Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial

Abstract

Importance: To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD).

Objective: To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial.

Design, setting, and participants: The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments.

Interventions: Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase.

Main outcomes and measures: Mean change in BCVA and the number of injections from baseline to month 12.

Results: Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86).

Conclusions and relevance: Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified.

Trial registration: Clinicaltrials.Gov identifier: NCT02130024.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Gillies reports receiving honoraria and research support from and serving as an advisory board member for Novartis, Bayer, and Allergan. Dr Hunyor reports receiving honoraria from and serving as an advisory board members for Novartis and Bayer. Dr Arnold reports receiving honoraria from and serving as an advisory board member for Novartis, Bayer, and Allergen and receiving congress travel support from Novartis. Dr Guymer reports receiving honoraria from and serving as an advisory board member for Novartis, Bayer, and Roche/Genentech. Dr Wolf reports receiving Reading Centre fees from Novartis and Bayer and nonfinancial support from Heidelberg Engineering and Zeiss. Dr Pecheur reports receiving personal fees from Novartis and being a former employee of Novartis. Dr McAllister reports receiving honoraria from and serving as an advisory board member for Novartis and Bayer. No other disclosures are reported.

Figures

Figure.. Flow Diagram of Patient Disposition

The randomized population consisted of all randomized participants. The safety set consists of all participants who received at least 1 application of the study treatment and had at least 1 postbaseline safety assessment. The statement that a participant had no adverse events also constitutes a safety assessment. The full analysis set is composed of all participants who were randomized who had at least 1 postbaseline efficacy value for the primary end point. aOne participant was excluded from the safety set as the participant did not receive the study treatment.