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, V. Blanchette, A. Thompson, D. DiMichele, J. DiPaola, K. Hoots, M. Kurth, C. Manno, I. Ortiz & 25 others S. Pipe, Michael Recht, F. Shafer, A. Shapiro, M. Tarantino, I. Warrier, 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, R. Liesner, P. Collins

Research output: Contribution to journalArticle

114 Citations (Scopus)

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 1/2) 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 1/2 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 2008
Externally publishedYes

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Factor VIII
Serum Albumin
Pharmacokinetics
Hemophilia A
Pediatrics
Safety
Body Mass Index
Joints
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Plasma and albumin-free recombinant factor VIII : Pharmacokinetics, efficacy and safety in previously treated pediatric patients. / Blanchette, Victor S.; Shapiro, A. D.; Liesner, R. J.; Navarro, F. Hernández; Warrier, I.; Schroth, P. C.; Spotts, G.; Ewenstein, B. M.; Abshire, T.; Angiolillo, A.; Arkin, S.; Becton, D.; Blanchette, V.; Thompson, A.; DiMichele, D.; DiPaola, J.; Hoots, K.; Kurth, M.; Manno, C.; Ortiz, I.; Pipe, S.; Recht, Michael; Shafer, F.; Shapiro, A.; Tarantino, M.; Warrier, I.; Wong, W. Y.; Male, C.; Siimes, M.; Lambert, T.; Rothschild, C.; Chambost, H.; Negrier, C.; Fressinaud, E.; Brackmann, H.; Kreuz, W.; Pollmann, H.; Auerswald, G.; Gringeri, A.; van den Berg, M.; Altisent, C.; Hernandez, F.; Petrini, P.; Liesner, R.; Collins, P.

In: Journal of Thrombosis and Haemostasis, Vol. 6, No. 8, 08.2008, p. 1319-1326.

Research output: Contribution to journalArticle

Blanchette, VS, Shapiro, AD, Liesner, RJ, Navarro, FH, Warrier, I, Schroth, PC, Spotts, G, Ewenstein, BM, Abshire, T, Angiolillo, A, Arkin, S, Becton, D, Blanchette, V, Thompson, A, DiMichele, D, DiPaola, J, Hoots, K, Kurth, M, Manno, C, Ortiz, I, Pipe, S, Recht, M, Shafer, F, Shapiro, A, Tarantino, M, Warrier, I, Wong, WY, Male, C, Siimes, M, Lambert, T, Rothschild, C, Chambost, H, Negrier, C, Fressinaud, E, Brackmann, H, Kreuz, W, Pollmann, H, Auerswald, G, Gringeri, A, van den Berg, M, Altisent, C, Hernandez, F, Petrini, P, Liesner, R & Collins, P 2008, 'Plasma and albumin-free recombinant factor VIII: Pharmacokinetics, efficacy and safety in previously treated pediatric patients', Journal of Thrombosis and Haemostasis, vol. 6, no. 8, pp. 1319-1326. https://doi.org/10.1111/j.1538-7836.2008.03032.x
Blanchette, Victor S. ; Shapiro, A. D. ; Liesner, R. J. ; Navarro, F. Hernández ; Warrier, I. ; Schroth, P. C. ; Spotts, G. ; Ewenstein, B. M. ; Abshire, T. ; Angiolillo, A. ; Arkin, S. ; Becton, D. ; Blanchette, V. ; Thompson, A. ; DiMichele, D. ; DiPaola, J. ; Hoots, K. ; Kurth, M. ; Manno, C. ; Ortiz, I. ; Pipe, S. ; Recht, Michael ; Shafer, F. ; Shapiro, A. ; Tarantino, M. ; Warrier, I. ; Wong, W. Y. ; Male, C. ; Siimes, M. ; Lambert, T. ; Rothschild, C. ; Chambost, H. ; Negrier, C. ; Fressinaud, E. ; Brackmann, H. ; Kreuz, W. ; Pollmann, H. ; Auerswald, G. ; Gringeri, A. ; van den Berg, M. ; Altisent, C. ; Hernandez, F. ; Petrini, P. ; Liesner, R. ; Collins, P. / Plasma and albumin-free recombinant factor VIII : Pharmacokinetics, efficacy and safety in previously treated pediatric patients. In: Journal of Thrombosis and Haemostasis. 2008 ; Vol. 6, No. 8. pp. 1319-1326.
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TY - JOUR

T1 - Plasma and albumin-free recombinant factor VIII

T2 - Pharmacokinetics, efficacy and safety in previously treated pediatric patients

AU - Blanchette, Victor S.

AU - Shapiro, A. D.

AU - Liesner, R. J.

AU - Navarro, F. Hernández

AU - Warrier, I.

AU - Schroth, P. C.

AU - Spotts, G.

AU - Ewenstein, B. M.

AU - Abshire, T.

AU - Angiolillo, A.

AU - Arkin, S.

AU - Becton, D.

AU - Blanchette, V.

AU - Thompson, A.

AU - DiMichele, D.

AU - DiPaola, J.

AU - Hoots, K.

AU - Kurth, M.

AU - Manno, C.

AU - Ortiz, I.

AU - Pipe, S.

AU - Recht, Michael

AU - Shafer, F.

AU - Shapiro, A.

AU - Tarantino, M.

AU - Warrier, I.

AU - Wong, W. Y.

AU - Male, C.

AU - Siimes, M.

AU - Lambert, T.

AU - Rothschild, C.

AU - Chambost, H.

AU - Negrier, C.

AU - Fressinaud, E.

AU - Brackmann, H.

AU - Kreuz, W.

AU - Pollmann, H.

AU - Auerswald, G.

AU - Gringeri, A.

AU - van den Berg, M.

AU - Altisent, C.

AU - Hernandez, F.

AU - Petrini, P.

AU - Liesner, R.

AU - Collins, P.

PY - 2008/8

Y1 - 2008/8

N2 - 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 1/2) 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 1/2 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.

AB - 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 1/2) 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 1/2 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.

KW - Factor VIII

KW - Hemophilia A

KW - Pediatrics

KW - Pharmacokinetics

KW - rAHF-PFM

KW - Safety

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JO - Journal of Thrombosis and Haemostasis

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