OBJECTIVES: We studied the potential for new extended-half-life recombinant factor IX (rFIX) treatments to reduce the burden of injections and to prevent bleeding. We indirectly compared annualized bleed rates (ABRs) and factor consumption (FC) during prophylaxis and the FC and number of injections to treat a bleed with rFIX Fc fusion protein (rFIXFc) and conventional rFIX products based on estimates from published literature. METHODS: A systematic review identified studies of routine prophylaxis in previously treated adults and adolescents with severe haemophilia B for comparison with rFIXFc (Powell 2013; Arm 1, weekly prophylaxis). Comparisons were based on simple differences between studies in median weekly FC and mean ABRs during prophylaxis, and the median FC and numbers of injections per bleed. Median weekly FC during prophylaxis was reported or estimated from the reported dose and weekly number of injections; FC per bleed was estimated from the reported dose and number of injections per bleed. The number of injections per bleed was calculated from the reported breakdown of bleeds by required number of injections or total number of injections divided by total bleeds. RESULTS: Three conventional rFIX studies were included: Roth 2001 and Lambert 2007 (BeneFIX®) and Windyga 2014 (Rixubis®). During prophylaxis, the mean ABR was comparable or lower and FC was lower with rFIXFc compared with rFIX (weighted average ABR with rFIX=4.0 vs. 3.1 with rFIXFc; weighted average increase in median weekly FC with rFIX=108%). The number of injections and FC per bleed were also lower with rFIXFc (weighted average number of injections with conventional rFIX=1.5 vs. 1.1 with rFIXFc; weighted average increase in median FC per bleed with rFIX=49%). CONCLUSIONS: Indirect comparisons of published study results suggest that, compared with conventional rFIX, rFIXFc may require reduced FC for prophylaxis and bleed treatment while maintaining similar bleeding rates for patients receiving prophylaxis.