Post hoc analysis compares brolucizumab and aflibercept for diabetic macular edema

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Ophthalmology. Retina Published April 14, 2026 Medically reviewed April 25, 2026 Study authors: Ip Michael, Chaudhary Varun, He Fanyin, Bouillaud Emmanuel, Kim Yongsoo, Igwe Franklin, Singer Micha… PubMed ↗ DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Interpret post hoc brolucizumab anatomical advantages cautiously; prospective confirmation needed.

This post hoc analysis of a randomized controlled trial evaluated 517 participants with diabetic macular edema, stratified by prior anti-VEGF treatment status (370 treatment-naive, 147 prior-treated). Participants received intravitreal brolucizumab 6 mg or aflibercept 2 mg, with outcomes assessed at 52 weeks.

In the prior-treated subgroup, mean BCVA improvement was +11.0 letters with brolucizumab versus +8.6 letters with aflibercept. In the treatment-naive subgroup, improvements were +12.6 and +12.2 letters, respectively. Central subfield thickness reductions were greater with brolucizumab in both subgroups (prior-treated: -255.3 µm vs -189.6 µm; treatment-naive: -231.4 µm vs -199.0 µm). A higher proportion of brolucizumab-treated participants achieved a fluid-free macula at week 52. DRSS score improvements trended higher with brolucizumab.

Safety data showed the incidence of intraocular inflammation-related adverse events in the prior-treated subgroup was 4.2% with brolucizumab and 5.8% with aflibercept. In the treatment-naive subgroup, incidence was 4.0% with brolucizumab and 1.7% with aflibercept. Serious adverse events and discontinuation rates were not reported.

The primary limitation is the exploratory, post hoc nature of the analysis, which was not prespecified. Statistical comparisons between treatments were not provided. The study was proprietary. For clinical practice, these findings suggest brolucizumab may offer anatomical advantages in fluid resolution, but the evidence is hypothesis-generating. Decisions should be based on prospective trial data and individual risk-benefit assessment, particularly regarding IOI risk.

Study Details

Study typeRct

Sample sizen = 251

EvidenceLevel 2

PublishedApr 2026

PMID41130413

View Original Abstract ↓

OBJECTIVE: To evaluate visual and anatomical outcomes of brolucizumab 6 mg versus aflibercept 2 mg in subgroups of participants with/without prior anti-VEGF treatment for diabetic macular edema in the KINGFISHER study. DESIGN: Post hoc analysis of the KINGFISHER study. PARTICIPANTS: Of 517 participants randomized, 370 (71.6%) were treatment-naive (brolucizumab 6 mg [n = 251]; aflibercept 2 mg [n = 119]), and 147 (28.4%) prior-treated (brolucizumab 6 mg [n = 95]; aflibercept 2 mg [n = 52]) participants were included. METHODS: Visual and anatomical outcomes were analyzed, and descriptive statistics were provided for outcome measures. MAIN OUTCOME MEASURES: Assessment of the changes (least squares mean [standard error]) from baseline to week 52 in best-corrected visual acuity (BCVA) and central subfield thickness, proportion of study eyes with absence of both subretinal fluid and intraretinal fluid at week 52, proportion of participants with ≥2-step improvement from baseline to week 52 in Diabetic Retinopathy Severity Scale (DRSS) score, and incidence of intraocular inflammation (IOI)-related adverse events. RESULTS: The mean BCVA changes from baseline to week 52 in the prior-treated and treatment-naive subgroups were brolucizumab 6 mg (+11.0 [1.00] letters) versus aflibercept 2 mg (+8.6 [1.35] letters) and brolucizumab 6 mg (+12.6 [0.58] letters) versus aflibercept 2 mg (+12.2 [0.85] letters), respectively. Central subfield thickness reductions from baseline to week 52 in the prior-treated subgroup were brolucizumab 6 mg (-255.3 [11.27] μm) versus aflibercept 2 mg (-189.6 [15.32] μm) and in the treatment-naive subgroup were brolucizumab 6 mg (-231.4 [5.65] μm) versus aflibercept 2 mg (-199.0 [8.21] μm). A higher proportion of participants treated with brolucizumab 6 mg had a fluid-free macula at week 52 in both subgroups. The proportion of participants with ≥2-step improvement from baseline in DRSS at week 52 was comparable between the 2 subgroups and trended higher in the brolucizumab 6 mg arm. The incidence of IOI was brolucizumab 6 mg (4.2%) versus aflibercept 2 mg (5.8%) in the prior-treated subgroup and was brolucizumab 6 mg (4.0%) versus aflibercept 2 mg (1.7%) in the treatment-naive subgroup. CONCLUSIONS: These results demonstrate the effectiveness of brolucizumab 6 mg irrespective of the prior treatment status of the participants. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.