Mullins E S, Stasyshyn O, Alvarez-Román M T, Osman D, Liesner R, Engl W, Sharkhawy M, Abbuehl B E
Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU, Lviv, Ukraine.
Haemophilia. 2017 Mar;23(2):238-246. doi: 10.1111/hae.13119. Epub 2016 Nov 27.
Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T ) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy.
To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A.
PTPs <12 years without history of FVIII inhibitors received twice-weekly infusions of 50 ± 10 IU kg BAX 855 for ≥50 exposure days. Prophylactic dose increases to ≤80 IU kg were allowed under predefined conditions. PK was evaluated after single infusions of 60 ± 5 IU kg .
T and mean residence time were extended 1.3- to 1.5-fold compared to ADVATE (n = 31), depending on the analysis used. The point estimate for the mean annualized bleeding rate in 66 subjects receiving a median of 1.9 weekly infusions of 51.3 IU kg of BAX 855 each was 3.04 (median 2.0); 1.10 (median 0) for joint and 1.16 (median 0) for spontaneous bleeds. Overall, 38% of subjects had zero bleeds. No bleeds were severe. Haemostatic efficacy was rated excellent or good for 90% of bleeds; 91% were treated with one or two infusions. In 8/14 subjects all target joints resolved. No subject developed FVIII inhibitors or persistent binding antibodies that affected safety or efficacy. No adverse reactions occurred.
Twice-weekly prophylaxis with BAX 855 was safe and efficacious in paediatric PTPs with severe haemophilia A.
原发性因子VIII（FVIII）预防治疗是重度A型血友病患儿的最佳治疗方法。预计他们将受益于延长半衰期（T）的FVIII覆盖，通过减少输注频率同时保持止血效果。
确定基于全长重组FVIII（ADVATE）的聚乙二醇（peg）化FVIII（BAX 855）在既往接受过治疗的重度A型血友病儿科患者（PTPs）中的免疫原性、药代动力学（PK）、疗效、安全性和生活质量。
年龄小于12岁且无FVIII抑制剂病史的PTPs，每周两次输注50±10 IU/kg的BAX 855，持续≥50个暴露日。在预定义条件下允许预防性剂量增加至≤80 IU/kg。单次输注60±5 IU/kg后评估PK。
根据所使用的分析方法，与ADVATE相比，T和平均驻留时间延长了1.3至1.5倍（n = 31）。66名受试者接受中位数为每周1.9次、每次51.3 IU/kg的BAX 855输注，其年化出血率的点估计值为3.04（中位数为2.0）；关节出血为1.10（中位数为0），自发性出血为1.16（中位数为0）。总体而言，38%的受试者无出血。无严重出血。90%的出血止血疗效被评为优秀或良好；91%的出血通过一或两次输注进行治疗。在14名受试者中的8名中，所有目标关节均恢复正常。没有受试者产生影响安全性或疗效的FVIII抑制剂或持续结合抗体。未发生不良反应。
对于重度A型血友病儿科PTPs，每周两次使用BAX 855进行预防治疗是安全有效的。
