Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration

Abstract

Purpose: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France.

Methods: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here.

Results: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies.

Conclusion: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes.

Trial registration number: ClinicalTrials.gov Identifier: NCT02279537.

Keywords: Aflibercept; Intravitreal injections; Long-term treatment outcomes; Neovascular age-related macular degeneration; Real-world study.

Conflict of interest statement

SYC: consulting fees from Allergan, Bayer, Novartis, Roche, and Théa; CF: consulting fees from Allergan, Bayer, and Novartis; SB: consulting fees from Bayer, Allergan/AbbVie, Horus Pharma, Novartis, and Roche; HO: consulting fees from Allergan, Bayer, Novartis, Roche, and Théa; LK: consulting fees from Allergan/AbbVie, Alcon, Bayer, Krystal Biotech, Novartis, Regeneron, and Théa; MW: member of the French advisory board for Bayer. MD and FC declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1

Estimated rate of persistence with intravitreal aflibercept up to year 4

Fig. 2

Mean change from baseline in BCVA for the FAS (before switch) and 3 IVT-AFL treatment cohorts. *p < 0.05, **p < 0.01, and ***p < 0.001 versus baseline (signed-rank test). BCVA, best-corrected visual acuity; FAS, full analysis set; IVT-AFL, intravitreal aflibercept

Fig. 3

Mean change from baseline in CRT for the FAS (before switch) population and 3 IVT-AFL treatment cohorts. The mean change in CRT from baseline was significant for all time points and cohorts (p < 0.001; signed-rank test). CRT, central retinal thickness; FAS, full analysis set; IVT-AFL, intravitreal aflibercept