Ranibizumab vs. aflibercept for wet age-related macular degeneration: network meta-analysis to understand the value of reduced frequency dosing

OBJECTIVE: Although a reduced aflibercept (2.0mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare the efficacy and safety of reduced frequency dosing for aflibercept, relative to other approved and marketed vascular endothelial growth factor inhibitors for wet AMD, over 12 months.

RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed according to a pre-specified protocol, a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard NMA models were used to analyze change at 3 months, and fractional polynomial regression over 12 months. Safety data were analyzed using binomial models with a logistic link function.

RESULTS: Five trials formed a complete evidence network. At three months, all posologies of aflibercept and ranibizumab resulted in similar changes in BCVA. Over 12 months, approved posologies of aflibercept and ranibizumab resulted in similar changes from baseline (between 6.7 (95% credible interval [CrI], 5.5, 7.8) to 9.1 (8.1, 10.1) ETDRS letters); however, reduced frequency aflibercept was associated with a smaller change (1.8 letters, [-25.9, 29.2]). There was a trend towards a greater change in BCVA, with increasing frequency of dosing. All posologies performed similarly with respect to safety, and CrIs were wide.

CONCLUSIONS: Approved posologies of ranibizumab and aflibercept are similarly effective treatments for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.