Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2022 Jan 1;140(1):20-28.
doi: 10.1001/jamaophthalmol.2021.4585.

Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration: Results From the IRIS Registry and Komodo Healthcare Map

Arshad M Khanani  1   2 , Marco A Zarbin  3 , Mark R Barakat  4 , Thomas A Albini  5 , Peter K Kaiser  6 , Guruprasad B  7 , Neetu Agashivala  7 , Justin S Yu  7 , Charles C Wykoff  8   9 , Mathew W MacCumber  10   11
Affiliations
Comment

Safety Outcomes of Brolucizumab in Neovascular Age-Related Macular Degeneration: Results From the IRIS Registry and Komodo Healthcare Map

Arshad M Khanani et al. JAMA Ophthalmol. .

Abstract

Importance: Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu).

Objective: To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated.

Design, setting, and participants: This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included.

Intervention: Brolucizumab injections.

Main outcome and measures: Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors.

Results: Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events.

Conclusions and relevance: The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Khanani has received personal fees from 4DMT, Adverum, Aerpio, Allergan, Apellis, Broadwing Bio, Chengdu Kanghong, DORC, Genentech, Glaukos, Gyroscope, Gemini Therapeutics, Graybug, Iveric Bio, Kato Pharmaceuticals, Kodiak, Nanoscope, Novartis, Opthea, Oxurion, Polyphotonix, Recens Medical, Regenxbio, Surrozen, and Unity; has received grant support from Adverum, Alkahest, Allergan, Annexon, Apellis, Asclepix, Chengdu Kanghong, Genentech, Gyroscope, Gemini Therapeutics, Graybug, Kato Pharmaceuticals, Kodiak, NGM Biopharmaceuticals, Novartis, Iveric Bio, Opthea, Oxurion, Ocular Therapeutics, Recens Medical, Roche, Regenxbio, and Unity; and has received nonfinancial support from Novartis. Dr Zarbin is a consultant for Boehringer Ingelheim, Frequency Therapeutics, Genentech/Roche, Iduna, Iveric Bio, Life Biosciences, Novartis Pharma AG, Ophthotech, Perfuse Therapeutics, and Selphagy; has received grants from Aerie Pharmaceutical; is an equity owner in Frequency Therapeutics, Iveric Bio, NVasc; and is a co-founder of NVasc. Dr Barakat is a consultant for Adverum Biotechnologies, Alcon, Allegro, Allergan, Alimera, Bausch & Lomb, Clearside Biomedical, Inc, EyePoint Pharmaceuticals, Kodiak Sciences, Genentech/Roche, Graybug, Novartis, Ocular Therapeutix, Palatin Technologies, Regeneron, and REGENXBIO; is a speaker for Genentech/Roche, Novartis, and Regeneron; reported nonfinancial support from Novartis; and has stock in Oxurion. Dr Albini is a consultant for Adverum Biotechnologies, Allergan, Beaver Visitec, Applied Genetic Technologies Corporation, Clearside Biomedical Inc, Eyepoint Pharmaceuticals Inc, Genentech, Novartis, REGENXBIO, and Valeant Pharmaceuticals. Dr Kaiser is a consultant for Allegro, Allergan, AsclepiX, Bayer, Bausch Health, Biogen Idec, Boehringer Ingelheim, Carl Zeiss Meditec, Clearside Biomedical, DTx Pharma, Duet Therapeutics, Eyevensys, Glaukos, Innovent, iRenix, IvericBio, Kanghong, Kodiak, Novartis, Regeneron, RegenxBio, Samsung Bioepis, and Sandoz. Drs B and Yu and Ms Agashivala are employees of Novartis Pharmaceuticals Corporation. Ms Agashivala is also a shareholder of Novartis Pharmaceuticals Corporation. Dr Wykoff is a consultant for Adverum, Aerie, Aerpio, Alimera Sciences, Allegro, Allergan Inc, Allgenesis, Alnylam, Apellis, Arrowhead, Bausch & Lomb, Bayer Healthcare, Bionic Vision Technologies, Chengdu Kanghong Biotechnologies, Clearside Biomedical, Inc, DORC, EyePoint, Genentech/Roche, Gyroscope, Ionis, Iveric Bio, Janssen, Kato, Kodiak, Long Bridge Medical, NGM, Notal Vision, Novartis (US and AG Basel), OccuRx, Ocular Therapeutix, ONL Therapeutics, Opthea Limited, Palatin, PolyPhotonix, Recens Medical, Regeneron, Regenxbio, Roche, Santen, Surrozen, Takeda, Verana Heath, and Vitranu and involved with research for Adverum, Aerie, Aerpio, Allergan, Amgen, Apellis, Asclepix, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies, Clearside, Biomedical, EyePoint, Gemini, Genentech/Roche, Graybug Vision, Gyroscope, Ionis, iRENIX, Iveric Bio, LMRI, Neurotech, Novartis (US and AG Basel), NGM, Novartis, Opthea, Oxurion, RecensMedical, Regeneron, Regenxbio, Roche, SamChunDang, Samsung Bioepis, Santen, Taiwan Liposome Company, and Xbrane BioPharma. He also reported other support from ONL Therapeutics, PolyPhotonix, RecensMedical, and Visgenx. Dr MacCumber is a consultant for Alimera Sciences, Genentech/Roche, Novartis Pharma AG, Regeneron, Spark Therapeutics, received grant support from Alimera Sciences, Apellis, Gemini Therapeutics, Clearside Biomedical, and the National Eye Institute, as well as an equity owner in Covalent Medical and US Retina. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Identification of Potential Risk Factors at Baseline on Estimated Incidence of Any Form of Intraocular Inflammation (Including Retinal Vasculitis) and/or Retinal Vascular Occlusion, Based on a Multivariable Model
