1. Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER.
- Author
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Monés J, Srivastava SK, Jaffe GJ, Tadayoni R, Albini TA, Kaiser PK, Holz FG, Korobelnik JF, Kim IK, Pruente C, Murray TG, and Heier JS
- Subjects
- Aged, Angiogenesis Inhibitors administration & dosage, Angiogenesis Inhibitors adverse effects, Antibodies, Monoclonal, Humanized administration & dosage, Choroid pathology, Disease Progression, Double-Blind Method, Endophthalmitis diagnosis, Endophthalmitis epidemiology, Europe epidemiology, Female, Fluorescein Angiography, Follow-Up Studies, Fundus Oculi, Humans, Incidence, Intravitreal Injections, Male, Prognosis, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors, Recombinant Fusion Proteins, Retina pathology, Retinal Artery Occlusion diagnosis, Retinal Artery Occlusion epidemiology, Retinal Vasculitis diagnosis, Retinal Vasculitis epidemiology, Time Factors, United States epidemiology, Wet Macular Degeneration diagnosis, Antibodies, Monoclonal, Humanized adverse effects, Endophthalmitis etiology, Retinal Artery Occlusion etiology, Retinal Vasculitis etiology, Visual Acuity, Wet Macular Degeneration drug therapy
- Abstract
Purpose: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD)., Design: A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328)., Participants: Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes)., Methods: The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group., Main Outcome Measures: Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset., Results: Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%., Conclusions: This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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