To assess efficacy and safety of brolucizumab versus aflibercept in patients with diabetic macular edema (DME).

We performed a systematic review and meta-analysis with trial sequential analysis (TSA). We searched Embase, Cochrane Central Register of Controlled Trials and PubMed databases from inception to February 16, 2024 for randomized controlled trials (RCTs) comparing brolucizumab with aflibercept in patients with DME and reporting any of the visual, anatomical and safety outcomes of interest. We conducted a TSA of safety outcomes to assess the risk of statistical errors.

1253 patients (1253 eyes) from 3 RCTs were included, of whom 57% received brolucizumab and 43% received aflibercept. Mean follow-up ranged from 52 to 100 weeks. Brolucizumab was non-inferior to aflibercept when comparing the mean change of best-corrected visual acuity from baseline (least squares mean difference [LSMD] 0.29; 95% confidence interval [CI] −1.37 to 1.95; p = 0.73). Change in central subfield thickness was significantly greater in the brolucizumab group compared with aflibercept (LSMD −24.5 μm; 95% CI −48.2 to −0.7 μm; p < 0.05). Incidence of adverse events of special interest (AESIs) (risk ratio [RR] 1.7; p = 0.08) and incidence of ≥1 ocular adverse events (AEs) (RR 0.95; p = 0.45) were not significantly different between groups.

Brolucizumab was non-inferior in functional outcomes and was superior to aflibercept in anatomical parameters. Ocular AEs and AESIs were numerically low and not statistically significant. Our findings underscore the importance of new RCTs powered to assess safety outcomes in order to suggest brolucizumab as an alternative to the treatment of DME.