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

Victor S. Blanchette, A. D. Shapiro, R. J. Liesner, F. Hernández Navarro, I. Warrier, P. C. Schroth, G. Spotts, B. M. Ewenstein, T. Abshire, A. Angiolillo, S. Arkin, D. Becton, A. Thompson, D. DiMichele, J. DiPaola, K. Hoots, M. Kurth, C. Manno, I. Ortiz, S. PipeM. Recht, F. Shafer, M. Tarantino, W. Y. Wong, C. Male, M. Siimes, T. Lambert, C. Rothschild, H. Chambost, C. Negrier, E. Fressinaud, H. Brackmann, W. Kreuz, H. Pollmann, G. Auerswald, A. Gringeri, M. van den Berg, C. Altisent, F. Hernandez, P. Petrini, P. Collins

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

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 (t1/2) was 9.88 ± 1.89h, 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, t1/2 of rAHF-PFM increased by 0.40 h year-1. IVR increased by 0.095 IU 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 t1/2 and lower IVR values than older subjects. However, these parameters increased with age (t1/2) 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.

Original languageEnglish (US)
Pages (from-to)1319-1326
Number of pages8
JournalJournal of Thrombosis and Haemostasis
Volume6
Issue number8
DOIs
StatePublished - Aug 1 2008

Keywords

  • Factor VIII
  • Hemophilia A
  • Pediatrics
  • Pharmacokinetics
  • Safety
  • rAHF-PFM

ASJC Scopus subject areas

  • Hematology

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    Blanchette, V. S., Shapiro, A. D., Liesner, R. J., Navarro, F. H., Warrier, I., Schroth, P. C., Spotts, G., Ewenstein, B. M., Abshire, T., Angiolillo, A., Arkin, S., Becton, D., Thompson, A., DiMichele, D., DiPaola, J., Hoots, K., Kurth, M., Manno, C., Ortiz, I., ... Collins, P. (2008). Plasma and albumin-free recombinant factor VIII: Pharmacokinetics, efficacy and safety in previously treated pediatric patients. Journal of Thrombosis and Haemostasis, 6(8), 1319-1326. https://doi.org/10.1111/j.1538-7836.2008.03032.x