Vision-Related Quality of Life in Patients with Diabetic Macular Edema Treated with Intravitreal Aflibercept: The AQUA Study

doi:10.1016/j.oret.2019.03.012

Ophthalmology Retina

Volume 3, Issue 7, July 2019, Pages 567-575

Presented as a poster at: EURETINA 2018 Congress, September 2018, Vienna, Austria; and as an abstract at: ISPOR Europe 2018 Congress, November 2018, Barcelona, Spain.

https://doi.org/10.1016/j.oret.2019.03.012 Get rights and content

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Purpose

To examine vision-related quality of life in patients with diabetic macular edema (DME) treated with intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Inc, Tarrytown, NY).

Design

AQUA was a multicenter, open-label, single-arm, phase 4 study.

Participants

Adults 18 years of age or older with type 1 or 2 diabetes mellitus and DME.

Methods

Patients received intravitreal aflibercept 2 mg every 8 weeks for 52 weeks, after 5 initial doses every 4 weeks.

Main Outcome Measures

The primary outcome was the change in 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) total score from baseline to week 52. Secondary outcomes included the change in NEI VFQ-25 near and distant activities subscale scores, best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and central retinal thickness (CRT) from baseline to week 52. Change in NEI VFQ-25 score at week 52 for better-seeing eyes (BSEs) and worse-seeing eyes (WSEs) also was evaluated.

Results

A total of 553 patients comprised the full analysis set, and 560 patients comprised the safety analysis set. At baseline, the mean NEI VFQ-25 total score was 70.12, mean BCVA was 61.5 ETDRS letters, and mean CRT was 464.81 μm. A mean of 8.8 injections were administered over 52 weeks. At week 52, the mean improvement from baseline in the NEI VFQ-25 total score was +6.11 (standard deviation [SD], 11.46); the corresponding improvements in near and distant activities were +11.37 (SD, 18.01) and +7.33 (SD, 17.32), respectively. Similarly, improvements in patients whose BSE and WSE were treated were 7.74 (SD, 13.59) and 5.48 (SD, 9.70), respectively. At week 52, mean change in BCVA was +10.0 ETDRS letters (SD, 8.0 ETDRS letters), and mean change in CRT was –175.38 μm (SD, 132.62 μm). Overall, 53.6% of patients reported treatment-emergent adverse events (TEAEs), of whom 26.8% experienced an ocular TEAE in the study eye. The most common serious ocular TEAE was endophthalmitis (0.5% [n = 3]). Five deaths (0.9%) were reported, but were not considered treatment related.

Conclusions

Intravitreal aflibercept was associated with clinically meaningful improvements in NEI VFQ-25 total score over 52 weeks in patients with DME; these were even more pronounced for near than for distant activities. Adverse events were consistent with the known safety profile of intravitreal aflibercept.

Abbreviations and Acronyms

ATE

arterial thrombotic event

BCVA

best-corrected visual acuity

BSE

better-seeing eye

confidence interval

CRT

central retinal thickness

DME

diabetic macular edema

DRSS

Diabetic Retinopathy Severity Scale

ETDRS

Early Treatment Diabetic Retinopathy Study

FAS

full analysis set

MCID

minimal clinically important difference

NEI VFQ-25

25-item National Eye Institute Visual Function Questionnaire

NPDR

nonproliferative diabetic retinopathy

PDR

proliferative diabetic retinopathy

QoL

quality of life

standard deviation

TEAE

treatment-emergent adverse event

VEGF

vascular endothelial growth factor

VISTA

Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema

VIVID

Intravitreal Aflibercept Injection in Vision Impairment due to DME

WSE

worse-seeing eye

Cited by (0)

: Supplemental material available at www.ophthalmologyretina.org.

: Financial Disclosure(s): The author(s) have made the following disclosure(s): J.G.G.: Consultant – Novartis, Bayer, Allergan, Alcon, AbbVie.

: J.S.: Consultant – Bayer, Novartis, Allergan.

: C.H.: Consultant – Bayer, Sanofi.

: T.S.: Employee and Equity owner – Bayer AG (Berlin, Germany).

