brown DM, 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.CrossRefPubMed Wykoff CC, Croft DE, Brown DM, 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.CrossRefPubMed
15.
go back to reference Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331(7521):897–900.CrossRefPubMedPubMedCentral Caldwell DM, Ades AE, Higgins JP. Simultaneous comparison of multiple treatments: combining direct and indirect evidence. BMJ. 2005;331(7521):897–900.CrossRefPubMedPubMedCentral
16.
go back to reference Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14(4):417–28.CrossRefPubMed Jansen JP, Fleurence R, Devine B, et al. Interpreting indirect treatment comparisons and network meta-analysis for health-care decision making: report of the ISPOR task force on indirect treatment comparisons good research practices: part 1. Value Health. 2011;14(4):417–28.CrossRefPubMed
17.
go back to reference Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–24.CrossRefPubMed Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–24.CrossRefPubMed
18.
go back to reference Hykin P, Chakravarthy U, Lotery A, McKibbin M, Napier J, Sivaprasad S. A retrospective study of the real-life utilization and effectiveness of ranibizumab therapy for neovascular age-related macular degeneration in the UK. Clin Ophthalmol. 2016;10:87–96.PubMedPubMedCentral Hykin P, Chakravarthy U, Lotery A, McKibbin M, Napier J, Sivaprasad S. A retrospective study of the real-life utilization and effectiveness of ranibizumab therapy for neovascular age-related macular degeneration in the UK. Clin Ophthalmol. 2016;10:87–96.PubMedPubMedCentral
19.
go back to reference Hodgson R, Barata T, Fleetwood K, Edwards M, Glanville J. Indirect treatment comparison of lucentis for wet age related macular degeneration. York Health Economics Consortium, York. 2014 Hodgson R, Barata T, Fleetwood K, Edwards M, Glanville J. Indirect treatment comparison of lucentis for wet age related macular degeneration. York Health Economics Consortium, York. 2014
20.
go back to reference Fitzgerald A, Cikalo M, Sreekanta A, et al. Systematic review of the clinical effectiveness and safety of lucentis for wet age-related macular degeneration. York: York Health Economics Consortium; 2014 Fitzgerald A, Cikalo M, Sreekanta A, et al. Systematic review of the clinical effectiveness and safety of lucentis for wet age-related macular degeneration. York: York Health Economics Consortium; 2014
21.
go back to reference National Insititute for Health and Care Excellence. Final guidance on the use of ranibizumab and pegaptanib for the treatment of age-related macular degeneration (AMD). London: National Insititute for Health and Care Excellence; 2008 (press release). National Insititute for Health and Care Excellence. Final guidance on the use of ranibizumab and pegaptanib for the treatment of age-related macular degeneration (AMD). London: National Insititute for Health and Care Excellence; 2008 (press release).
22.
go back to reference Australian Pharmaceutical Benefits Advisory Committee Indirect Comparisons Working Group. Report of the Indirect Comparisons Working Group to the Pharmaceutical Benefits Advisory Committee: Assessing Indirect Comparisons. Canberra: Australian Department of Health and Ageing, Pharmaceutical Benefits Advisory Committee, 2009. Australian Pharmaceutical Benefits Advisory Committee Indirect Comparisons Working Group. Report of the Indirect Comparisons Working Group to the Pharmaceutical Benefits Advisory Committee: Assessing Indirect Comparisons. Canberra: Australian Department of Health and Ageing, Pharmaceutical Benefits Advisory Committee, 2009.
23.
go back to reference Dakin HA, Welton NJ, Ades AE, Collins S, Orme M, Kelly S. Mixed treatment comparison of repeated measurements of a continuous endpoint: an example using topical treatments for primary open-angle glaucoma and ocular hypertension. Stat Med. 2011;30(20):2511–35.CrossRefPubMed Dakin HA, Welton NJ, Ades AE, Collins S, Orme M, Kelly S. Mixed treatment comparison of repeated measurements of a continuous endpoint: an example using topical treatments for primary open-angle glaucoma and ocular hypertension. Stat Med. 2011;30(20):2511–35.CrossRefPubMed
24.
go back to reference Ding Y, Fu H. Bayesian indirect and mixed treatment comparisons across longitudinal time points. Stat Med. 2013;32(15):2613–28.CrossRefPubMed Ding Y, Fu H. Bayesian indirect and mixed treatment comparisons across longitudinal time points. Stat Med. 2013;32(15):2613–28.CrossRefPubMed
25.
go back to reference London NJ, Fung AE, Dugel PU, et al. A Prospective evaluation of ranibizumab for retinal pigment epithelial detachments in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50(5):2379. London NJ, Fung AE, Dugel PU, et al. A Prospective evaluation of ranibizumab for retinal pigment epithelial detachments in neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2009;50(5):2379.
26.
go back to reference Moon E, et al. Monthly versus PRN ranibizumab for neovascular AMD: a randomized phase 2 open-label study. Invest Ophthalmol Vis Sci 2011;52(6):133. Moon E, et al. Monthly versus PRN ranibizumab for neovascular AMD: a randomized phase 2 open-label study. Invest Ophthalmol Vis Sci 2011;52(6):133.
27.
go back to reference Cameron C, Fireman B, Hutton B, et al. Network meta-analysis incorporating randomized controlled trials and non-randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities. Syst Rev. 2015;4:147.CrossRefPubMedPubMedCentral Cameron C, Fireman B, Hutton B, et al. Network meta-analysis incorporating randomized controlled trials and non-randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities. Syst Rev. 2015;4:147.CrossRefPubMedPubMedCentral
28.
go back to reference Busbee BG, Ho AC, Brown DM, et al. 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(5):1046–56.CrossRefPubMed Busbee BG, Ho AC, Brown DM, et al. 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(5):1046–56.CrossRefPubMed
Metadata
Title
The Clinical Effectiveness of Ranibizumab Treat and Extend Regimen in nAMD: Systematic Review and Network Meta-Analysis
Authors
Andriy Danyliv
Julie Glanville
Rachael McCool
Alberto Ferreira
Adrian Skelly
Ruth Pulikottil Jacob
Publication date
01-03-2017
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 3/2017
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-017-0484-0

Other articles of this Issue 3/2017

Advances in Therapy 3/2017 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.