Elsevier

Ophthalmology

Volume 121, Issue 11, November 2014, Pages 2247-2254
Ophthalmology

Original article
Intravitreal Aflibercept for Diabetic Macular Edema

Presented at the American Academy of Ophthalmology Annual Meeting, November 2013. This was an annual meeting paper presentation.
https://doi.org/10.1016/j.ophtha.2014.05.006Get rights and content

Purpose

A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).

Design

Two similarly designed, double-masked, randomized, phase 3 trials, VISTADME and VIVIDDME.

Participants

We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.

Methods

Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.

Main Outcome Measures

The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.

Results

Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration–defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.

Conclusions

At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.

Section snippets

Methods

The VISTA and VIVID studies were 2 phase 3, randomized, double-masked, active-controlled, 148-week trials. The VISTA study (registered at www.clinicaltrials.gov; NCT01363440) was conducted across 54 sites in the United States and the VIVID study (registered at www.clinicaltrials.gov; NCT01331681) was conducted at 73 sites across Europe, Japan, and Australia (Appendix 1 provides a list of study investigators; available at www.aaojournal.org). Each clinical site's respective institutional review

Patient Disposition, Baseline Characteristics, and Treatment Experience

The VISTA study randomized 466 patients and VIVID, 406 patients, each with 1 study eye (Appendix 6; available at www.aaojournal.org). Overall, demographics and baseline characteristics of patients were similar across all treatment groups in both studies (Table 1). However, VISTA included a greater proportion of Black or African-American patients and VIVID had a greater proportion of Asian patients. In addition, more eyes in VISTA had prior anti-VEGF therapy for DME compared with VIVID (42.9% vs

Discussion

The VIVID and VISTA studies provide the first head-to-head comparisons of anti-VEGF blockade alone versus laser therapy alone. The results demonstrate that IAI given either every 4 or every 8 weeks (after 5 initial monthly doses) is superior to laser and results in both significant visual acuity gains and prevention of severe visual acuity loss. The primary efficacy endpoint (change from baseline in BCVA at 52 weeks) was superior in both 2q4 and 2q8 groups compared with the laser group in both

Acknowledgments

Assistance with the study design and conduct and data analysis was provided by Karen Chu, MS, and Xiaoping Zhu, PhD, Regeneron Pharmaceuticals, Inc. (VISTA), and Jana Sachsinger, PhD, and Christiane Norenberg, MS, Bayer HealthCare (VIVID). Editorial and administrative assistance to the authors was provided by Hadi Moini, PhD, and S. Balachandra Dass, PhD, Regeneron Pharmaceuticals, Inc.

References (13)

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The authors have made the following disclosures:

Jean-François Korobelnik: Advisory Board – Allergan, Alcon, Novartis; Consultant – Carl Zeiss Meditec, Roche, Thea; Fees (review activities) – Bayer HealthCare.

Diana V. Do: Research Funding – Genentech, Regeneron Pharmaceutical, Inc.

Ursula Schmidt-Erfurth – Consultant – Alcon, Bayer HealthCare, Boehringer, Novartis; Research Funding – Allergan, Alcon, Bayer HealthCare, Novartis; Travel Support – Bayer HealthCare.

David S. Boyer: Advisory Board Member – Alcon, Allergan, Neurotech; Consultant – Alcon, Allergo, Allergan, Bausch & Lomb, Bayer, KalVista, Neurotech, Novartis, Roche, ThromboGenics, GSK; Received Research funding – Genentech, Regeneron Pharmaceuticals, Inc.; Lecture Fee – Allergan.

Frank G. Holz: Consultant – Acucela, Alcon, Allergan, Bayer HealthCare, Boehringer-Ingelheim, Genentech, Heidelberg Engineering, Merz, Novartis, Pfizer; Research Funding –Alcon, Allergan, Bayer HealthCare, Carl Zeiss Meditec, GSK, Heidelberg Engineering, Novartis, Optos; Travel Support – Bayer HealthCare; Lecture Fees – Alcon, Bayer HealthCare, Heidelberg Engineering, Novartis, Pfizer.

Jeffrey S. Heier: Consultant – Acucela, Aerpio, Alcon, Allegro, Allergan, Bayer, Forsight Vision, Genentech, Genzyme, Kala Pharmaceutical, Liquidia, Merz, Neurotech, Ohr Pharmaceutical, Oraya, Regeneron Pharmaceuticals, Inc., Sanofi, Stealth Peptides, Thrombogenics, Xcovery; Research Funding – Acucela, Aerpio, Alcon, Alimera, Genentech, Genzyme, Kato Pharmaceutical, Lpath, Novartis, Ohr, Ophthotech, QLT, Regeneron Pharmaceuticals, Inc.

Edoardo Midena: Research Funding – Bayer HealthCare.

Peter K. Kaiser: Consultant to Bayer HealthCare, Chengdu Kanghong, Genentech, Novartis, Regeneron Pharmaceuticals, Inc.

Hiroko Terasaki: Research Funding – Alcon, Novartis, Pfizer, Santen, Senju, Wacamoto; Lecture Fees – Alcon, Bayer HealthCare, Novartis, Pfizer, Santen, Senju, Wacamoto.

Dennis M. Marcus: Consultant – Genentech, Thrombogenics, Regeneron Pharmaceuticals, Inc.; Research Funding – Regeneron Pharmaceuticals, Inc., Genentech, Thrombogenics, Alcon, Allergan, Ophthotech, GSK, Pfizer, Acucela, LPath, Quark.

Quan D. Nguyen: Research Funding – AbbVie, Genentech, Optos, Regeneron Pharmaceuticals, Inc., Santen, Inc.

Glenn J. Jaffe: Consultant – Heidelberg Engineering, Neurotech; Travel Support – Regeneron Pharmaceuticals, Inc.

Jason S. Slakter: Research Funding – Acucela, Alimera, Bayer HealthCare, Fovea, Genentech, Genzyme, GSK, Kanghong Biotech, LPath, Ohr Pharma, Oraya, Regeneron Pharmaceuticals, Inc., Sanofi, XcoveryVision; Equity Owner – SKS Ocular.

Christian Simader: Payments for masked data evaluation (institutional support, Vienna Reading Center) – Bayer HealthCare, Böhringer Ingelheim, Novartis.

Yuhwen Soo: Employee – Regeneron.

George D. Yancopoulos: Employee – Regeneron; Several patents issued and pending.

Neil Stahl: Employee – Regeneron; Several patents issued and pending.

Robert Vitti: Employee – Regeneron.

Alyson J. Berliner: Employee – Regeneron.

Thomas Schmelter: Employee – Bayer HealthCare.

Oliver Zeitz: Employee – Bayer HealthCare.

Carola Metzig: Employee – Bayer HealthCare.

David M. Brown: Consultant – Allergan, Bayer HealthCare, Genentech, Genzyme, Heidelberg Engineering, Notal Vision, Novartis, QLT, Regeneron, Thrombogenics; Research Funding – Abbott, Acucela, Alimera, Allergan, Ampio, Genentech, Genzyme, GSK, Novartis, Opthotech, Pfizer, pSivida, QLT, Quark, Regeneron Pharmaceuticals, Inc., Santen, Thrombogenics, Xoma; Travel Support – Regeneron Pharmaceuticals, Inc.

The VISTA and VIVID studies were funded by Regeneron Pharmaceuticals, Inc., Tarrytown, NY and Bayer HealthCare, Berlin, Germany. The sponsors participated in the design and conduct of the study, analysis of the data, and preparation of the manuscript.

The investigators from the VISTA and VIVID studies are listed in Appendix 1 (available at www.aaojournal.org).

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