Institute of Experimental Hematology and Transfusion Medicine, Universitätsklinikum Bonn, Bonn, Germany.
Department of Pediatrics, Nara Medical University, Nara, Japan.
Pediatr Blood Cancer. 2020 Oct;67(10):e28474. doi: 10.1002/pbc.28474. Epub 2020 Aug 9.
Data regarding management of pediatric persons with hemophilia A (PwHA) with factor VIII (FVIII) inhibitors are limited. This prospective noninterventional study (NCT02476942) evaluated annualized bleeding rates (ABRs), safety, and health-related quality of life (HRQoL) in pediatric PwHA with FVIII inhibitors.
PwHA aged <12 years with current FVIII inhibitors and high-titer inhibitor history were enrolled. Participants remained on usual treatment; no interventions were applied. Outcomes included ABR, safety, and HRQoL.
Twenty-four PwHA aged 2-11 years (median 7.5) were enrolled and monitored for 8.7-44.1 weeks (median 23.4). In the episodic (n = 10) and prophylactic (n = 14) groups, respectively, 121 of 185 (65.4%) and 101 of 186 (54.3%) bleeds were treated using activated prothrombin complex concentrate (aPCC) and/or recombinant activated FVII (rFVIIa). ABRs (95% confidence interval) were 19.4 (13.2-28.4) and 18.5 (14.2-24.0) for treated bleeds, and 32.7 (20.5-52.2) and 33.1 (22.4-48.9) for all bleeds, respectively. Most prophylactic group participants (92.9%) were prescribed aPCC; 50% adhered to their prescribed treatment regimen. Adherence to prophylactic rFVIIa was not assessed. Serious adverse events included hemarthrosis (12.5%) and mouth hemorrhage (12.5%); the most common nonserious adverse event was viral upper respiratory tract infection (12.5%). HRQoL showed functional impairment at baseline; scores remained stable throughout, with little intergroup variation.
ABRs remained high in pediatric PwHA with inhibitors receiving standard treatment. This study demonstrates the need for more effective treatments, with reduced treatment burden, to prevent bleeds, increase prophylaxis adherence, and improve patient outcomes.
有关患有因子 VIII（FVIII）抑制剂的儿科血友病 A（PwHA）患者管理的数据有限。本项前瞻性非干预性研究（NCT02476942）评估了患有 FVIII 抑制剂的儿科 PwHA 的年化出血率（ABR）、安全性和健康相关生活质量（HRQoL）。
纳入了当前患有 FVIII 抑制剂且具有高滴度抑制剂病史的＜12 岁 PwHA。参与者继续接受常规治疗；未应用任何干预措施。研究结局包括 ABR、安全性和 HRQoL。
纳入了 24 名年龄为 2-11 岁（中位数为 7.5 岁）的 PwHA，并对其进行了 8.7-44.1 周（中位数为 23.4 周）的监测。在发作性（n=10）和预防性（n=14）组中，分别有 121/185（65.4%）和 101/186（54.3%）的出血接受了活化的凝血酶原复合物浓缩物（aPCC）和/或重组激活的 FVII（rFVIIa）治疗。治疗出血的 ABR（95%置信区间）分别为 19.4（13.2-28.4）和 18.5（14.2-24.0），所有出血的 ABR 分别为 32.7（20.5-52.2）和 33.1（22.4-48.9）。大多数预防性组参与者（92.9%）处方了 aPCC；50%的参与者遵守了其规定的治疗方案。未评估预防性 rFVIIa 的依从性。严重不良事件包括关节积血（12.5%）和口腔出血（12.5%）；最常见的非严重不良事件是病毒性上呼吸道感染（12.5%）。HRQoL 在基线时显示出功能障碍；整个研究过程中评分保持稳定，组间差异较小。
接受标准治疗的患有抑制剂的儿科 PwHA 的 ABR 仍然较高。本研究表明，需要更有效的治疗方法，减少治疗负担，以预防出血、提高预防治疗的依从性并改善患者结局。
