Background/aims To evaluate the efficacy and safety of individualised 2.0 mg intravitreal aflibercept retreatment for diabetic macular oedema (DME) through the fifth year of management.
Methods This is a phase IV, 2-year, open-label extension study. Sixty patients completing the 3-year VISTA DME (Study of Intravitreal Aflibercept Injection in Patients With Diabetic Macular Edema) phase III trial enrolled in the ENDURANCE (Long-Term Efficacy and Safety of Intravitreal Aflibercept for the Treatment of DME in Subjects Who Completed the VISTA DME Trial) extension study. All patients received aflibercept in the presence of clinically relevant DME. Intervals between visits were prescribed according to disease activity. The main outcome measure was mean aflibercept injections given through 2 years.
Results A mean of 7.7 aflibercept injections were administered through 2 years. Fifteen (25%) patients required no retreatment and 48% (n=29) of patients received five or fewer injections through 2 years. Among patients who received at least one aflibercept retreatment during ENDURANCE, the mean number of injections through 2 years was 9.5. The mean visual acuity and central retinal thickness gains achieved during VISTA DME were maintained and stable during ENDURANCE. The most notable safety signal was progression of diabetic retinopathy. Six (10%) patients converted from non-proliferative to proliferative diabetic retinopathy (PDR), and a total of eight patients experienced PDR events occurring at a mean of 387 days following the previous aflibercept treatment.
Conclusion The need for aflibercept retreatment was substantially reduced in the fourth and fifth years of aflibercept dosing for DME following initiation of therapy in the VISTA DME trial. While vision gains achieved during the 3-year VISTA DME trial were maintained through ENDURANCE with a reduced treatment burden, clinically relevant worsening of diabetic retinopathy was observed with progression to PDR in 10% of the eyes.
Trial registration number NCT02299336
- treatment medical
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Contributors Research design: CCW. Data acquisition and/or research execution: CCW, WCO, RNK, DMB, WLC, DSB. Data analysis and/or interpretation: CCW, WCO. Manuscript preparation: CCW, WCO, RNK, DMB, WLC, DSB.
Funding Research grant from Regeneron, Tarrytown, NY. The funding organization had no role in the design or conduct of this research.
Competing interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare financial support for the submitted work from Regeneron, Tarrytown, New York. CCW reports grants and personal fees from Alcon, grants from Allegro, grants and personal fees from Allergan, grants from Apellis, grants from Aura, grants and personal fees from Clearside, grants and personal fees from Genentech, grants and personal fees from Iconic Therapeutics, grants from NEI, grants from NIH, grants from Novartis, grants from Ohr Pharmaceuticals, grants from Ophthotech, grants from pSivida, grants and personal fees from Regeneron, grants from Roche, grants from Santen, grants from SciFluor, grants from Tyrogenex, personal fees from Alimera Sciences, personal fees from Alnylam Pharmaceuticals, personal fees from Bayer, personal fees from DORC, personal fees from ONL Therapeutics, personal fees from ThromboGenics and personal fees from Valeant. RNK reports grants and personal fees from Allergan, personal fees from Genentech, grants and personal fees from Regeneron, grants and personal fees from Santen and grants from Clearside Biomedical. DMB reports grants and personal fees from Regeneron, personal fees from Bayer, personal fees from Adverum, grants and personal fees from Allergan, grants and personal fees from Regenxbio, grants from Clearside Biomedical, grants and personal fees from Ohr, personal fees from Bayer, personal fees from Heidelberg, grants and personal fees from Novartis, personal fees from Optos, personal fees from Zeiss, grants and personal fees from ThromboGenics, grants from Ophthotech and grants from NEI. WLC reports grants and personal fees from Genentech/Roche, grants and personal fees from Ohr Pharmaceuticals, grants from Allergan, grants from Aerpio, and grants, personal fees and non-financial support from Regeneron Pharmaceuticals. DSB reports personal fees from Allergan, personal fees from Alcon, personal fees from Novartis, personal fees from Genentech, personal fees from Roche, personal fees from Bayer, personal fees from Regeneron, personal fees and other from Allegro. No other relationships or activities that could appear to have influenced the submitted work.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval Sterling Institutional Review Board, Atlanta, GA.
Provenance and peer review Not commissioned; externally peer reviewed.
Collaborators Members of the ENDURANCE Study Group: CCW, WCO, RNK, DMB, WLC, DSB, Alok S. Bansal, Matthew S. Benz, Edwin E. Boldrey, J. Luigi Borrillo, Louis K. Chang, Eric Chen, Thomas G. Chu, Pouya N. Dayani, Daniel Esmaili, Richard H. Fish, Christopher R. Henry, David L. Johnson, Rosa Y. Kim, Ryan T. Le, David Liao, James C. Major Jr, Roger L. Novack, Ronan E. O’Malley, James D. Palmer, John F. Payne, Firas M. Rahhal, Richard H. Roe, Amy C. Schefler, Ankoor R. Shah, Homayoun Tabandeh, Rui Wang, John A. Wells III, Mark R. Wieland, Tien P. Wong.