Skip to main content
SpringerLink
Log in

The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK

  • Original Research
  • Published:
Advances in Therapy Aims and scope Submit manuscript

Abstract

Introduction

Wet age-related macular degeneration (AMD) is a chronic eye condition that causes severe deterioration of vision and even blindness. Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept. Patients with wet AMD require frequent and long-term monitoring for treatment to be effective, contributing to a substantial resource burden at wet AMD centers. The European license for ranibizumab was recently updated with an individualized ‘treat and extend’ (T&E) regimen, comprising a structured monitoring and treatment protocol. This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting.

Methods

An individual patient-level simulation model was developed utilizing treatment effects from a network meta-analysis of randomized controlled trials. The model was conducted from a UK National Health Service (NHS) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model. Additional scenario analyses were conducted to assess the impact of changes to the model inputs.

Results

Ranibizumab T&E was found to be more effective and less costly than aflibercept, providing, on average, an additional 1.058 quality-adjusted life years (QALYs) and a cost-saving of £19,604 over a lifetime horizon. At list price, ranibizumab T&E was found to be cost-effective versus aflibercept in 100% of simulations at a willingness-to-pay threshold of £20,000 per QALY. The robustness of the results was tested in several scenario analyses; ranibizumab T&E was found to be more effective, and less costly, than aflibercept in the vast majority of cases.

Conclusion

This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS resources than aflibercept, and could, therefore, be considered as a first-line regimen for patients with wet AMD in the UK.

Funding

Novartis Pharmaceuticals UK Limited.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Freund KB, Korobelnik JF, Devenyi R, Framme C, Galic J, Herbert E, et al. Treat-and-extend regimens with anti-VEGF agents in retinal diseases: a literature review and consensus recommendations. Retina (Philadelphia, Pa). 2015;35(8):1489–506.

    Article  CAS  Google Scholar 

  2. Bunce C, Xing W, Wormald R. Causes of blind and partial sight certifications in England and Wales: April 2007–March 2008. Eye (London, England). 2010;24(11):1692–9.

    Article  CAS  Google Scholar 

  3. 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.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  5. European Medicines Agency (EMA). Lucentis 10 mg/ml solution for injection. Summary of Product Characteristics. 2009. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000715/WC500043546.pdf. Accessed 11 Feb 2016.

  6. European Medicines Agency (EMA). Eylea 40 mg/ml solution for injection in pre-filled syringe. Summary of product characteristics. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002392/WC500135815.pdf. Accessed Feb 2016.

  7. The Royal College of Ophthalmologists. Increasing demand on hospital eye services risks patients losing vision. 2016. https://www.rcophth.ac.uk/2016/03/increasing-demand-on-hospital-eye-services-risks-patients-losing-vision/. Accessed 18 Mar 2016.

  8. Amoaku W, Blakeney S, Freeman M, Gale R, Johnston R, Kelly SP, et al. Action on AMD. Optimising patient management: act now to ensure current and continual delivery of best possible patient care. Eye. 2012;26(Suppl 1):S2–21.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tufail AXW, Johnston R, Akerele T, McKibbin M, Downey L, Natha S, Chakravarthy U, Bailey C, Khan R, Antcliff R, Armstrong S, Varma A, Kumar V, Tsaloumas M, Mandal K, Bunce C. The neovascular age-related macular degeneration database: multicenter study of 92 976 ranibizumab injections: report 1: visual acuity. Ophthalmology. 2014;121(5):1092–101.

    Article  Google Scholar 

  10. Oubraham H, Cohen SY, Samimi S, Marotte D, Bouzaher I, Bonicel P, et al. Inject and extend dosing versus dosing as needed: a comparative retrospective study of ranibizumab in exudative age-related macular degeneration. Retina (Philadelphia, Pa). 2011;31(1):26–30.

    Article  CAS  Google Scholar 

  11. Abraham P, Yue H, Wilson L. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER study year 2. Am J Ophthalmol. 2010;150(3):315–24.e1.

  12. Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, et al. Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008;145(2):239–48.

