Jordi Monés1, Sunil K Srivastava2, Glenn J Jaffe3, Ramin Tadayoni4, Thomas A Albini5, Peter K Kaiser2, Frank G Holz6, Jean-Francois Korobelnik7, Ivana K Kim8, Christian Pruente9, Timothy G Murray10, Jeffrey S Heier11. 1. Institut de la Màcula, Barcelona, Spain, Barcelona Macula Foundation, Barcelona, Spain. 2. Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. 3. Department of Ophthalmology, Duke University, Durham, North Carolina. 4. Departement Hospitalo-Universitaire Vision et Handicaps, Paris, France; Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Rothschild Foundation Hospital, Paris, France. 5. Bascom Palmer Eye Institute, The University of Miami, Miami, Florida. 6. Department of Ophthalmology, University of Bonn, Bonn, Germany. 7. CHU Bordeaux, Service d'ophtalmologie, Bordeaux, France; University Bordeaux, INSERM, BPH, Bordeaux, France. 8. Dr. Kim participated in this study as a consultant to Novartis independent of her faculty appointment in the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts. 9. Department of Ophthalmology, University of Basel, Basel, Switzerland; Department of Ophthalmology, Kantonsspital Baselland, Liestal, Switzerland; Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland. 10. Murray Ocular Oncology and Retina, Miami, Florida. 11. Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address: jsheier@eyeboston.com.
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.
RCT Entities:
PURPOSE: An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocularinflammation (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.
Authors: Muhammad Z Chauhan; Peyton A Rather; Sajida M Samarah; Abdelrahman M Elhusseiny; Ahmed B Sallam Journal: Cells Date: 2022-06-17 Impact factor: 7.666
Authors: Faruque Ghanchi; Rupert Bourne; Susan M Downes; Richard Gale; Christina Rennie; Ian Tapply; Sobha Sivaprasad Journal: Eye (Lond) Date: 2022-01-01 Impact factor: 4.456
Authors: Yuichiro Ogura; Glenn J Jaffe; Chui Ming Gemmy Cheung; Gregg T Kokame; Tomohiro Iida; Kanji Takahashi; Won Ki Lee; Andrew A Chang; Jordi Monés; Divya D'Souza; Georges Weissgerber; Kinfemichael Gedif; Adrian Koh Journal: Br J Ophthalmol Date: 2021-07-22 Impact factor: 5.908