From pharmacokinetic-guided FVIII prophylaxis to low-dose Emicizumab prophylaxis: a pilot study revealed a flush of hope

Limited studies investigated the low dose emicizumab prophylaxis, especially in patients switched from pharmacokinetic (PK)-guided FVIII prophylaxis. A retrospective study was conducted among inhibitor-free boys with severe hemophilia A (SHA). They received PK-guided FVIII prophylaxis for six months and then switched to low dose emicizumab regimen for one year. The patients' demographic data, PK profiles and clinical outcomes (annualized bleeding rates and zero bleeding proportions) were collected from six-month pre-switch to one-year post-switch. The target joints and direct cost of treatment were also calculated. Twenty boys with SHA were enrolled and the median age was 4.3 years (IQR 3.1-5.8). With a median dose and infusion frequency of 25.3 IU/kg and 3.5 infusions per week, their trough FVIII level is 3.5 IU/dL with range of 2.0-5.8 IU/dL. After their switch to emicizumab, the median dose was 3.5 mg/kg/month with range of 3.0-4.0 mg/kg/month. Significantly improved annualized bleeding rate [0(0, 0.75) vs. 2(2,4), P < 0.0001], annualized treated bleeding rate [0(0, 0.75) vs. 1.0 (0, 3.5), P < 0.01], annualized joint bleeding rate [0(0,0) vs. 0(0, 3.5), P < 0.05] and zero bleeding proportion [75% vs. 20%, P < 0.01] were observed. Compared with FVIII, low dose emicizumab showed a much lower direct cost [median, 26676 vs. 35568 dollars yearly, P < 0.01]. Participants received well improved clinical outcomes of reduced annualized bleeding rates and increased zero bleeding proportions. The emicizumab prophylaxis demonstrated a significant decrease in direct cost of 25% compared with FVIII infusions. PK-guided individualized emicizumab prophylaxis could be expected to enhance cost-effectiveness further.