Richmond, R.

Abstract Intracranial hemorrhage (ICH) and resulting neurologic disability are severe complications for a subset of infants with severe hemophilia A (HA). Although prophylactic factor replacement reduces bleeding risk, it is typically delayed until after age 1 year due to risks associated with central venous access placement. Emicizumab, a subcutaneous activated factor VIII (FVIII) mimetic, has demonstrated safety and efficacy in preventing ICH in infants aged <12 months in the HAVEN 7 trial. Despite its high cost, the cost-effectiveness of emicizumab prophylaxis initiated during the first year of life for infants with severe HA is not known. We developed a Markov cohort model to compare emicizumab prophylaxis to standard care (no prophylaxis) in infants aged 0 to 1 year with severe HA without FVIII inhibitors. The analysis was conducted from a US societal perspective over a lifetime horizon across all accepted willingness-to-pay (WTP) thresholds. The primary outcome was the incremental cost-effectiveness ratio (ICER) in US dollar per quality-adjusted life-year (QALY). Emicizumab prophylaxis and standard care accrued 25.6 and 25.1 QALYs at costs of $13.12 million and $13.07 million, respectively, resulting in an ICER of $99 900 per QALY (95% credible interval [CI], 84 000-120 000). Scenario analysis examining prophylaxis with low-dose emicizumab resulted in an ICER of $19 600 per QALY (95% CI, 12 000-29 000). Probabilistic sensitivity analyses showed that standard-dose emicizumab is the cost-effective strategy in 100%, 66%, and 0% of 10 000 Monte Carlo iterations at WTP thresholds of $150 000, $104 000, and $50 000 per QALY, respectively, and in 100% across all WTP thresholds for low-dose emicizumab.