Brolucizumab Appears to Have ‘Drying’ Effect in Neovascular AMD, Short Study Finds

NEW YORK (Reuters Health) – Patients with neovascular age-related macular degeneration (nAMD) who receive intravitreous injection (IVI) with brolucizumab have stable visual acuity over the short term and show a drop in central-subfield thickness, according to a new case series.

To examine early experience with the drug, an anti-vascular endothelial growth factor (VEGF) approved by the U.S. Food and Drug Administration in 2019, Dr. David A. Eichenbaum of Retina-Vitreous Associates of Florida, in Tampa, and colleagues looked at data from 15 ophthalmological centers.

“Our publication reflects today’s real-world brolucizumab use in mostly treatment-experienced eyes,” Dr. Eichenbaum told Reuters Health by email. “Many of these eyes are under-performing on other drugs, and our results emphasize the drying effects of brolucizumab in this population.”

The study evaluated the experience of six retina specialists who were early adopters of brolucizumab. In total, 172 eyes from 152 patients with a mean age of 80 years were included. Most (166) had had prior treatment including 109 who switched from their previous anti-VEGF agent mainly because of persistent fluid seen on optical coherence tomography (OCT).

Study eyes were given a mean of 1.46 intravitreous injections, and the median time between the last brolucizumab IVI and final study evaluation was 42.5 days. Additional follow-up was limited owing to COVID-19 pandemic restrictions.

Mean visual acuity before starting brolucizumab as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, was 64.1. At the last evaluation, it was 63.3, the researchers report in JAMA Ophthalmology.

After allowing for factors such as the presence of fluid or intraocular inflammation there was still no difference in mean visual acuity during the study or at its completion.

The mean central-subfield thickness in all eyes before starting brolucizumab was 296.7 um and fell significantly to 269.8 um at the last study examination (P=0.003).

Intraocular inflammation was reported in 14 eyes from 13 patients. None had had a history of inflammation associated with another anti-VEGF agent. Severity was deemed mild in 10 eyes, moderate in three and severe in only one involving occlusive retinal vasculitis.

Measures to resolve anterior and vitreous inflammation included corticosteroid eyedrops, but six cases resolved without treatment.

Risk factors apparently associated with intraocular inflammation were bilateral same-day brolucizumab IVI (relative risk, 1.72) and being female (RR, 1.27). There was no correlation with the previous number of anti-VEGF IVIs.

The pandemic affected the ability of patients to return for prolonged follow-up examinations, but in 65 eyes (37.8%), brolucizumab treatment was stopped by the physician and switched to another anti-VEGF therapy.

The risk of developing intraocular inflammation of any severity and losing 15 or more letters was 1.2% (2 of 172) in the current study compared to 0.7% (8 of 1,088) in a previous study.

As Dr. Eichenbaum pointed out, “Intraocular inflammation remains a concern with use; although the rate in our study was higher than that in the registration trials, most events were mild and many were self-limited. Rare severe inflammatory events associated with vision loss can occur.”

Dr. Jason Hsu, co-director of Retina Research at Wills Eye Hospital, in Philadelphia, told Reuters Health by email, “On first glance, the optical coherence tomography findings appear to show an improvement in macular edema after switching. However, without a matched control group that was not switched, it is impossible to ascertain whether this is a real drug effect or the natural course of continuing any anti-VEGF drug where there can be waxing and waning of edema from visit to visit, which may also be dependent on the amount of time between injections.”

“The study,” added Dr. Hsu, who was not involved in the study, “also describes intraocular inflammatory events after brolucizumab which has been a major concern in the retina community due to early reports of multiple cases of occlusive retinal vasculitis, which is severe inflammation in the retinal blood vessels leading to lack of blood flow to the retina and sometimes severe vision loss. Due to the small number of eyes that developed inflammation in this study, it is difficult to draw any conclusions about the true incidence, nature, and risk factors.”

In an email to Reuters Health, Dr. Shriji N. Patel, an assistant professor of ophthalmology at Vanderbilt Eye Institute, in Memphis, Tennessee, also homed in on the subject of inflammation, noting, “Though most cases were mild and self-limited, the risk of severe vision loss due to occlusive vasculitis remains a cause for concern.”

Dr. Patel was not involved in the study.

Dr. Eichenbaum and some of his coauthors report financial ties to Novartis, which markets brolucizumab as Beovu.

SOURCE: JAMA Ophthalmology, online February 25, 2021.

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