: T.N.: Employee – Bayer AG (Berlin, Germany).

: O.S.: Employee – Bayer AG (Berlin, Germany) at the time this study was developed.

: S.S.: Consultant – Novartis, Bayer AG (Berlin, Germany), Allergan, Roche, Optos, Heidelberg Engineering, Boehringer Ingleheim.

: The AQUA study investigators: Alfredo Adan, Mikulas Alexik, Fareed Ali, Miguel Amaro, Vilma-Jurate Balciuniene, Francesco M. Bandello, Lluis Arias Barquet, Anna Beck, Katharina Bell, Francesco Boscia, Anniken Bures, Ângela Carneiro, David R. Chow, Andrius Cimbalas, Claudia Dahlke, Varma Deepali, John D. Dickinson, Michael Dollin, Chiara Eandi, Karl-Heinz Emmerich, Nicolas Feltgen, João Pereira Figueira, Oliver Findl, Monika Gajdošová, Richard P. Gale, Ivan John Galic, Justus Garweg, Vanessa Gasser-Steiner, Michel Giunta, John R. Gonder, Andrzej Grzybowski, Jan Hamouz, Lars-Olof Hattenbach, Frank G. Holz, Hasan Jesia, Jozef Kaluzny, Agnes Kerenyi, Peter J. Kertes, Frank Koch, Laurent Kodjikan, David E. Lederer, Ivana Liehneova, Katrin Lorenz, Andrew J. Lotery, Martin McKibbin, Geeta V. Menon, Zofia Michalewska, Edoardo Midena, Massimo Nicolo, Andras Papp, Gabriela Pavlovičová, Enrico Peiretti, Sara Vaz-Pereira, Paolo Perri, Ioannis Petropoulos, Frederic Queguiner, Krystyna Raczynska, Laura Sararols-Ramsay, Marek Rękas, Federico Ricci, Bozena Romanowska-Dixon, Helmut G. Sachs, Saddek Mohand-Said, Dirk Sandner, Ursula Schmidt-Erfurth, Walter Sekundo, Andras Seres, Sobha Sivaprasad, Eric Souied, João Castro de Sousa, Andrzej Stankiewicz, Jana Štefaničková, Katarína Struhárová, Jan Studnicka, Enrique Cervera Taulet, Simon Taylor, Slawomir Teper, Attila Vajas, Carlos Cava Valenciano, Balázs Varsányi, Francesco Viola, Gianni Virgili, Lars Wagenfeld, Gavin Walters, Peter Wiedemann, Tomasz Zarnowski.

: Supported by Bayer AG, Berlin, Germany. The sponsor or funding organization participated in the design of the study; conducting the study; data analysis; interpretation of the data; and preparation, review, and approval of the manuscript.

: Medical writing assistance was provided by Deepti Sharda and Melanie Meister-Broekema of PAREXEL, and was funded by Bayer.

: HUMAN SUBJECTS: Human subjects were included in this study. The study was conducted in 78 sites across 14 countries in Europe and Canada. Institutional review board or ethics committee approval was obtained at each site before, and informed consent to participate in the study was obtained from all patients. All information presented in this study complies with the Health Insurance Portability and Accountability Act for United States sites. The study was performed in accordance with the tenets of the Declaration of Helsinki.

: No animal subjects were included in this study.

: Author Contributions:

: Conception and design: Garweg, Stefanickova, Hoyng, Schmelter, Niesen, Sowade, Sivaprasad

: Analysis and interpretation: Garweg, Stefanickova, Hoyng, Schmelter, Niesen, Sowade, Sivaprasad

: Data collection: Garweg, Stefanickova, Hoyng, Sivaprasad

: Obtained funding: N/A

: Overall responsibility: Garweg, Stefanickova, Hoyng, Schmelter, Niesen, Sowade, Sivaprasad

^†: Deceased.

© 2019 by the American Academy of OphthalmologyThis is an open access article under the CC BY-NC-ND license ?(<inter-ref xlink: href=http://creativecommons.org/licenses/by-nc-nd/4.0/>http://?creativecommons.org/licenses/by-nc-nd/4.0/</inter-ref>).