Ljung Rolf, Chan Anthony K C, Ahuja Sanjay P, Mancuso Maria Elisa, Marquez Jose Francisco Cabre, Volk Florian, Blanchette Victor, Kerlin Bryce A, Trakymiene Sonata Saulyte, Glosli Heidi, Kenet Gili
Department of Clinical Sciences Lund-Pediatrics, Lund University, Lund, Sweden.
McMaster Children's Hospital, McMaster University, Hamilton, Ontario, Canada.
Eur J Haematol. 2025 Mar;114(3):556-565. doi: 10.1111/ejh.14362. Epub 2024 Dec 12.
To report the long-term safety and efficacy of BAY 81-8973 in the LEOPOLD Kids extension phase.
Patients received BAY 81-8973 (25-50 IU/kg) at least twice weekly. The primary endpoint was safety, assessed in all patients who entered the extension phase (n = 82). Efficacy endpoints were assessed in patients without high-titre inhibitors/immune tolerance induction (n = 67).
Children (n = 82) received BAY 81-8973 for a median of 3.1 years per patient and a median of 405 exposure days per patient. Long-term BAY 81-8973 treatment was well tolerated, with no cases of de novo inhibitor development in the extension phase. Annualised bleeding rates (ABRs) within 48 h of prophylaxis were low for all bleeds (median [IQR], 0.7 [0-1.9]; mean, 1.4 [SD, 2.1]) and for joint bleeds (median [IQR], 0 [0-0.7]; mean, 0.5 [SD, 1.1]) (n = 67). Twenty-one of 67 patients (31.3%) had zero bleeds within 48 h of prophylaxis; the treatment response was 'good'/'excellent' in 87.9% of bleeds, and most bleeds resolved with ≤ 2 BAY 81-8973 infusions (83.5%).
Long-term BAY 81-8973 treatment is well tolerated and maintains low ABRs for all bleeds and joint bleeds in children with severe haemophilia A.
ClinicalTrials.gov identifier: NCT01311648.
报告BAY 81-8973在LEOPOLD Kids扩展阶段的长期安全性和有效性。
患者至少每周两次接受BAY 81-8973（25-50 IU/kg）治疗。主要终点为安全性，在所有进入扩展阶段的患者（n = 82）中进行评估。有效性终点在无高滴度抑制剂/免疫耐受诱导的患者（n = 67）中进行评估。
82名儿童接受BAY 81-8973治疗，每位患者的中位治疗时间为3.1年，每位患者的中位暴露天数为405天。长期BAY 81-8973治疗耐受性良好，扩展阶段无新发抑制剂病例。预防后48小时内的年化出血率（ABR）对于所有出血均较低（中位数[四分位间距]，0.7[0-1.9]；均值，1.4[标准差，2.1]），对于关节出血也较低（中位数[四分位间距]，0[0-0.7]；均值，0.5[标准差，1.1]）（n = 67）。67名患者中有21名（31.3%）在预防后48小时内无出血；87.9%的出血治疗反应为“良好”/“优秀”，大多数出血通过≤2次BAY 81-8973输注得以解决（83.5%）。
长期BAY 81-8973治疗耐受性良好，且在重度甲型血友病儿童中对所有出血和关节出血均维持较低的ABR。
ClinicalTrials.gov标识符：NCT01311648。
