Brolucizumab May Offer Anti-VEGF Nonresponders An Option

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Researchers report on early experiences of European patients who switched to brolucizumab therapy after undergoing other anti-VEGF injections.

Patients with neovascular age-related macular degeneration (nAMD) who have responded poorly to other anti-vascular endothelial growth factor (anti-VEGF) treatments may benefit from switching to brolucizumab, a study published in the British Journal of Ophthalmology suggests.

The use of anti-VEGF therapies has improved the vision of patients with nAMD, contributing to a reduction in the incidence of legal blindness, according to investigators. However, as patients live longer, repetitive intravitreal injections and office visits present a burden for both patients and their caregivers.

Brolucizumab, a single-chain antibody fragment, was approved in the US as a treatment for nAMD in February 2020. Potential benefits of the therapy are believed to be related to its low molecular weight, subsequent improved tissue penetration, and higher molar concentration.

Researchers examined the early real-world outcomes for patients who switched to brolucizumab therapy after previously receiving other anti-VEGF treatments. During the study, patients with recalcitrant nAMD were switched to brolucizumab therapy. Functional and structural parameters 4 weeks after first brolucizumab injection were evaluated, including best-corrected visual acuity (BCVA (logMAR)), foveal center point (FCP (μm)), central subfield retinal thickness (CSRT (μm)), and macular volume (mm³). The study pool included 63 eyes of 57 patients with nAMD (52.6% females) with a mean (±SD) age of 79.5±6.7 years. Investigators noted a mean change in BCVA of −0.02±0.13 logMAR (P =.322), a mean change in FCP of -66.79±72.64 μm, -66.76±60.71 μm for CSRT, and -0.27±0.24 mm³ for macular volume (all P <.001). Intraocular inflammation was observed in 7 eyes of 7 patients, including 1 case of retinal vasculitis without occlusion. The team concluded that further long-term analyses in routine clinical settings are warranted.

“A beneficial morphological effect was recorded pointing towards a strong antihyperpermeability effect of this agent,” the report shows. However, the investigators add that safety issues regarding the agent’s association with intraocular inflammation persist and require additional investigation.  

The study’s authors noted some limitations to their work, including its relatively small cohort of 57 patients and the short review period post-switch to brolucizumab of 1 month. In this study, investigators applied a treat-and-extend scheme immediately after the first injection. They did not perform 3 fixed 4-weekly injections post switch to brolucizumab as proposed in other switch studies. Furthermore, no treatment-naïve patients were investigated, and the study cannot address the questions of potentially longer durability of brolucizumab compared with other anti-VEGF agents during a treat-and-extend regimen.

Disclosure: Some study authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.  


Bulirsch LM, Saßmannshausen M, Nadal J, et al. Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study. Br J Ophthalmol. Published Online April 12, 2021. doi:10.1136/bjophthalmol-2020-318672