The majority of patients with wet age-related macular degeneration (AMD) who initiated therapy with brolucizumab did so after prior anti-vascular endothelial growth factor (VEGF) therapy, according to a real-world analysis from the Intelligent Research in Sight (IRIS) registry. Michael S. Ip, MD, of Doheny Eye Institute, presented results from the registry at the American Academy of Ophthalmology 2020 Virtual meeting.
“Phase III clinical trials have shown that brolucizumab is an effective therapy option in exudative AMD, with the potential to extend injection intervals and the majority of patients experience benefit without severe adverse events (AEs),” Dr. Ip said.
However, currently, there are limited data regarding real-world characteristics and outcomes of patients with wet AMD who were treated with brolucizumab. To find out more, Dr. Ip and colleagues analyzed data from the IRIS registry. Specifically, they looked at safety outcomes for intraocular inflammation and/or retinal vascular occlusion.
Looking at the safety results of the HAWK and HARRIER trials, which compared brolucizumab with aflibercept, the safety of the two drugs was similar with the exception of intraocular inflammation, which was seen at a numerically higher rate with brolucizumab.
As a result, the label for brolucizumab was updated to include intraocular inflammatory events and Novartis, the drug’s manufacturer, initiated its own internal review of these post-marketing safety case reports. The external Safety Review Committee confirmed a safety signal of rare AEs termed as retinal vasculitis and/or retinal vascular occlusion that may result in severe vision loss. The overall incidence of intraocular inflammation of any form was 4.6%. The overall incidence of retinal vasculitis was 3.3%, and the incidence of concomitant signs of retinal vasculitis and retinal vascular occlusion was 2.1%.
In this real-world study, Dr. Ip and colleagues looked at more than 12,000 patients treated with brolucizumab between October 2019 and June 2020. They found that 90.0% of these eyes had prior treatment with anti-VEGF, “suggesting unmet medical needs continue to exist for patients that have wet AMD that are treated with our current anti-VEGF therapies.” Additionally, the anti-VEGF used most immediately prior to the switch was aflibercept (73.9%).
Up to six months after first brolucizumab injection, no intraocular inflammation, retinal vasculitis, or retinal vascular occlusion was seen in 97.61% of patients. All forms of intraocular inflammation occurred in 2.39% of patients, and retinal vasculitis and/or retinal vascular occlusion occurred in 0.55%.
Dr. Ip noted that these observed events were identified using ICD diagnostic codes. Actual causality to the use of brolucizumab remains undetermined.
The researchers found that prior ocular inflammation or prior occlusion (odds ratio [OR], 4.69) and female gender (OR, 2.23) were most associated with inflammatory events. Additionally, there was an increase in the observed risk rate in certain populations. Specifically, patients with prior intraocular inflammation or occlusion, whether male or female, was driving the increase in risk rate for intraocular inflammation. This was also found for the risk rate of retinal vasculitis and/or retinal occlusion.