Abstract
Background Emicizumab, a bispecific monoclonal antibody that mimics activated FVIII, is now the standard prophylaxis for hemophilia A. However, real-world pharmacokinetic (PK) and pharmacodynamic (PD) data in Chinese pediatric populations remain limited. Ethnic and developmental factors—such as body size, nutritional status, and earlier treatment initiation—may influence drug exposure and clinical response.
Objective To characterize the PK/PD profiles and real-world bleeding outcomes of emicizumab in Chinese children with hemophilia A.
Methods This retrospective study was conducted at Beijing Children's Hospital from December 2023 to July 2025. Peripheral blood samples were collected during both the loading and maintenance phases. Emicizumab concentrations were measured using a modified one-stage assay, and FVIII-equivalent activity was assessed with a chromogenic FVIII assay (HYPHEN). Age, height, weight, BMI, albumin, and bleeding events were recorded. PK parameters were estimated using the published population pharmacokinetic model developed by Retout et al. (Clin Pharmacokinet. 2020;59(12):1611–1625), without re-fitting to the current dataset.
Results A total of 46 pediatric patients were enrolled, including 39 (84.8%) with severe hemophilia A. Among them, 15 were previously untreated or minimally treated patients (PUPs/MTPs), and 9 had a history of inhibitors. The median age at enrollment was 3.52 years (range: 0.93-16.25), and the median age at emicizumab initiation was 1.40 years. The median height was 92.0 cm (range: 67.0-175.0 cm), weight 14.5 kg (range: 8.5-41.8 kg), BMI 16.8 kg/m² (range: 13.8-21.5 kg/m²), and albumin 46.1 g/L (41.4-49.6 g/L).
During the loading phase (n = 40), patients received a median dose of 2.85 mg/kg per week (range: 2.14–3.90 mg/kg). The corresponding emicizumab concentration had a median of 57.7 μg/mL (range: 31.8–79.9 μg/mL), and FVIII-equivalent activity a median of 14.6 IU/dL (range: 7.4–39.2 IU/dL). Only one trauma-related treated bleeding episode occurred during this period.
During the maintenance phase (n = 43), the median dose was 5.21 mg/kg every 28 days (range: 2.54–6.46 mg/kg), with a median emicizumab concentration of 50.6 μg/mL (range: 17.3–81.7 μg/mL) and FVIII-equivalent activity of 20.2 IU/dL (range: 8.9–39.6 IU/dL). Six trauma-related bleeds were observed, and the median annualized bleeding rate (ABR) was 0.
Emicizumab concentration correlated positively with FVIII-equivalent activity, both by linear regression (Y = 0.9569·X + 33.24, R² = 0.37, p < 0.01) and Spearman correlation (ρ = 0.56, p < 0.01).
Estimated PK parameters were as follows (median [range]): CL/F: 0.0637 L/day [0.0421–0.1578]; V/F: 2.1543 L [1.2629–6.2103]; t½: 23.44 days [20.79–27.28]; and kₑ: 0.0296 day⁻¹ [0.0254–0.0333].
Conclusion This first real-world PK/PD study of emicizumab in Chinese pediatric patients demonstrates high exposure, predictable pharmacokinetics, and excellent bleeding control. The findings support early initiation, individualized dosing, and population-specific monitoring strategies in pediatric hemophilia A care.
