Background No head-to-head clinical trials have been published comparing aflibercept and bevacizumab for the neovascular form of age-related macular degeneration (AMD). Adjusted indirect comparisons may provide useful information on the relative efficacy of competing interventions.

Purpose To compare the efficacy of aflibercept and bevacizumab for the treatment of wet AMD using an adjusted indirect comparison.

Materials and methods PubMed was searched for randomised controlled trials (RCTs) comparing aflibercept or bevacizumab with ranibizumab. Selection criteria were: 1) phase III RCTs; 2) intravitreal aflibercept 2.0 mg (every two months after three consecutive monthly doses) versus monthly intravitreal ranibizumab 0.5 mg; 3) monthly intravitreal ranibizumab 0.50 mg versus monthly intravitreal bevacizumab 1.25 mg; 4) patients included with active choroidal neovascularisation secondary to AMD and 5) similar duration and methodology.

A meta-analysis of RTCs comparing aflibercept versus ranibizumab and bevacizumab versus ranibizumab was performed. Odds ratios and 95% confidence intervals for dichotomous data were calculated by Mantel-Haenszel’s method. An adjusted indirect comparison by Bucher’s method using the ITC software from Canadian Agency for Drug Technologies in Health was done, with ranibizumab as a common comparator. The endpoint was the proportion of patients who improved by ≥15 ETDRs letters at 52 weeks.

Results Two RCTs comparing aflibercept with ranibizumab (VIEW-1 and VIEW-2) and two RTCs comparing bevacizumab versus ranibizumab (CATT-1 and CATT-2) met the inclusion criteria. Meta-analysis showed no significant difference between aflibercept and ranibizumab (ARR:1.50% [-3.79 to 6.73]) or bevacizumab and ranibizumab (ARR: 20% [-9.0 to 4.0]). The adjusted indirect comparison didn’t show a statistically significant difference between aflibercept and bevacizumab (ARR: 3.0% [-4.90 to 10.90]).

Conclusions Notwithstanding the limitations of an adjusted indirect comparison, no significant differences were found between aflibercept and bevacizumab in AMD. Until head-to head trials are available, adjusted indirect comparisons based on trial data could be relevant to guide therapeutic choices.

No conflict of interest.