Kingfisher study: Safety and efficacy of brolucizumab for DME
This was a 52-week, double-masked, phase 3 randomized clinical trial in which treatment-naive adults and adults who had previously received anti-VEGF therapy for DME were included.
Image credit: ©Wasim Alnahlawi – stock.adobe.com
The Kingfisher Study (NCT03917472) found that the visual outcomes after 1 year of brolucizumab, 6 mg, (Beovu, Novartis) in participants with diabetic macular edema (DME) did not differ significantly from those obtained with aflibercept (Eylea, Regeneron), although some superior anatomic improvements were seen with brolucizumab compared with aflibercept,1 according to Rishi P. Singh, MD, lead study author. He is from the Cleveland Clinic Martin Hospitals, Cleveland Clinic Florida, Stuart.
The investigators pointed out that while anti–vascular endothelial growth factor (VEGF) agents have improved visual outcomes for patients with DME compared with the results obtained with laser photocoagulation, the previous standard of care, studies have suggested that some patients may need frequent dosing that can be as often as every 4 weeks, to improve and maintain their functional and anatomic outcomes.
Kingfisher study design
This was a 52-week, double-masked, phase 3 randomized clinical trial in which treatment-naive adults and adults who had previously received anti-VEGF therapy for DME were included.
Patients were treated with intravitreal injections of either brolucizumab, 6 mg, every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks.
The primary endpoint was the change in the best-corrected visual acuity (BCVA) at week 52 compared with the baseline level. The secondary endpoints were the proportion of participants with a 2-step improvement or greater from baseline in the Diabetic Retinopathy Severity Scale (DRSS) score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, the change from baseline in the central subfield thickness (CST), and safety at week 52, Dr. Singh recounted.
Study results
A total of 517 participants (57.8% male; mean age 60.7 years) were included; 346 patients were randomized to brolucizumab and 171 patients to aflibercept.
The analysis showed that brolucizumab was noninferior to aflibercept in the change in the BCVA best-corrected visual acuity from baseline at week 52, with brolucizumab, showing a 12.2-letter improvement and aflibercept a 11.0-letter improvement (P < 0.001 for noninferiority)
More eyes treated with brolucizumab had no subretinal and intraretinal fluid compared with aflibercept. (brolucizumab, 41.6% versus aflibercept, 22.2%, a difference that reached significance (P <0 .001).
Treatment with brolucizumab also resulted in a greater change from baseline in the mean CST compared with aflibercept at week 52 (brolucizumab, −237.8 μm versus aflibercept, −196.5 μm), a difference that reached significance (P <0 .001).
The incidence rates of intraocular inflammation were 4.0% in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, those of retinal vasculitis 0.9% and 0.6%, respectively, and those retinal vascular occlusion 0.3% and 0.6%, respectively. One participant in the brolucizumab arm had retinal artery occlusion.
The investigators summarized, “In patients with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms, but some superior anatomic improvements were noted in the brolucizumab arm with a safety profile that appeared similar to previous brolucizumab trials.
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