    Article  CAS  PubMed  Google Scholar 

  13. Schmidt-Erfurth U, Eldem B, Guymer R, Korobelnik JF, Schlingemann RO, Axer-Siegel R, et al. Efficacy and safety of monthly versus quarterly ranibizumab treatment in neovascular age-related macular degeneration: the EXCITE study. Ophthalmology. 2011;118(5):831–9.

    Article  PubMed  Google Scholar 

  14. Berg K, Hadzalic E, Gjertsen I, Forsaa V, Berger LH, Kinge B, 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.

    Article  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Wykoff CC, Croft DE, Brown DM, Wang R, Payne JF, Clark L, 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.

    Article  PubMed  Google Scholar 

  17. National Health Service North East Treatment Advisory Group. Aflibercept (Eylea®) for neovascular age-related macular degeneration. 2012. http://www.netag.nhs.uk/files/appraisal-reports/Aflibercept%20for%20AMD%20-%20NETAG%20appraisal%20report%20-%20-Jan2013-%20-%20WEB%20VERSION.pdf. Accessed 18 Mar 2016.

  18. National Institute for Health and Care Excellence (NICE). Guide to the methods of technology appraisal 2013. 2013. https://www.nice.org.uk/article/PMG9/chapter/1-Introduction. Accessed Feb 2016.

  19. National Institute for Health and Care Excellence (NICE). NICE Technology Appraisal Guidance [TA294]. Aflibercept solution for injection for treating wet age related macular degeneration. https://www.nice.org.uk/guidance/ta294. Accessed Feb 2016.

  20. National Institute for Health and Care Excellence (NICE). NICE Technology Appraisal Guidance [TA155]. Ranibizumab and pegaptanib for the treatment of age-related macular degeneration. 2008. http://www.nice.org.uk/guidance/TA155. Accessed 13 Oct 2015.

  21. Ding Y, Fu H. Bayesian indirect and mixed treatment comparisons across longitudinal time points. Stat Med. 2013;32(15):2613–28.

    Article  PubMed  Google Scholar 

  22. Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. Lancet (London, England). 2013;382(9900):1258–67.

    Article  CAS  Google Scholar 

  23. Elliott DB, Yang KC, Whitaker D. Visual acuity changes throughout adulthood in normal, healthy eyes: seeing beyond 6/6. Optom Vis Sci Offi Publ Am Acad Optom. 1995;72(3):186–91.

    Article  CAS  Google Scholar 

  24. Frisen L, Frisen M. How good is normal visual acuity? A study of letter acuity thresholds as a function of age. Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Albrecht von Graefe’s Archive Clin Exp Ophthalmol. 1981;215(3):149–57.

    Article  CAS  Google Scholar 

  25. Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, et al. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology. 2008;115(1):116–26.

    Article  PubMed  Google Scholar 

  26. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537–48.

    Article  PubMed  Google Scholar 

  27. National Institute for Health and Care Excellence (NICE). Aflibercept solution for injection for treating wet age related macular degeneration. 2013. Costing template. https://www.nice.org.uk/guidance/ta294/resources. Accessed Feb 2016.

  28. Czoski-Murray C, Carlton J, Brazier J, Young T, Papo NL, Kang HK. Valuing condition-specific health states using simulation contact lenses. Value Health J Int Soc Pharmacoecon Outcomes Res. 2009;12(5):793–9.

    Article  Google Scholar 

  29. National Life Tables, United Kingdom, 2012-2014: Office for National Statistics; September 2015. http://www.ons.gov.uk/ons/rel/lifetables/national-life-tables/2012-2014/index.html. Accessed Dec 2015.

  30. Christ SL, Lee DJ, Lam BL, Zheng DD, Arheart KL. Assessment of the effect of visual impairment on mortality through multiple health pathways: structural equation modeling. Invest Ophthalmol Vis Sci. 2008;49(8):3318–23.

    Article  PubMed  Google Scholar 

  31. Arnold JJ, Campain A, Barthelmes D, Simpson JM, Guymer RH, Hunyor AP, et al. Two-year outcomes of “treat and extend” intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology. 2015;122(6):1212–9.

