Sterile intraocular inflammation associated with faricimab
The researchers identified 12 eyes of 7 patients (mean age, 73.3 years; 4 women) with noninfectious IOI after intravitreal faricimab injections.
(Image credit: AdobeStock/Celt Studio)
A new case series1 identified the development of sterile intraocular inflammation (IOI) following injections of faricimab (Vabysmo, Genentech) to treat age-related macular degeneration (AMD) or diabetic macular edema (DME), according to first author Mariano Cozzi, MSc, from the Department of Ophthalmology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, and the Eye Clinic, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
Mr. Cozzi and colleagues conducted an observational case series in 1 institution during which they presented and analyzed cases of IOI associated with faricimab treatment. The study included patients referred for IOI that developed shortly after administration of an intravitreal faricimab injection between June 1, 2022, and March 5, 2024.
The researchers commented, “IOI is a potential adverse event associated with intravitreal of anti-vascular endothelial growth factor (VEGF) agents. Although some cases of IOI may resolve without impacting visual function, others, especially those linked to retinal vasculitis, including occlusive retinal vasculitis, can lead to severe and irreversible visual loss.2,3. Therefore, it is crucial for international pharmacovigilance agencies to proactively prevent, detect, and comprehend adverse events and other undesirable outcomes related to medications. Recently, cases of IOI with occlusive vasculitis associated with faricimab have been reported in eyes that underwent anti-VEGF therapy.4,5 Based on the data available as of the end of August 2023, the estimated reported rate of retinal vasculitis with occlusion is 0.06 cases per 10 000 injections of faricimab.6,7
Case series
The patients had been treated with faricimab, 6 mg (0.05 mL of a 120-mg/mL solution), to treat either neovascular AMD or DME. Their systemic and ocular histories and imaging data from color fundus photographs, fluorescein angiograms, indocyanine green angiograms, and optical coherence tomography were evaluated for the following parameters: visual acuity measured with habitual correction using the Early Treatment of Diabetic Retinopathy Study charts before and after the event; intraocular pressure; patient symptoms; anterior, intermediate, or posterior location of the IOI; and the presence of retinal vasculitis.
The researchers identified 12 eyes of 7 patients (mean age, 73.3 years; 4 women) with noninfectious IOI after intravitreal faricimab injections.
Two eyes had retinal vasculitis together with anterior and posterior inflammation, and 1 of the 2 eyes had an occlusive form of vasculitis of the arteries and veins, leading to subsequent macular capillary nonperfusion and clinically relevant irreversible vision deterioration from 20/80 to 20/2000. The other 5 eyes had moderate anterior segment inflammation without substantial vision changes, Mr. Cozzi and colleagues reported.
The data analysis showed that the IOI developed after a median of 3.5 (interquartile range [IQR], 2.0-4.3) faricimab injections. The median (IQR) interval between the last faricimab injection and the IOI diagnosis was 28 (24-38) days. Three eyes had an increased in the intraocular pressure to 30 mmHg or higher
In commenting on their results, the investigators said, “Although these findings do not establish causality and can only generate hypotheses for future investigations, they underscore the importance of maintaining a high level of vigilance and attention when introducing new medications into routine clinical practice, especially when their safety profiles are not yet well established. Imaging is crucial for identifying and assessing the extent of inflammation, and prompt corticosteroid treatment tailored to the severity of the inflammatory response is recommended. Further data, derived from multicenter studies, are essential to provide additional insights into the safety and efficacy of faricimab in a larger patient population and to create clinical practice setting evidence. This is particularly important considering the restrictive inclusion criteria often used in randomized clinical trials, which may limit the generalizability of their safety findings.”
References
Cozzi M, Ziegler A, Fasler K, et al. Sterile intraocular inflammation associated with faricimab. JAMA Ophthalmol. 2024;Published online October 10, 2024. doi:10.1001/jamaophthalmol.2024.3828
Fine HF, Despotidis GD, Prenner JL. Ocular inflammation associated with antivascular endothelial growth factor treatment. Curr Opin Ophthalmol. 2015;26:184-187. doi:10.1097/ICU.0000000000000154
Anderson WJ, da Cruz NFS, Lima LH, et al. Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review. Int J Retina Vitreous. 2021;7(1):37. doi:10.1186/s40942-021-00307-7
Patterson T. Subject: VABYSMO (faricimab-svoa), new warning and precautions: retinal vasculitis and/or retinal vascular occlusion. Accessed May 25, 2024; https://www.gene.com/download/pdf/Vabysmo_DHCP_Important_Drug_Warning_2023-11-03.pdf
Chen X, Wang X, Li X. Intraocular Inflammation and occlusive retinal vasculitis following intravitreal injections of faricimab: a case report. Ocul Immunol Inflamm. Published online June 10, 2024. doi:10.1080/09273948.2024.2361834
Palmieri F, Younis S, Bedan Hamoud A, Fabozzi L. Uveitis following intravitreal injections of faricimab: a case report. Ocul Immunol Inflamm. Published online December 22, 2023. doi:10.1080/09273948.2023.2293925
Thangamathesvaran L, Kong J, Bressler SB, et al. Severe intraocular inflammation following intravitreal faricimab. JAMA Ophthalmol. 2024;142:365-370. doi:10.1001/jamaophthalmol.2024.0530
