Background. Emicizumab is a novel monoclonal antibody approved for the prevention and treatment of bleeds in patients with hemophilia A with or without inhibitors. The development of inhibitors, which are neutralizing antibodies to clotting factor replacement therapy, is a major treatment-related complication in hemophilia management. In patients with inhibitors, bleed prophylaxis using emicizumab has been shown to be cost-effective compared to prophylaxis using bypassing agents – with supporting evidence for its reimbursement in this population in Canada. However, in patients without inhibitors, the cost-effectiveness compared to standard bleed prophylaxis with clotting factor concentrates remains unknown.

Objective. To estimate the incremental cost per Quality-Adjusted Life-Years (QALYs) associated with emicizumab prophylaxis compared to clotting factor prophylaxis in patients without inhibitors from a Canadian public payer perspective.

Methods. A decision-analytic Markov model was developed in a population of non-inhibitor hemophilia A patients aged ≥36 years. Efficacy, safety, cost, and utility data for the 2 strategies (emicizumab and clotting factor prophylaxis) were obtained from Randomized-Controlled Trials (RCTs) and published epidemiological and cost literature. Expected costs and QALYs were derived using Monte Carlo simulations in a cycle length of 1 week over a lifetime horizon. Incremental cost-utility ratio (ICUR) was estimated with uncertainty evaluated by probabilistic sensitivity analysis and presented in Cost-Effectiveness Acceptability Curves (CEACs).

Results: Compared with clotting factor prophylaxis, emicizumab prophylaxis was less costly ($3,527,172) and more effective (0.9 QALY gained) over a lifetime horizon. In the probabilistic sensitivity analysis, emicizumab prophylaxis had a 100% probability of being cost-effective at any willingness-to-pay threshold.

Conclusion: In patients with hemophilia A without inhibitors, bleed prophylaxis using emicizumab is cost-effective compared to prophylaxis with clotting factor concentrates and should be considered for reimbursement in the Canadian hemophilia population.