Real world evidence of use of anti-VEGF therapy in Denmark

Abstract

Objective: This study evaluates real-world evidence regarding the frequency of anti-vascular-endothelial-growth-factor (VEGF) injections during the first year of therapy of treatment-naïve patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) from the Danish National Patient Registry. There was a switch in anti-VEGF treatment for naïve nAMD patients during the study period, following the introduction of aflibercept, which was expected to reduce the injection frequency relative to ranibizumab due to a perception of prolonged treatment duration of aflibercept.

Methods: All treatment-naïve nAMD, DME or RVO patients who received an intravitreal injection in Denmark from 1 January 2012 to 31 July 2015 were eligible for inclusion. Patients were required to have been treated for at least one year and, for nAMD, to have received at least three injections during the first four months of treatment. Patients were allocated to half-year groupings (2012/1 to 2014/1) based on registration of their first intravitreal injection. Injection frequency during the first year of treatment was calculated for each group and t-tests investigated whether injection frequencies changed over time.

Results: In treatment naïve nAMD patients (n = 500), the mean (SD) number of anti-VEGF injections increased significantly from 6.04 (1.71) in 2012/1 to 6.73 (1.62) in 2014/1 (p = .001; 2012/1 and 2012/2 vs. 2014/1) across all treatments. A similar trend was found for DME patients (n = 76) from 2012/1 to 2014/1 and RVO patients (n = 82) from 2012/2 to 2014/1, with mean injection frequencies increasing significantly from 5.14 (2.29) to 5.93 (1.98) (p = .007), and from 4.83 (1.21) to 6.08 (1.55) (p = .024), respectively. Post hoc sensitivity analysis also found a significant increase in injection frequency in nAMD patients who did not receive a loading phase (4.55 in 2012/1 and 5.05 in 2014/1; p = .006; n = 616).

Conclusions: In contrast to the decrease in injection frequency predicted with a switch to aflibercept treatment for nAMD, our study showed that injection frequencies increased significantly from 2012 to 2014 in patients initiating therapy across the three diseases.

Keywords:

• Aflibercept
• Macular edema
• Observational study
• Ranibizumab
• Registries
• Retinal vein occlusion
• Wet macular degeneration

Notes

Transparency

Declaration of funding

This study was funded by Novartis Healthcare.

Declaration of financial/other relationships

H.V. has disclosed that he has acted as a consultant to Alcon Nordic, Bayer, Novartis Healthcare, and Allergan. T.K.O. and J.Z. have disclosed that they are employees of DLi Market Intelligence, a company that received funding from Novartis to help conduct this study. M.S.H. has disclosed that he is an employee of Novartis Healthcare.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work. Peer reviewer 1 has disclosed that he has received grants from Allergan and Regeneron, and is a consultant to Allergan, Regeneron, Boehringer Ingelheim and Momenta. Peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

The authors were assisted in the preparation of the manuscript by Karen Stanford, Novartis Ireland Limited, Dublin, Ireland. Writing support was funded by the study sponsor. The authors thank Mikkel Misfeldt for valuable comments on the study design while he was an employee of the study sponsor.

Notes

1 Lucentis is a registered trade name of Genentech/Novartis

2 Eylea is a registered trade name of Regeneron Pharmaceuticals/Bayer

3 Avastin is a registered trade name of Genentech/Roche