Retinal vascular occlusion is inclusive of retinal vein occlusion and retinal artery occlusion. Follow-up days variable was used to adjust for varying length of follow-up; graphs are plotted to logarithmic scale. Odds ratio (OR) greater than 1 indicates increased risk of intraocular inflammation and/or retinal vascular occlusion, and an OR less than 1 indicates a decreased risk of intraocular inflammation and/or retinal vascular occlusion. Retinal vascular occlusion represents any form of intraocular inflammation (including retinal vasculitis and retinal vascular occlusion; 255 patient eyes [2.4%] in the Intelligent Research in Sight [IRIS] Registry and 268 patient eyes [2.4%] in the Komodo database). Anti-VEGF indicates anti–vascular endothelial growth factor; ref., reference.
Figure 2.
Figure 2.. Identification of Potential Risk Factors at Baseline on Estimated Incidence of Retinal Vasculitis and/or Retinal Vascular Occlusion Based on a Multivariable Model
Retinal vascular occlusion is inclusive of retinal vein occlusion and retinal artery occlusion. The follow-up days variable was used to adjust for varying length of follow-up; graphs are plotted to logarithmic scale, odds ratios (ORs) greater than 1 indicate increased risk of intraocular inflammation and/or retinal vascular occlusion, and ORs less than 1 indicate a decreased risk of intraocular inflammation and/or retinal vascular occlusion. Retinal vascular occlusion represents retinal vasculitis and/or retinal vascular occlusion (59 patient eyes [0.6%] in the Intelligent Research in Sight [IRIS] Registry and 63 patient eyes [0.6%] in the Komodo database). Anti-VEGF indicates anti–vascular endothelial growth factor; ref., reference.
Figure 3.
Figure 3.. Model-Based Estimation of Incidence Rate for Any Form of Intraocular Inflammation (IOI; Including Retinal Vasculitis) and/or Retinal Vascular Occlusion (RO) Based on Identified Risk Factors at Baseline
Retinal vascular occlusion is inclusive of retinal vein occlusion and retinal artery occlusion. Based on 12-month history data, in patient eyes with up to 6 months of follow-up. Estimates for risk (95% CIs) were adjusted for age, prior anti–vascular endothelial growth factor treatment and length of follow-up. IOI indicates intraocular inflammation; IRIS, Intelligent Research in Sight.
Figure 4.
Figure 4.. Model-Based Estimation of Incidence Rate for Retinal Vasculitis and/or Retinal Vascular Occlusion (RO), Based on Identified Risk Factors at Baseline
Retinal vascular occlusion is inclusive of retinal vein occlusion and retinal artery occlusion. Based on 12-month history data, in patient eyes with up to 6 months of follow-up. Estimates for risk (95% CIs) were adjusted for age, prior anti–vascular endothelial growth factor treatment, and length of follow-up. IOI indicates intraocular inflammation; IRIS, Intelligent Research in Sight.
See this image and copyright information in PMC

Comment on

References

    1. Centers for Disease Control and Prevention . Common eye disorders. Updated June 3, 2020. Accessed October 15, 2020. https://www.cdc.gov/visionhealth/basics/ced/index.html
    1. Flaxel CJ, Adelman RA, Bailey ST, et al. . Age-Related Macular Degeneration Preferred Practice Pattern®. Ophthalmology. 2020;127(1):1-P65. doi:10.1016/j.ophtha.2019.09.024 - DOI - PubMed
    1. Novartis Pharmaceuticals Corporation . Beovu package insert. Published 2020.
    1. Yannuzzi NA, Freund KB. Brolucizumab: evidence to date in the treatment of neovascular age-related macular degeneration. Clin Ophthalmol. 2019;13:1323-1329. doi:10.2147/OPTH.S184706 - DOI - PMC - PubMed
    1. Dugel PU, Koh A, Ogura Y, et al. ; HAWK and HARRIER Study Investigators . HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72-84. doi:10.1016/j.ophtha.2019.04.017 - DOI - PubMed

Publication types

Substances