Klukowska Anna, Sidonio Robert F, Young Guy, Mancuso Maria Elisa, Álvarez-Román María Teresa, Bhatnagar Neha, Jansen Martina, Knaub Sigurd
Haemostasis Group of the Polish Society of Haematology and Transfusiology, 14 Indira Gandhi Street, Warsaw 02-776, Poland.
Hemophilia of Georgia Center for Bleeding and Clotting Disorders, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, USA.
Ther Adv Hematol. 2024 May 9;15:20406207241245511. doi: 10.1177/20406207241245511. eCollection 2024.
People with severe hemophilia A usually experience their first bleed early in life. In children with severe hemophilia A, primary prophylaxis is recommended to prevent recurrent and potentially life-threatening bleeds that significantly impact day-to-day life. Factor VIII (FVIII) prophylaxis is well-established in children and has been shown to reduce the development of hemophilic arthropathy. However, a major challenge of FVIII therapy is the development of neutralizing anti-FVIII antibodies (FVIII inhibitors). Simoctocog alfa (Nuwiq) is a human cell line-derived recombinant FVIII (rFVIII) whose immunogenicity, efficacy, and safety have been studied in 167 children with severe hemophilia A across two prospective clinical trials and their long-term extensions. In 105 previously untreated children, the inhibitor rate of 16.2% for high-titer inhibitors (26.7% for all inhibitors) was lower than published rates for hamster cell line-derived rFVIII products. There was no inhibitor development in previously untreated children with non-null mutations and in previously treated children. In a case series of 10 inhibitor patients, 8 (80%) underwent successful immune tolerance induction with simoctocog alfa with a median time to undetectable inhibitor of 3.5 months. In an analysis of 96 children who enrolled in the extension studies and received long-term simoctocog alfa prophylaxis for up to 5 years, median spontaneous, joint, and total annualized bleeding rates were 0.3, 0.4, and 1.8, respectively. No thromboembolisms were reported in any of the 167 children, and there were no treatment-related deaths. Optimal care of children should consider several factors, including minimization of inhibitor development risk, maintaining tolerance to FVIII, highly effective bleed prevention and treatment, safety, and impact on long-term outcomes such as bone and joint health. In this context we review the pediatric clinical data and ongoing studies with simoctocog alfa.
重度甲型血友病患者通常在幼年时首次出血。对于重度甲型血友病患儿，建议进行初级预防，以防止反复发生且可能危及生命的出血，这些出血会对日常生活产生重大影响。凝血因子VIII（FVIII）预防措施在儿童中已得到充分确立，并已证明可减少血友病性关节病的发生。然而，FVIII治疗的一个主要挑战是产生中和性抗FVIII抗体（FVIII抑制剂）。西莫考格α（Nuwiq）是一种源自人细胞系的重组FVIII（rFVIII），其免疫原性、疗效和安全性已在两项前瞻性临床试验及其长期扩展研究中对167例重度甲型血友病患儿进行了研究。在105例先前未接受治疗的儿童中，高滴度抑制剂的抑制剂发生率为16.2%（所有抑制剂的发生率为26.7%），低于仓鼠细胞系衍生的rFVIII产品的已发表发生率。在先前未接受治疗的非无效突变儿童和先前接受治疗的儿童中未出现抑制剂。在一个包含10例抑制剂患者的病例系列中，8例（80%）通过西莫考格α成功诱导免疫耐受，抑制剂检测不到的中位时间为3.5个月。在对96例参加扩展研究并接受长达5年的长期西莫考格α预防治疗的儿童进行的分析中，自发性、关节和年化总出血率中位数分别为0.3、0.4和1.8。167例儿童中均未报告血栓栓塞事件，也没有与治疗相关的死亡。儿童的最佳护理应考虑多个因素，包括将抑制剂产生风险降至最低、维持对FVIII的耐受性、高效预防和治疗出血、安全性以及对骨骼和关节健康等长期结局的影响。在此背景下，我们回顾了西莫考格α的儿科临床数据和正在进行的研究。
