Comparing the efficacy of bevacizumab and ranibizumab in patients with diabetic macular edema: the BRDME study, a randomized trial

Abstract Purpose To generate conclusive evidence on the non-inferiority of intravitreal bevacizumab compared to ranibizumab in patients with diabetic macular edema (DME). Design Comparative, randomized, double-masked, multicenter, non-inferiority clinical trial. Participants Eligible patients were over 18 years of age, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin (HbA1c) 325 microns, and visual impairment from DME with a best corrected visual acuity (BCVA) of ≥24 letters and ≤78 letters. Methods From June 2012 to February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n=86) or 0.5 mg ranibizumab (n=84). Main Outcome Measures Primary outcome was change in BCVA from baseline to month 6 compared between the two treatment arms. The non-inferiority margin was 3.5 letters. Results The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months follow-up, BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the two-sided 90% confidence interval (CI) was -3.626 letters, exceeding the non-inferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared to bevacizumab (64.2±104.2 μm). In a post-hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared to bevacizumab. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms (lower bound of the two-sided 90% CI:-2.566 letters). Conclusions Based on change in BCVA from baseline to month 6, the non-inferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomical outcomes with ranibizumab. Our study confirms the potential differential efficacy of anti-vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities.