The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A

Expert Opinion on Drug Metabolism and Toxicology

Volumn 12, Issue 11, 2016, Pages 1313-1321

  McEneny King, Alanna ^a   Iorio, Alfonso ^b   Foster, Gary ^b   Edginton, Andrea N ^a  

^a UNIVERSITY OF WATERLOO   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

Author keywords

Dose individualization; factor VIII; haemophilia A; population pharmacokinetics

Indexed keywords

BLOOD CLOTTING FACTOR 8; BLOOD CLOTTING FACTOR 8 CONCENTRATE; RECOMBINANT BLOOD CLOTTING FACTOR 8; VON WILLEBRAND FACTOR;

AGE; BIOEQUIVALENCE; BLOOD GROUP; BODY WEIGHT; COST EFFECTIVENESS ANALYSIS; DRUG CLEARANCE; DRUG DOSE INDIVIDUALIZATION; DRUG DOSE REGIMEN; DRUG HALF LIFE; HEMOPHILIA A; HUMAN; PHARMACOKINETICS; POPULATION RESEARCH; PROPHYLAXIS; REVIEW; TREATMENT OUTCOME; VOLUME OF DISTRIBUTION AT STEADY-STATE;

EID: 84992741171     PISSN: 17425255     EISSN: 17447607     Source Type: Journal    
DOI: 10.1080/17425255.2016.1214711     Document Type: Review

References (96)

1. P.M.Mannucci, E.G.Tuddenham The hemophilias–from royal genes to gene therapy. N Engl J Med. 2001;344:1773–1779.
2. J.S.Stonebraker, P.H.Bolton-Maggs, J.M.Soucie, et al. A study of variations in the reported haemophilia A prevalence around the world. Haemophilia. 2010;16:20–32.
3. H.E.Castro, M.F.Briceno, C.P.Casas, et al. The history and evolution of the clinical effectiveness of haemophilia type a treatment:a systematic review. Indian J Hematol Blood Transfus. 2014;30:1–11.
4. I.M.Nilsson, U.Hedner, A.Ahlberg. Haemophilia prophylaxis in Sweden. Acta Paediatr Scand. 1976;65:129–135.
5. P.M.Mannucci. AIDS, hepatitis and hemophilia in the 1980s:memoirs from an insider. J Thromb Haemost. 2003;1:2065–2069.
6. J.M.Lusher, S.Arkin, C.F.Abildgaard, et al. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate Previously Untreated Patient Study Group. N Engl J Med. 1993;328:453–459.
7. R.S.Schwartz, C.F.Abildgaard, L.M.Aledort, et al. Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. N Engl J Med. 1990;323:1800–1805.
8. I.M.Nilsson, M.Blomback, O.Ramgren. Haemophilia in Sweden. VI. Treatment of haemophilia A with the human antihaemophilic factor preparation (fraction I–0). Acta Med Scand Suppl. 1962;379:61–110.
9. A.Ahlberg. Haemophilia in Sweden. VII. Incidence, treatment and prophylaxis of arthropathy and other musculo-skeletal manifestations of haemophilia A and B. Acta Orthop Scand Suppl. 1965;36:3–132.
10. I.E.Den Uijl, E.P.Mauser Bunschoten, G.Roosendaal, et al. Clinical severity of haemophilia A:does the classification of the 1950s still stand? Haemophilia. 2011;17:849–853.
11. J.Oldenburg. Prophylaxis in bleeding disorders. Thromb Res. 2011;127(Suppl 1):S14–S17.
12. E.Berntorp, G.Spotts, L.Patrone, et al. Advancing personalized care in hemophilia A:ten years’ experience with an advanced category antihemophilic factor prepared using a plasma/albumin-free method. Biologics. 2014;8:115–127.
13. K.Fischer, P.W.Collins, M.C.Ozelo, et al. When and how to start prophylaxis in boys with severe hemophilia without inhibitors:communication from the SSC of the ISTH. J Thromb Haemost. 2016;14:1105–1109. Accepted Article. doi:10.1111/jth.13298.
14. P.Petrini. Identifying and overcoming barriers to prophylaxis in the management of haemophilia. Haemophilia. 2007;13(Suppl 2):16–22.
15. M.Carcao, A.Srivastava. Factor VIII/factor IX prophylaxis for severe hemophilia. Semin Hematol. 2016;53:3–9.
16. M.J.Manco-Johnson, T.C.Abshire, A.D.Shapiro, et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med. 2007;357:535–544.
17. M.C.Ar, I.Vaide, E.Berntorp, et al. Methods for individualising factor VIII dosing in prophylaxis. Eur J Haematol Suppl. 2014;76:16–20.
18. S.Bjorkman, E.Berntorp. Pharmacokinetics of coagulation factors:clinical relevance for patients with haemophilia. Clin Pharmacokinet. 2001;40:815–832.
19. S.Bjorkman, A.Folkesson, S.Jonsson. Pharmacokinetics and dose requirements of factor VIII over the age range 3-74 years:a population analysis based on 50 patients with long-term prophylactic treatment for haemophilia A. Eur J Clin Pharmacol. 2009;65:989–998.
20. S.Bjorkman, M.Oh, G.Spotts, et al. Population pharmacokinetics of recombinant factor VIII:the relationships of pharmacokinetics to age and body weight. Blood. 2012;119:612–618.
21. M.Morfini. Comparative pharmacokinetic studies in haemophilia. Haemophilia. 2002;8(Suppl 2):30–33.
22. J.Wakefield. The Bayesian analysis of population pharmacokinetic models. J Am Stat Assoc. 1996;91:62–75.
23. P.W.Collins, S.Bjorkman, K.Fischer, et al. Factor VIII requirement to maintain a target plasma level in the prophylactic treatment of severe hemophilia A:influences of variance in pharmacokinetics and treatment regimens. J Thromb Haemost. 2010;8:269–275.
24. E.Samara, R.Granneman. Role of population pharmacokinetics in drug development:a pharmaceutical industry perspective. Clin Pharmacokinet. 1997;32:294–312.
25. E.I.Ette, P.J.Williams. Population pharmacokinetics I:background, concepts, and models. Ann Pharmacother. 2004;38:1702–1706.
26. N.H.Holford, T.Buclin. Safe and effective variability-a criterion for dose individualization. Ther Drug Monit. 2012;34:565–568.• This article describes the principles of dose individualization in greater detail, including how different levels of variability affect dosing decisions.
27. L.B.Sheiner, S.Beal, B.Rosenberg, et al. Forecasting individual pharmacokinetics. Clin Pharmacol Ther. 1979;26:294–305.
28. M.M.Tod, C.Padoin, O.Petitjean. Individualising aminoglycoside dosage regimens after therapeutic drug monitoring:simple or complex pharmacokinetic methods? Clin Pharmacokinet. 2001;40:803–814.
29. L.S.Ting, E.Villeneuve, M.H.Ensom. Beyond cyclosporine:a systematic review of limited sampling strategies for other immunosuppressants. Ther Drug Monit. 2006;28:419–430.
30. S.Bjorkman. Limited blood sampling for pharmacokinetic dose tailoring of FVIII in the prophylactic treatment of haemophilia A. Haemophilia. 2010;16:597–605.• This article demonstrates the feasibility of individualizing FVIII doses using only a few blood samples, and highlights the shortcomings of weight-based dosing strategies.
31. S.Bjorkman, M.Carlsson. The pharmacokinetics of factor VIII and factor IX:methodology, pitfalls and applications. Haemophilia. 1997;3:1–8.•• This article provides a review of FVIII (and FIX) pharmacokinetic studies up to the year 1994.
32. G.M.Brenner, C.W.Stevens. Pharmacokinetics. In:Pharmacology. 4th ed. Philadelphia (PA):Elsevier Saunders; 2013. p. 10.
33. S.R.Deitcher, J.Tuller, J.A.Johnson. Intranasal DDAVP induced increases in plasma von Willebrand factor alter the pharmacokinetics of high-purity factor VIII concentrates in severe haemophilia A patients. Haemophilia. 1999;5:88–95.
34. C.A.Lee, D.Owens, G.Bray, et al. Pharmacokinetics of recombinant factor VIII (recombinate) using one-stage clotting and chromogenic factor VIII assay. Thromb Haemost. 1999;82:1644–1647.
35. A.Saez, N.Bosh, N.Boadas, et al. Pharmacokinetics and acute tolerance of a double virus inactivated plasma derived factor VIII concentrate. Haemophilia. 1999;5:260–265.
36. T.C.Abshire, H.H.Brackmann, I.Scharrer, et al. Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy–International Kogenate-FS Study Group. Thromb Haemost. 2000;83:811–816.
37. J.S.Powell, M.Bush, J.Harrison, et al. Safety and efficacy of solvent/detergent-treated antihaemophilic factor with an added 80 degrees C terminal dry heat treatment in patients with haemophilia A. Haemophilia. 2000;6:140–149.
38. S.G.Courter, C.L.Bedrosian. Clinical evaluation of B-domain deleted recombinant factor VIII in previously treated patients. Semin Hematol. 2001;38:44–51.
39. C.Rothschild, I.Scharrer, H.H.Brackmann, et al. European data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patients. Haemophilia. 2002;8(Suppl 2):10–14.
40. J.M.Lusher, C.A.Lee, C.M.Kessler, et al. The safety and efficacy of B-domain deleted recombinant factor VIII concentrate in patients with severe haemophilia A. Haemophilia. 2003;9:38–49.
41. M.Morfini, S.Cinotti, A.Bellatreccia, et al. A multicenter pharmacokinetic study of the B-domain deleted recombinant factor VIII concentrate using different assays and standards. J Thromb Haemost. 2003;1:2283–2289.
42. V.Blanchette, A.D.Shapiro, R.Liesner, et al. Characterization of the pharmacokinetics of rFVIII in young pre-school children with Hemophilia, including an analysis of the influence of age and body weight. Blood (ASH Annual Meeting Abstracts). 2004;104:3084.
43. M.D.Tarantino, P.W.Collins, C.R.Hay, et al. Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method:pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10:428–437.
44. D.M.Wolf, R.Rokicka-Milewska, S.Lopaciuk, et al. Clinical efficacy, safety and pharmacokinetic properties of the factor VIII concentrate Haemoctin SDH in previously treated patients with severe haemophilia A. Haemophilia. 2004;10:438–448.
45. C.M.Kessler, J.C.Gill, G.C.White2nd, et al. B-domain deleted recombinant factor VIII preparations are bioequivalent to a monoclonal antibody purified plasma-derived factor VIII concentrate:a randomized, three-way crossover study. Haemophilia. 2005;11:84–91.
46. J.Di Paola, M.P.Smith, R.Klamroth, et al. ReFacto and advate:a single-dose, randomized, two-period crossover pharmacokinetics study in subjects with haemophilia A. Haemophilia. 2007;13:124–130.
47. J.S.Powell, D.J.Nugent, J.A.Harrison, et al. Safety and pharmacokinetics of a recombinant factor VIII with pegylated liposomes in severe hemophilia A. J Thromb Haemost. 2008;6:277–283.
48. M.Recht, L.Nemes, M.Matysiak, et al. Clinical evaluation of moroctocog alfa (AF-CC), a new generation of B-domain deleted recombinant factor VIII (BDDrFVIII) for treatment of haemophilia A:demonstration of safety, efficacy, and pharmacokinetic equivalence to full-length recombinant factor VIII. Haemophilia. 2009;15:869–880.
49. C.Santoro, A.Iorio, F.Ferrante, et al. Performance of recalibrated ReFacto laboratory standard in the measurement of FVIII plasma concentration via the chromogenic and one-stage assays after infusion of recalibrated ReFacto (B-domain deleted recombinant factor VIII). Haemophilia. 2009;15:779–787.
50. M.El-Ekiaby, H.A.Goubran, M.Radosevich, et al. Pharmacokinetic study of minipooled solvent/detergent-filtered cryoprecipitate factor VIII. Haemophilia. 2011;17:e884–e888.
51. U.Martinowitz, J.Bjerre, B.Brand, et al. Bioequivalence between two serum-free recombinant factor VIII preparations (N8 and ADVATE(R))–an open-label, sequential dosing pharmacokinetic study in patients with severe haemophilia A. Haemophilia. 2011;17:854–859.
52. L.A.Valentino, V.Mamonov, A.Hellmann, et al. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012;10:359–367.
53. V.Jimenez-Yuste, S.Lejniece, R.Klamroth, et al. The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight(R)), in patients with hemophilia A. J Thromb Haemost. 2015;13:370–379.
54. J.S.Powell, N.C.Josephson, D.Quon, et al. Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients. Blood. 2012;119:3031–3037.
55. T.E.Coyle, M.T.Reding, J.C.Lin, et al. Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A. J Thromb Haemost. 2014;12:488–496.
56. J.Mahlangu, J.S.Powell, M.V.Ragni, et al. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood. 2014;123:317–325.
57. A.Tiede, B.Brand, R.Fischer, et al. Enhancing the pharmacokinetic properties of recombinant factor VIII:first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost. 2013;11:670–678.
58. G.Young, J.Mahlangu, R.Kulkarni, et al. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015;13:967–977.
59. S.Bjorkman, V.S.Blanchette, K.Fischer, et al. Comparative pharmacokinetics of plasma- and albumin-free recombinant factor VIII in children and adults:the influence of blood sampling schedule on observed age-related differences and implications for dose tailoring. J Thromb Haemost. 2010;8:730–736.
60. A.J.Vlot, E.P.Mauser-Bunschoten, A.G.Zarkova, et al. The half-life of infused factor VIII is shorter in hemophiliac patients with blood group O than in those with blood group A. Thromb Haemost. 2000;83:65–69.
61. K.Fischer, R.Pendu, C.J.van Schooten, et al. Models for prediction of factor VIII half-life in severe haemophiliacs:distinct approaches for blood group O and non-O patients. PLoS One. 2009;4:e6745.
62. S.Kepa, B.Horvath, S.Reitter-Pfoertner, et al. Parameters influencing FVIII pharmacokinetics in patients with severe and moderate haemophilia A. Haemophilia. 2015;21:343–350.
63. M.Franchini, F.Capra, G.Targher, et al. Relationship between ABO blood group and von Willebrand factor levels:from biology to clinical implications. Thromb J. 2007;5:14,9560-5-14.
64. K.Fijnvandraat, M.Peters, J.W.ten Cate. Inter-individual variation in half-life of infused recombinant factor VIII is related to pre-infusion von Willebrand factor antigen levels. Br J Haematol. 1995;91:474–476.
65. H.C.Hazendonk, J.Lock, R.A.Mathot, et al. Perioperative treatment of hemophilia A patients:blood group O patients are at risk of bleeding complications. J Thromb Haemost. 2015;14:468–478.
66. S.Albanez, K.Ogiwara, A.Michels, et al. Aging and ABO blood type influence VWF and FVIII levels through interrelated mechanisms. J Thromb Haemost. 2016;14:953–963.
67. H.J.Weiss, I.I.Sussman, L.W.Hoyer. Stabilization of factor VIII in plasma by the von Willebrand factor. Studies on posttransfusion and dissociated factor VIII and in patients with von Willebrand’s disease. J Clin Invest. 1977;60:390–404.
68. B.A.Konkle. Von Willebrand factor and aging. Semin Thromb Hemost. 2014;40:640–644.
69. S.Henrard, N.Speybroeck, C.Hermans. Impact of being underweight or overweight on factor VIII dosing in hemophilia A patients. Haematologica. 2013;98:1481–1486.
70. R.Kawai, M.Lemaire, J.L.Steimer, et al. Physiologically based pharmacokinetic study on a cyclosporin derivative, SDZ IMM 125. J Pharmacokinet Biopharm. 1994;22:327–365.
71. S.Kitchen, I.Jennings, M.Makris, et al. Factor VIII assay variability in postinfusion samples containing full length and B-domain deleted FVIII. Haemophilia. 2016. doi:10.1111/hae.12962. [Epub ahead of print]
72. R.A.Gruppo, D.Brown, M.M.Wilkes, et al. Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis–a meta-analysis. Haemophilia. 2003;9:251–260.
