Brolucizumab Versus Aflibercept for DME: One-Year RCT Outcomes

Journal Highlights

JAMA Ophthalmology, December 2023

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In the KINGFISHER randomized controlled trial (RCT), Singh et al. compared the efficacy and safety of brolucizumab and aflibercept in the treatment of diabetic macular edema (DME). The results at 52 weeks indicated no significant difference in VA between the two treatments. The proportion of eyes with retinal fluid at this point was significantly higher in the aflibercept arm. No new safety concerns were identified.

Participants of this multicenter, double-masked, phase 3 study were adults with type 1 or 2 diabetes and DME-related visual impairment. They were assigned randomly (2:1) to receive brolucizumab (6 mg every four weeks) or aflibercept (2 mg every four weeks). The main efficacy measure was the change in BCVA from baseline to week 52. Secondary end points included safety, fluid-free macula, improvement of >2 steps in the Diabetic Retinopathy Severity Scale (DRSS) score, and changes in central subfield thickness.

The mean age of the study group was 60.7 years; 57.8% were men. Overall, 346 patients received brolucizumab and 171 received aflibercept. BCVA findings (EDTRS letter score) from baseline to week 52 indicated that brolucizumab was not inferior to aflibercept. The letter score improved by 12.2 with brolucizumab and 11.0 with aflibercept (difference, 1.1; 95% CI, –0.6 to 2.9; noninferiority margin, 4; p < .001). The proportion of eyes without subretinal or intraretinal fluid was higher with brolucizumab (41.6% vs. 22.2%; difference, 20.0%; 95% CI, 12.5% to 28.6%; p < .001). The change in mean central subfield thickness by week 52 was −237.8 μm with brolucizumab and −196.5 μm with aflibercept (difference, –41.4; 95% CI, –58.9% to –23.8%; p < .001). The proportion of patients whose DRSS score rose by >2 steps was greater in the brolucizumab arm at week 12 (25.3% vs. 17.8%), week 24 (37.1% vs. 32.2%), and week 52 (43.0% vs. 38.1%).

Intraocular inflammation was more common with brolucizumab (4.0% vs. 2.9%), as was retinal vasculitis (0.9% vs. 0.6%). Retinal vascular occlusion was more common with aflibercept (0.6% vs. 0.3%). There was one retinal artery occlusion (brolucizumab arm).

Findings of this RCT suggest that brolucizumab may dry and stabilize the retina, said the authors, while maintain­ing VA. The potential to achieve dryness with fewer injections could translate to improved patient compliance and reduced health care costs. The authors noted that the dosing schedule for brolucizumab in this trial (every four weeks) is not approved by the FDA, nor is it stated in the product’s prescribing information, and that physicians need to consider the risk-benefit ratio.

The original article can be found here.