Real-world outcomes of PK/PD-guided individualized emicizumab dose reduction in Chinese pediatric patients with hemophilia A: A prospective observational study

Abstract Background Emicizumab has markedly improved bleed prevention in hemophilia A, but its high cost remains a challenge, especially in resource-constrained settings. Many regions are now exploring dose reduction strategies to alleviate financial burden. However, empirical dose minimization without clear guidance may risk inadequate hemostatic protection and breakthrough bleeding. While standard weight-based dosing ensures efficacy, a personalized, pharmacokinetic/pharmacodynamic (PK/PD)-guided dosing strategy may reduce treatment burden without compromising bleed protection. Evidence supporting such individualized approaches in real-world remains limited. Objective This study aimed to evaluate the feasibility, safety, and preliminary effectiveness of PK/PD-guided emicizumab dose reduction in Chinese pediatric patients with hemophilia A, following an initial period of standard prophylaxis. Methods This was a prospective, single-center observational study conducted in a real-world clinical setting. Children under 18 years of age with severe congenital hemophilia A, either with or without FVIII inhibitors, who had received standard emicizumab prophylaxis for at least 12 months, were enrolled. After this observation period, patients and their caregivers were offered the option to transition to a reduced dosing regimen guided by individualized PK and PD targets. Emicizumab concentrations were measured using a modified one-stage clotting assay, and FVIII-equivalent activity was assessed using a chromogenic assay (HYPHEN). Individual pharmacokinetic parameters were estimated based on the population PK model by Retout et al. (Clin Pharmacokinet. 2020). The dose adjustment aimed to maintain FVIII-equivalent activity between 10–15 IU/dL and emicizumab trough concentrations above 30 μg/mL (±10 μg/mL). Patients were prospectively followed for a minimum of 6 months after dose reduction, with systematic monitoring for bleeding events, thrombotic complications, and treatment-related adverse events. Results A total of 46 patients were enrolled in the study. Among them, 15 patients transitioned to the PK/PD-guided Individualized dose reduction strategy after completing 12 months of standard emicizumab therapy. The median age of this subgroup was 2.0 years, with a range from 0.9 to 16.3 years. Of the 15 patients, 13 were negative for FVIII inhibitors, 2 had a history of inhibitors. The median monthly emicizumab dose was reduced from 5.4 mg/kg (range: 3.2–6.2) to 3.2 mg/kg (range: 2.6–4.0). Correspondingly, the median trough concentration decreased from 48.5 μg/mL (range: 36.5–68.7) to 32.1 μg/mL (range: 27.0–38.4). Despite the dose reduction, FVIII-equivalent activity remained within the target range in most patients, with a median of 12.3 IU/dL (range: 12.0–18.5). Throughout the 6-month follow-up under reduced dosing, no bleeding events, thrombotic complications, or treatment-related adverse events were observed. In addition, joint ultrasound assessments performed before and after dose adjustment showed no evidence of new or progressive damage, suggesting preserved joint health throughout the reduced dosing period. Conclusion This prospective real-world study demonstrates that emicizumab dose reduction guided by PK/PD targets is feasible, safe, and effective in pediatric patients with hemophilia A after an initial period of standard prophylaxis. The individualized approach maintained excellent bleed protection while substantially reducing drug exposure. These findings highlight the potential of PK/PD-guided dosing to improve access and cost-efficiency of emicizumab in settings where treatment affordability is a concern. Larger-scale, multi-center studies with extended follow-up are needed to confirm these promising results and support broader adoption of this strategy.