Brolucizumab-related intraocular inflammation in Japanese patients with age-related macular degeneration: a short-term multicenter study

Abstract

Dear Editor, We report short-term data on the development of intraocular inflammation (IOI) after intravitreal brolucizumab injection for exudative age-related macular degeneration (AMD) in Japanese patients in this letter. Brolucizumab (Novartis Pharma AG, Basel, Switzerland), a new anti-vascular endothelial growth factor (VEGF) agent for the treatment of exudative AMD, differs from previous anti-VEGF agents by its smaller molecular weight allowing administration at high concentrations and presumably improved tissue penetration. In the HAWK and HARRIER studies, brolucizumab was reportedly non-inferior to aflibercept in terms of visual outcomes and more effective in reducing intraretinal and subretinal fluid [1]. Early US reports regarding the adverse effect of IOI [2] prompted a Novartis-appointed Safety Review Committee (SRC) to re-evaluate data from the clinical trials [3]. At the 2020 Annual Meeting of the American Academy of Ophthalmology, Heier et al. [4] described SRC findings suggesting that female gender and Japanese ethnicity were risk factors.

Risk factors for emerging intraocular inflammation after intravitreal brolucizumab injection for age-related macular degeneration

“…Tendency and female dominance were similar to those reported previously. However, Maruko reported that IOI was detected in 9% (4/43 eyes) of treatment-naïve patients and 10% in a switched group, and in his report, no sex-related disease association was observed [ 19 ].…”

Short-Term Efficacy and Safety Outcomes of Brolucizumab in the Real-Life Clinical Practice

“…Overall, the safety profile of IVT-B in our cohort is in accordance with the post-hoc analysis of the study HAWK and HARRIER, where in eyes treated with 6 mg brolucizumab, the incidence of IOI reported by the investigators was at least 4.6%, with the 48% of the IOI occurring within the first 3 months ( Monés et al, 2020 ). Several case reports described intraocular inflammation (IOI), retinal vasculitis and/or retinal artery occlusion associate with severe visual acuity loss within the first 3 months after IVT-B ( Baumal et al, 2020 ; Kondapalli et al, 2020 ; Sharma et al, 2020b ; Maruko et al, 2021 ). Therefore, the ophthalmic community is aware of these potential severe adverse events and a post-marketing reporting system actively collects the AEs and will help to determine the figures of this concern in real-life clinical practice ( www.brolucizumab.info ).…”

“…Clinical data regarding the use of intravitreal injections of brolucizumab (IVT-B) outside the above-mentioned clinical trials are still limited. To our knowledge, there are only a few brief reports that investigated the real-world efficacy and safety of brolucizumab ( Avayon et al, 2020 ; Bulirsch et al, 2021 ; Maruko et al, 2021 ; Sharma et al, 2021 ), thus our investigation aims to report our real-life experience with this new anti-VEGF agent in a cohort of nAMD patients.…”

Long-term characteristics of exudative age-related macular degeneration in Japanese patients

“…A newly anti-VEGF drug brolucizumab is the smallest molecule weight of a 28 kDa humanized single-chain antibody fragment and has been approved to use unprecedented 12-week dosing schedule, which can be able to achieve dry macular and prevent frequent visits for AMD patients [ 10 , 11 ]. However, IOI after injection of brolucizumab has been reported to be incidence of 4.7 to 19% [ 10 , 40 , 41 ]. Therefore, it should be needed that the different proper use of anti-VEGF drugs using ranibizumab, aflibercept and brolucizumab according to CNV subtypes.…”

“…incidence of 4.7 to 19% [10,40,41]. Therefore, it should be needed that the different proper use of anti-VEGF drugs using ranibizumab, aflibercept and brolucizumab according to CNV subtypes.…”