Plasma and albumin-free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients

被引:128
|
作者
Blanchette, V. S. [1 ]
Shapiro, A. D. [2 ]
Liesner, R. J. [3 ]
Navarro, F. Hernandez [4 ]
Warrier, I. [5 ]
Schroth, P. C. [6 ]
Spotts, G. [6 ]
Ewenstein, B. M. [6 ]
机构
[1] Univ Toronto, Hosp Sick Children, Div Hematol Oncol, Toronto, ON M5G 1X8, Canada
[2] Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA
[3] Great Ormond St Hosp Sick Children, London WC1N 3JH, England
[4] Hosp Univ La Paz, Serv Hematol, Madrid, Spain
[5] Childrens Hosp Michigan, Detroit, MI 48201 USA
[6] Baxter BioSci, Westlake Village, CA USA
关键词
factor VIII; hemophilia A; pediatrics; pharmacokinetics; rAHF-PFM; safety;
D O I
10.1111/j.1538-7836.2008.03032.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: The pharmacokinetics of factor VIII replacement therapy in preschool previously treated patients (PTPs) with hemophilia A have not been well characterized. Objectives: To assess the pharmacokinetics, efficacy and safety of a plasma-free recombinant FVIII concentrate, ADVATE [Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method, rAHF-PFM], in children < 6 years of age with severe hemophilia. Patients/methods: Fifty-two boys, one girl, mean (+/- SD) age 3.1 +/- 1.5 years and >= 50 days of prior FVIII exposure, were enrolled in a prospective study of ADVATE rAHF-PFM at 23 centers. Results: The mean terminal phase half-life (t(1/2)) was 9.88 +/- 1.89 h, and the mean adjusted in vivo recovery (IVR) was 1.90 +/- 0.43 IU dL(-1) (IU kg(-1))(-1). Over the 1-6-year age range, t(1/2) of rAHF-PFM increased by 0.40 h year(-1). IVR increased by 0.095IU dL(-1)(IU kg(-1))(-1) (kg m(-2))(-1) in relation to body mass index (BMI). Patients primarily received prophylaxis. Median (range) annual joint bleeds were 0.0 (0.0-5.8), 0.0 (0.0-6.1) and 14.2 (0.0-34.5) for standard prophylaxis, modified prophylaxis and on-demand treatment, respectively. Bleeds were managed in 90% (319/354) of episodes with one or two rAHF-PFM infusions; response was rated excellent/good in 93.8% of episodes. Over a median 156 exposure days, no FVIII inhibitors were detected and no related severe adverse events or unusual non-serious adverse events were seen. Conclusions: Children < 6 years of age appear to have shorter FVIII t(1/2) and lower IVR values than older subjects. However, these parameters increased with age (t(1/2)) and BMI (adjusted IVR), respectively. rAHF-PFM was clinically effective and well tolerated, with no signs of increased immunogenicity in previously treated young children with hemophilia A.
引用
收藏
页码:1319 / 1326
页数:8
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