73. W.Kreuz, C.E.Ettingshausen, A.Zyschka, et al. Inhibitor development in previously untreated patients with hemophilia A:a prospective long-term follow-up comparing plasma-derived and recombinant products. Semin Thromb Hemost. 2002;28:285–290.
74. S.C.Gouw, J.G.van der Bom, G.Auerswald, et al. Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A:the CANAL cohort study. Blood. 2007;109:4693–4697.
75. A.Iorio, S.Halimeh, S.Holzhauer, et al. Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates:a systematic review. J Thromb Haemost. 2010;8:1256–1265.
76. J.F.Harrison, A.L.Bloom, C.F.Abildgaard. The pharmacokinetics of recombinant factor VIII. The rFactor VIII clinical trial group. Semin Hematol. 1991;28:29,35; discussion 36.
77. M.Morfini, E.Marchesini, E.Paladino, et al. Pharmacokinetics of plasma-derived vs. recombinant FVIII concentrates:a comparative study. Haemophilia. 2015;21:204–209.
78. M.R.Steele, K.Nagel, A.K.Chan. Pharmacokinetics of recombinant and plasma-derived factor VIII products in paediatric patients with severe haemophilia A. Haemophilia. 2014;20:e100–e101.
79. L.A.George, R.M.Camire. Profile of efraloctocog alfa and its potential in the treatment of hemophilia A. J Blood Med. 2015;6:131–141.
80. I.A.Ivens, A.Baumann, T.A.McDonald, et al. PEGylated therapeutic proteins for haemophilia treatment:a review for haemophilia caregivers. Haemophilia. 2013;19:11–20.
81. A.Opar. The clot thickens for long-lasting drugs that stop hemophilia short. Nat Med. 2013;19:121.
82. R.T.Peters, G.Toby, Q.Lu, et al. Biochemical and functional characterization of a recombinant monomeric factor VIII-Fc fusion protein. J Thromb Haemost. 2013;11:132–141.
83. A.Skotnicki, T.J.Lissitchkov, V.Mamonov, et al. Efficacy, safety and pharmacokinetic profiles of a plasma-derived VWF/FVIII concentrate (VONCENTO(R)) in subjects with haemophilia A (SWIFT-HA study). Thromb Res. 2016;137:119–125.
84. S.Schulte. Innovative coagulation factors:albumin fusion technology and recombinant single-chain factor VIII. Thromb Res. 2013;131(Suppl 2):S2–S6.
85. S.Zollner, E.Raquet, P.Claar, et al. Non-clinical pharmacokinetics and pharmacodynamics of rVIII-SingleChain, a novel recombinant single-chain factor VIII. Thromb Res. 2014;134:125–131.
86. S.Neelakantan, S.Li, J.Powell, et al. Population pharmacokinetic analysis of long-lasting recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A. J Thromb Haemost. 2013;11:354. Abstract PA 2.06-3.
87. A.H.Miners, C.A.Lee. Setting research priorities to improve cost-effectiveness estimations of primary prophylaxis with clotting factor for people with severe haemophilia. Haemophilia. 2004;10(Suppl 1):58–62.
88. A.Miners. Revisiting the cost-effectiveness of primary prophylaxis with clotting factor for the treatment of severe haemophilia A. Haemophilia. 2009;15:881–887.
89. K.A.Johnson, Z.Y.Zhou. Costs of care in hemophilia and possible implications of health care reform. Hematology Am Soc Hematol Educ Program. 2011;2011:413–418.
90. A.Gringeri, M.Wolfsegger, K.N.Steinitz, et al. Recombinant full-length factor VIII (FVIII) and extended half-life FVIII products in prophylaxis–new insight provided by pharmacokinetic modelling. Haemophilia. 2015;21:300–306.
91. A.D.Shapiro, M.V.Ragni, R.Kulkarni, et al. Recombinant factor VIII Fc fusion protein:extended-interval dosing maintains low bleeding rates and correlates with von Willebrand factor levels. J Thromb Haemost. 2014;12:1788–1800.
92. E.Berntorp. Pharmacokinetics of plasma-derived and recombinant factor IX:using population pharmacokinetics with sparse sampling data needs further study. Haemophilia. 2013;19:805–807.
93. S.Fernandes, M.Carvalho, M.Lopes, et al. Impact of an individualized prophylaxis approach on young adults with severe hemophilia. Semin Thromb Hemost. 2014;40:785–789.
94. G.R.Jayandharan, A.Srivastava. The phenotypic heterogeneity of severe hemophilia. Semin Thromb Hemost. 2008;34:128–141.
95. J.Oldenburg. Optimal treatment strategies for hemophilia:achievements and limitations of current prophylactic regimens. Blood. 2015;125:2038–2044.• This article provides an excellent review of the current prophylactic regimens, and highlights how individualized dosing strategies can improve patient outcomes and resource use.
96. C.L.Kempton, G.C.White2nd. How we treat a hemophilia A patient with a factor VIII inhibitor. Blood. 2009;113:11–17.