Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes: A Randomized Clinical Trial
Jeffrey S Heier, David M Brown, Sumit P Shah, Namrata Saroj, Sabin Dang, Nadia K Waheed, Charles C Wykoff, Jonathan L Prenner, David S Boyer, Jeffrey S Heier, David M Brown, Sumit P Shah, Namrata Saroj, Sabin Dang, Nadia K Waheed, Charles C Wykoff, Jonathan L Prenner, David S Boyer
Abstract
Importance: Anti-vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss.
Objective: To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months.
Design, setting, and participants: This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to <125 μm), at least 1 large druse (≥125 μm), and/or retinal pigmentary changes, and eAMD in the fellow eye. Patients were treated from June 23, 2015, to March 13, 2019.
Interventions: Intravitreal aflibercept injection (2 mg) or sham quarterly injection for 24 months (1:1 randomization).
Main outcomes and measures: The primary end point was the proportion of patients with conversion to eAMD at month 24 characterized by development of choroidal neovascularization, as assessed by leakage on fluorescein angiography and fluid on spectral-domain optical coherence tomography by an independent masked reading center.
Results: Of 128 patients enrolled, 127 (63 in the IAI group and 64 in the sham group) were included in the primary analysis (68 men [53.5%]; mean [SD] age, 76.5 [8.1] years). Baseline demographic and clinical characteristics were balanced between the groups. By month 24, 6 patients (9.5%) in the IAI group and 7 (10.9%) in the sham group developed eAMD (P = .98). Patients with a history of eAMD for longer than 2 years in their fellow eye at baseline showed a lower rate of conversion to eAMD in the study eye compared with those with a history of eAMD for 2 years or less in the fellow eye. Safety was consistent with previous studies involving intravitreal anti-VEGF injections.
Conclusions and relevance: In this evaluation of quarterly anti-VEGF exposure as prophylaxis to reduce conversion of eyes with high-risk dry AMD to eAMD, the rates of conversion were not lower in the IAI group compared with the sham treatment group at month 24. Understanding the mechanism of conversion to eAMD and therapies that could prevent this event remains an important unmet need.
Trial registration: ClinicalTrials.gov Identifier: NCT02462889.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Heier reported consulting for 4D Molecular Therapeutics, Adverum Biotechnologies, Inc, Aerie Pharmaceuticals, Inc, Aerpio, Aldeyra Therapeutics, Inc, Allegro Ophthalmics, LLC, Alzheon, Inc, Annexon, Inc, Apellis Pharmaceuticals, AsclepiX Therapeutics, Beaver-Visitec International, Galimedix Therapeutics, Inc, Genentech, Inc, GyroscopeTx, iRenix Medical, Inc, jCyte, Inc, Kala Pharmaceuticals, Kanghong Pharmaceuticals, NGM Biopharmaceuticals, Notal Vision, Inc, Novartis AG, Ocugenix, Oculis, Ocunexus Therapeutics, Inc, Ocular Therapeutix, Inc, Palatin Technologies, Inc, Pfizer Inc, Regeneron Pharmaceuticals, Inc, REGENXBIO Inc, Santen Pharmaceutical Co, Ltd, SciFluor Life Sciences, Shire Plc, Stealth BioTherapeutics Inc, Tyrogenex, and Voyant; receiving research funding from Aerie Pharmaceuticals, Inc, Aerpio, Apellis Pharmaceuticals, Genentech, Inc, Graybug Vision, Inc, GyroscopeTx, Hemera Biosciences LLC, R&D for Janssen Global Services, LLC, KalVista Pharmaceuticals, Kanghong Pharmaceuticals, Novartis AG, Ophthotech Corporation, Optovue, Incorporated, Regeneron Pharmaceuticals, Inc, REGENXBIO Inc, and Stealth BioTherapeutics Inc; and having equity in Adverum Biotechnologies, Inc, Aldeyra Therapeutics, Inc, Allegro Ophthalmics, LLC, Aviceda Therapeutics, Digital Surgery