Abstract Background: Prophylactic treatment is essential for children with severe hemophilia A to prevent bleeding episodes and long-term joint damage. However, traditional factor VIII infusion therapy poses significant challenges in infants and young toddlers due to limited venous access. Emicizumab, a subcutaneous bispecific monoclonal antibody that mimics the function of factor VIII, provides a novel prophylactic approach that does not require intravenous administration, making it especially suitable for this population. Despite its promise, real-world data on the use of emicizumab in children under 3 years of age remain limited. Objective: To assess the real-world safety and efficacy of emicizumab prophylaxis in children under 3 years of age with severe hemophilia A and to summarize the dosing strategies and clinical outcomes observed at a single center in China. Methods: We conducted a retrospective review of all patients under 3 years of age with severe hemophilia A who initiated emicizumab prophylaxis at our institution between July 2020 and December 2024. Data collected included age at treatment initiation, prior factor VIII exposure days, inhibitor status, dosing regimens, follow-up duration, bleeding episodes, and adverse events. The median age at initiation was 10.3 months (range: 0.8–31 months), and the median number of prior exposure days to factor VIII was 15 (range: 1–150). Two patients had pre-existing inhibitors (one high-titer 336 BU and one low-titer 0.75 BU); six were inhibitor-negative, and three had not undergone inhibitor testing prior to prophylaxis initiation. Results: A total of 11 children met the inclusion criteria. Six infants (≤12 months) received loading doses of 3 mg/kg weekly for 4 weeks (n=5) or 6 mg/kg monthly (n=1, neonate), followed by maintenance dosing every two weeks. Five toddlers (≥1 year) received initial doses of 0.75 -2 mg/kg weekly for 4–5 weeks, then transitioned to maintenance regimens every 10–15 days. The median follow-up duration was 115 weeks (range: 35–263). Four patients experienced no bleeding episodes throughout the follow-up period. The remaining seven patients had only one or two breakthrough bleeds each, most of which were mild and trauma-related (e.g., injection site hematomas, bruises from minor falls). Two patients experienced spontaneous bleeds after approximately 12 months of continuous prophylaxis: one gastrointestinal hemorrhage in the infant receiving monthly dosing, and one ankle joint bleed in a toddler on a biweekly regimen. Both events resolved without complications and prophylaxis was maintained. One inhibitor-positive infant discontinued emicizumab after 50 weeks and subsequently suffered a spontaneous intracranial hemorrhage three months later. Prophylaxis was resumed following hemostatic control, with no further spontaneous bleeding. No new inhibitors were detected during the study period. Among eight patients with factor VIII-equivalent activity measurements, levels ranged from 17.5% to 47.5%. No thrombotic events, serious injection-site reactions, or other adverse events were observed. Conclusion: Emicizumab prophylaxis demonstrated excellent safety and efficacy in children under 3 years of age with severe hemophilia A. Most patients remained bleed-free or experienced only minor, trauma-associated bleeding events. The only serious spontaneous bleed occurred in a patient who had discontinued treatment, emphasizing the importance of strict adherence to the prophylactic regimen. These findings support the early use of emicizumab in infants and toddlers and reinforce the need to maintain continuous prophylaxis without unplanned interruptions to achieve optimal outcomes.
Hu et al. (Mon,) studied this question.
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