Brolucizumab shows favorable benefit-risk profile in DME
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Two phase 3 trials, KESTREL and KITE, identified brolucizumab as a viable diabetic macular edema treatment option, according to a study published in the American Journal of Ophthalmology.
“Brolucizumab 6 mg showed robust visual gains and anatomical improvements with an overall favorable benefit/risk profile in patients with DME,” David M. BrownMD, of Retina Consultants of Texas in Houston, and colleagues wrote.
Both studies were double-masked, multicenter trials that included adults with central-involved DME, HbA1c of 10% or less, best corrected visual acuity scores between approximately 20/32 and 20/320 Snellen, and central subfield thickness of at least 320 µm, according to the study.
Participants were randomized to receive brolucizumab 3 mg or 6 mg or aflibercept 2 mg in the KESTREL study (n = 566), and brolucizumab 6 mg or aflibercept 2 mg in the KITE study (n = 360). Those in the brolucizumab groups received five loading doses every 6 weeks, following by dosing every 12 weeks, while those in the aflibercept groups received five doses every 4 weeks, followed by fixed 8-week dosing.
Outcomes of interest included mean BCVA change at week 52, the number of participants maintained on 12-week dosing, change in Diabetic Retinopathy Severity Scale score, and incidence of ocular and non-ocular adverse events.
To evaluate the efficacy of treatments, researchers assessed BCVA, anatomical markers, color fundus photography and vascular leakage, with trial results showing visual gains associated with the brolucizumab treatment.
“The studies met their primary objective and demonstrated noninferiority of brolucizumab 6 mg to aflibercept 2 mg for the primary endpoint of change from baseline in BCVA at week 52 for the study eye, with a noninferiority margin of four letters (P < .001),” Brown and colleagues wrote.
Brolucizumab noninferiority also was met for the secondary week 40 to week 52 endpoint of change in BCVA, and anatomical outcomes were “favored” over aflibercept, according to the study.
“With its better fluid resolution, brolucizumab should therefore help to achieve one of the main aims of anti-VEGF therapy, which is to reliably resolve retinal fluid as early and as far as possible for optimal visual outcomes in patients with DME,” the authors wrote.
The proportion of patients with central subfield thickness of less than 280 µm was higher in both the brolucizumab 3 mg and 6 mg arms compared with the aflibercept arms between weeks 32 and 52 in both KESTREL and KITE studies.
Brolucizumab also had a well-tolerated safety profile, “although the overall risk of [intraocular inflammation], retinal vasculitis and retinal vascular occlusion were higher in brolucizumab-treated eyes compared with aflibercept-treated eyes,” the authors wrote.
They added, “[B]rolucizumab could provide an additional therapeutic option in DME that reduces the burden on patients, physicians and the health care system.”
Perspective
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DME has become one of the leading causes of vision loss in the adult working population. Current anti-VEGF treatments have replaced focal and grid laser photocoagulation; however, some patients continue to have persistent DME despite regular therapy. This can present a high medical burden to patients, which leads to noncompliance and decreased visual improvement.
Brolucizumab is FDA-approved to treat neovascular age-related macular degeneration and demonstrated comparable BCVA and anatomical outcomes compared to aflibercept. In both the KESTREL and KITE studies, brolucizumab demonstrated noninferiority with extended dosing intervals compared to aflibercept. This is a promising outcome, as patients have similar visual acuity and anatomical outcomes with fewer intravitreal injections.
The FDA has recently approved brolucizumab for treatment of DME but did reiterate warnings of retinal vasculitis and retinal vascular occlusion, especially in eyes with ocular inflammation. Thus, this treatment option is likely best for patients who need another treatment option or working adults who experience medical burden with frequent visits. However, close monitoring for these serious adverse events and exercising caution with its use in patients with higher risk for these complications is essential.
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