Systems, jCyte, Inc, and Ocular Therapeutix, Inc. Dr Brown reported consulting for Genentech/Roche, Regeneron Pharmaceuticals, Inc, Bayer AG, Novartis AG, Allergan, Senju Pharmaceutical Co, Ltd, Apellis Pharmaceuticals, Adverum Biotechnologies, Inc, Boehringer Ingelheim, Clearside Biomedical, REGENXBIO Inc, Santen Pharmaceutical Co, Ltd, Zeiss, Optos plc, Heidelberg Pharma AG, Kodiak Sciences Inc, Lineage Cell Therapeutics, Inc, Ocular Therapeutix, Inc, Stealth BioTherapeutics Inc, Celltrion, and Chengdu Kanghong Pharmaceutical Group Co, Ltd, and receiving research funding from Genentech/Roche, Regeneron Pharmaceuticals, Inc, Bayer AG, Novartis AG, Allergan, Senju Pharmaceutical Co, Ltd, Apellis Pharmaceuticals, Adverum Biotechnologies, Inc, Boehringer Ingelheim, Clearside Biomedical, REGENXBIO Inc, Santen Pharmaceutical Co, Ltd, Zeiss, Optos plc, Heidelberg Pharma AG, Kodiak Sciences Inc, Stealth BioTherapeutics Inc, and Chengdu Kanghong Pharmaceutical Group Co, Ltd. Dr Shah reported receiving research funding and speaker fees from Regeneron Pharmaceuticals, Inc, and Genentech/Roche. Dr Dang reported receiving speaker fees from Regeneron Pharmaceuticals, Inc. Dr Waheed reported consulting for Topcon Corporation, Genentech/Roche, Regeneron Pharmaceuticals, Inc, Apellis Pharmaceuticals, Astellas, Boehringer Ingelheim, and Novartis AG and having equity in Boston Imaging Reading Center. Dr Wykoff reported consulting for Acuela, Adverum Biotechnologies, Inc, Aerpio, Alimera Sciences, Allegro Ophthalmics, LLC, Allergan, Apellis Pharmaceuticals, Bayer AG, Chengdu Kanghong Pharmaceutical Group Co, Ltd, Clearside Biomedical, DORC (Dutch Ophthalmic Research Center), EyePoint Pharmaceuticals, Genentech/Roche, GyroscopeTx, IVERIC bio, Kodiak Sciences Inc, Novartis AG, ONL Therapeutics, Oxurion NV, PolyPhotonix, Recens Medical, Regeneron Pharmaceuticals, Inc, REGENXBIO Inc, Santen Pharmaceutical Co, Ltd, and Takeda Pharmaceutical Company Limited and receiving research funding from Adverum Biotechnologies, Inc, Aerie Pharmaceuticals, Inc, Aerpio, Alimera Sciences, Allergan, Apellis Pharmaceuticals, Chengdu Kanghong Pharmaceutical Group Co, Ltd, Clearside Biomedical, Gemini Therapeutics, Genentech/Roche, Graybug Vision, Inc, GyroscopeTx, Ionis Pharmaceuticals, IVERIC bio, Kodiak Sciences Inc, Neurotech LLC, Novartis AG, Opthea, Outlook Therapeutics, Inc, Recens Medical, Regeneron Pharmaceuticals, Inc, REGENXBIO Inc, Samsung Pharm Co, Ltd, Santen Pharmaceutical Co, Ltd, and Xbrane Biopharma AB. Dr Prenner reported consulting for Alcon and Regeneron Pharmaceuticals, Inc. Dr Boyer reported consulting for Acucela, Inc, Aerpio, Alcon, Allegro Ophthalmics, LLC, Allergan, Amydis, Inc, Bausch & Lomb Incorporated, Bayer AG, BioMotiv, Boehringer Ingelheim, Clearside Biomedical, CoDa Therapeutics, Inc, Foresight Bioscience, Inc, Genentech, Inc, Gensight Biologics, Glaukos Corporation, GlaxoSmithKline plc, Graybug Vision, Inc, Ionis Pharmaceuticals, Isarna Therapeutics, Kala Pharmaceuticals, Notal Vision, Inc, Neurotech LLC, Novartis AG, Ocular Therapeutix, Inc, Ophthotech Corporation, Ohr Pharmaceutical, Inc, Optos plc, Optovue Incorporated, Ora Pharm Ltd, pSivida, Regeneron Pharmaceuticals, Inc, Regulus Therapeutics Inc, River Vision, F. Hoffmann-La Roche AG, Santen Pharmaceutical Co, Ltd, Shire plc, Stealth BioTherapeutics Inc, Sun Pharmaceutical Industries Ltd, Taiwan Liposome Company, Ltd, and ThromboGenics, Inc, and receiving research funding from Alcon, Allergan, Genentech, Inc, Novartis AG, Neurotech LLC, Pfizer Inc, Regeneron Pharmaceuticals, Inc, and Santen Pharmaceutical Co, Ltd. No other disclosures were reported.
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Source: PubMed