Brolucizumab as Effective as Aflibercept in Macular Edema Treatment

There were no clinically meaningful differences in visual outcomes when patients with diabetic macular edema (DME) were treated with either brolucizumab or aflibercept, according to a study published in JAMA Ophthalmology. Anatomic improvements were found in patients who had received brolucizumab.

DME is a common complication of patients with diabetes that can be treated with anti–vascular endothelial growth factor (VEGF) agents. Previous studies have shown that frequent dosing may be required for the best treatment. Brolucizumab was found to result in vision gains in 2 studies where treatment was dosed every 12 and 8 weeks. The current study, KINGFISHER, aimed to perform a head-to-head comparison of brolucizumab 6 mg to aflibercept 2 mg, both dosed every 4 weeks.

The study was a phase 3 randomized clinical trial that spanned 52 weeks and was conducted in 115 sites in Hungary, Israel, Slovakia, and the United States. The study aimed to assess the efficacy and safety of brolucizumab in patients with type 1 or 2 diabetes with visual impairment caused by DME. Patients could have received previous treatment or could be treatment naïve as long as they did not receive anti-VEGF treatment in the 3 months before the start of the study. Patients were excluded if they had a stroke or a myocardial infarction in the 6 months before baseline, ocular disorders that could confound results, uncontrolled glaucoma, or active intraocular or periocular infection.

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Patients were split into 2 groups: brolucizumab 6 mg every 4 weeks (n = 311) and aflibercept 2 mg every 4 weeks (n = 156). The patients were stratified based on their best-corrected visual acuity (BCVA) at baseline. The change in BCVA from baseline to week 52 was the primary end point of the analysis.

A total of 57.8% of all participants were male, and the mean (SD) age of the participants was 60.7 (10.2) years. The majority of the participants (84.1%) were White, with 10.8% identifying as Black, 4.1% as Asian, 0.8% as unknown race, 0.4% as American Indian, and 0.2% as Native Hawaiian or Pacific Islander. The participants in the brolucizumab group were more often female and older than 65 years.

Both groups saw an improvement in BCVA at week 52 compared with baseline. Brolucizumab demonstrated noninferiority to aflibercept at week 52, with patients using brolucizumab having a mean estimated 12.2 letter score increase compared with an 11.0 letter score increase in the aflibercept group (difference, 1.1; 95% CI, –0.6 to 2.9).

The estimated proportions of patients who had a gain of 5 or more, 10 or more, and 15 or more in letter score from baseline to week 52 or had achieved a BCVA of 84 or more in letter score were higher by 9.3% (95% CI, 1.7%-17.0%), 7.7% (95% CI, –1.5% to 17.0%), and 5.5% (95% CI, –2.7% to 14.3%), respectively, in the brolucizumab group compared with the aflibercept group.

The probability for the absence of DME in a patient at week 52 was higher in brolucizumab (86.6%; 95% CI, 30.2%-98.3%) compared with aflibercept (51.6%; 95% CI, 35.7%-65.4%). Brolucizumab also had a higher possibility of reaching first absence of DME (2.1-fold; 95% CI, 1.6-2.7).

Adverse events (AEs) were comparable between both groups. The most common AEs were vitreous detachment, punctate keratitis, cataracts, and conjunctival hemorrhage; there were no nonocular AEs or deaths associated with treatment. AEs of special interest were more common in patients who took brolucizumab compared with aflibercept (4.3% vs 3.5%).

There were some limitations to this study. The interval between brolucizumab doses used in this study is not approved by the FDA and doses should be taken every 8 weeks at the most frequent.

The researchers concluded that brolucizumab had some superior anatomic improvements in patients who took the medication but that aflibercept and brolucizumab had similar visual outcomes. The safety profile was in line with previous studies on brolucizumab.

Reference

Singh RP, Barakat MR, Ip MS, et al. Efficacy and safety of brolucizumab for diabetic macular edema: the KINGFISHER randomized clinical trial. JAMA Ophthalmol. Published online November 16, 2023. doi:10.1001/jamaophthalmol.2023.5248