    Article  PubMed  Google Scholar 

  32. Gupta OP, Shienbaum G, Patel AH, Fecarotta C, Kaiser RS, Regillo CD. A treat and extend regimen using ranibizumab for neovascular age-related macular degeneration clinical and economic impact. Ophthalmology. 2010;117(11):2134–40.

    Article  PubMed  Google Scholar 

  33. Spaide R. Ranibizumab according to need: a treatment for age-related macular degeneration. Am J Ophthalmol. 2007;143(4):679–80.

    Article  PubMed  Google Scholar 

  34. Stone TW. Preferences and trends (PAT) survey. Toronto: Am Soc Retina Spec (ASRS); 2013.

    Google Scholar 

  35. Rayess N, Houston SKS III, Gupta OP, Ho AC, Regillo CD. Three year treatment outcomes for neovascular age-related macular degeneration using a “treat and extend” regimen. Am J Ophthalmol. 2014;. doi:10.1016/j.ajo.2014.09.011.

    Google Scholar 

  36. Gillies MC, Campain A, Barthelmes D, Simpson JM, Arnold JJ, Guymer RH, et al. Long-term outcomes of treatment of neovascular age-related macular degeneration: data from an observational study. Ophthalmology. 2015;122(9):1837–45.

    Article  PubMed  Google Scholar 

  37. Regnier SA, Malcolm W, Haig J, Xue W. Cost-effectiveness of ranibizumab versus aflibercept in the treatment of visual impairment due to diabetic macular edema: a UK healthcare perspective. ClinicoEcon Outcomes Res CEOR. 2015;7:235–47.

    Article  Google Scholar 

  38. Dakin HA, et al. 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.

    Article  PubMed  Google Scholar 

  39. Monthly Index of Medical Specialities (MIMS). Available at: http://www.mims.co.uk/drugs/eye/diagnostic-and-surgical. Accessed Jun 2016.

  40. Department of Health. NHS Reference Costs 2014-2015. National schedule of reference costs: the main schedule. https://www.gov.uk/government/publications/nhs-reference-costs-2014-to-2015. Accessed 19 Jan 2016.

Download references

Acknowledgments

All costs associated with the development of this manuscript, and the article processing charges and open access fee for this publication were funded by Novartis Pharmaceuticals UK Limited. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. No further support was provided to the authors with regards to medical writing, editorial or other assistance.

Disclosures

Ruth Pulikottil-Jacob is an employee of Novartis Pharmaceuticals UK Limited. Wrik Ghosh, Rose Wickstead, and Jeanette Kusel are employees of Costello Medical Consulting Ltd., Lindsay Claxton and Matthew Taylor are employees of York Health Economics Consortium, and Kelly Fleetwood is an employee of Quantics, all of whom were contracted by Novartis Pharmaceuticals UK Limited to work on this study.

Compliance with Ethics Guidelines

This article is based on previously conducted studies and does not involve any new studies of human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

  1. Costello Medical Consulting Ltd., Cambridge, UK

    Wrik Ghosh, Rose Wickstead & Jeanette Kusel

  2. York Health Economics Consortium, University of York, York, UK

    Lindsay Claxton & Matthew Taylor

  3. Quantics, Edinburgh, UK

    Kelly Fleetwood

  4. Novartis Pharmaceuticals UK Limited, Surrey, UK

    Ruth Pulikottil-Jacob

Authors
  1. Wrik Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rose Wickstead
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lindsay Claxton
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jeanette Kusel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kelly Fleetwood
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ruth Pulikottil-Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ruth Pulikottil-Jacob.

Additional information

Enhanced content

To view enhanced content for this article go to http://www.medengine.com/Redeem/BBD4F06049B3BD03.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 536 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ghosh, W., Wickstead, R., Claxton, L. et al. The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK. Adv Ther 33, 1660–1676 (2016). https://doi.org/10.1007/s12325-016-0367-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12325-016-0367-9

Keywords

Search

Navigation