Comparing the efficacy of bevacizumab to ranibizumab in patients with diabetic macular edema: the BRDME study

Abstract

Purpose : Bevacizumab is widely used off-label as an alternative for the registered and more expensive anti-vascular endothelial growth factor (VEGF) agent ranibizumab in the treatment of diabetic macular edema (DME). We conducted a prospective, double-masked, randomized clinical trial to generate conclusive evidence on the non-inferiority of intravitreal bevacizumab compared to ranibizumab in patients with diabetic macular edema (Trialregister.nl NTR3247).

Methods : From June 2012 till February 2018, in 8 Dutch clinical centers, 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n=86) or 0.5 mg ranibizumab (n=84). Patients over 18 years of age, diagnosed with type 1 or type 2 Diabetes Mellitus, a glycosylated haemoglobin (HbA1c) of <12%, central area thickness on optical coherence tomography (OCT) of >325 microns and visual impairment due to DME with best corrected visual acuity (BCVA) of ≥ 24 letters and < 79 letters, were eligible for participation. Primary outcome was the change in BCVA from baseline to month 6 compared between both treatment arms, with a non-inferiority margin of 3.5 letters.

Results : Performing covariance analysis, the estimated difference in BCVA between treatment arms was 1.8 in favor of ranibizumab, with the lower bound of the one-sided 95% confidence interval of -3.6 letters, thereby exceeding the non-inferiority margin of 3.5 letters. The mean (± standard deviation) BCVA improved from baseline to 6 months with 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group, P = 0.094. Participants with an initial worse BCVA at baseline (≤68 letters, approximately ≤20/50) improved with 7.2±7.3 letters after 6 months when receiving bevacizumab and with 10.9±10.4 letters when receiving ranibizumab, however this difference was not significant (P = 0.109). Participants with an initial better BCVA at baseline (≥69 letters, approximately ≥20/40) improved with 3.4±5.8 letters in the bevacizumab group and with 4.1±6.1 letters in the ranibizumab group, P = 0.483.

Conclusions : This study shows that, based on the change in BCVA from baseline to month 6, inferiority of bevacizumab to ranibizumab could not be rejected. In addition, patients with a lower BCVA at baseline showed a trend for a better outcome with ranibizumab. Our study confirms the differential efficacy of anti-VEGF agents in the treatment of DME.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.