After FDA approval of the anti-VEGF drug brolucizumab (Beovu) in 2019, for the treatment of wet age-related macular degeneration (AMD), reports surfaced of intraocular inflammation (IOI) among patients prescribed the medication. To learn more, researchers in France examined the risk of IOI following the treatment with the drug. Their study showed an IOI incidence rate of 10.5% with brolucizumab use, highlighting the need for monitoring and education.1
AFTER BROLUCIZUMAB. Color fundus photograph shows perivascular sheathing and retinal whitening.
Study details. For the study, a team at the Sorbonne University in Paris and several other academic medical centers in France, collaborated with Beovu-maker Novartis on a prospective phase 3b single-arm, open-label, multicenter study. They followed two sets of patients being treated with brolucizumab for AMD. One group had been previously treated with ranibizumab or aflibercept, while the other set had never received anti-VEGF treatment.
Findings. In total, 505 patients were treated with brolucizumab. Of these, 53 had at least one IOI-related event, an incidence of 10.5%. The majority of these cases (81%) occurred during the loading phase, or first three months of treatment. The most frequently reported symptoms included floaters, blurred vision, and decreased vision.
Once IOI was identified, the affected patients promptly stopped receiving brolucizumab therapy. Most were treated with corticosteroids—28.3% were given systemic steroids and 26.8% were given intraocular steroids—which completely resolved the inflammation for most patients. Two patients experienced severe vision loss related to retinal complications. The researchers noted no difference in the rate of adverse effects between patients who had been previously treated with anti-VEGFs and those who had never been treated. The researchers said: “Given the higher drying effect and longer treatment duration with brolucizumab, the risk-benefit ratio remains favorable, as long as ophthalmologists observe the precautions for use from the prescribing notice.”
A caution. But retina specialist Gregg T. Kokame, MD, at the University of Hawaii, Honolulu, who was not involved in the study, said he has concerns. “Brolucizumab has a better response than aflibercept in the drying effect of subretinal fluid and macular edema, but the risk of inflammation limits its use,” he said. “The risk of severe vision loss, although very rare, does affect the decision on whether or not to use brolucizumab.” He noted that although the majority of IOI cases occurred during the loading phase, “inflammation can occur much later and as long as two months after the last injection.” Dr. Kokame and the researchers emphasized the importance of both physician and patient monitoring for IOI when using brolucizumab.
Ophthalmologists should “educate patients carefully on the symptoms of inflammation, for example, redness, pain, floaters, photophobia, and decreased vision,” Dr. Kokame said, adding that patients should be evaluated by an ophthalmologist immediately if symptoms develop. Because most inflammation cases occurred after the first three brolucizumab injections, he said, “Be especially vigilant about exams for inflammation and patient symptoms during this time.”
Dr. Kokame noted that while the treatment of wet AMD “has markedly advanced” with anti-VEGF agents, the financial costs and frequent office visits are a tremendous burden on patients and the health care system. “Any treatment that can successfully extend the duration of treatment while still maintaining efficacy is the most important future goal,” he said, pointing to current studies looking at the potential for gene therapy that involves intravitreal, subretinal, and suprachoroidal methods of administration.
1 Bodaghi B et al. Ophthalmol Retina. Published online June 19, 2023.
Relevant financial disclosures: Dr. Kokame—None.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Kokame Adverum: S; Bausch + Lomb: C; Carl Zeiss Meditec: C; Genentech: S; Hoffman LaRoche: C; Iveric Bio: S; Novartis: S; Regeneron: S; RegenxBio: S; Salutaris: S.
Dr. Tan None.
Dr. Yohannan AbbVie: C; ARVO: S; Brightfocus Foundation: S; Genentech: S; Ivantis: C; NIH: S; Research to Prevent Blindness: S; Topcon: C.
Dr. Rizzo NYU: P.
Dr. Sunness Acuta: C; Apellis: US; Bluebird Bio: C; Consultantsis: C; Discern Health: C; GLG: C; Guidepoint Global: C; Lineage: C; LSC: C; ReVision Therapeutics: C.
Dr. Liu None.
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