Individualizing Factor Replacement Therapy in Severe Hemophilia

Manuel D. Carcao; Alfonso Iorio

doi:10.1055/s-0035-1552563

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2015; 41(08): 864-871
DOI: 10.1055/s-0035-1552563

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Individualizing Factor Replacement Therapy in Severe Hemophilia

Manuel D. Carcao

¹Division of Haematology/Oncology and Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

,

Alfonso Iorio

²Departments of Clinical Epidemiology and Biostatistics and Medicine, McMaster University, Hamilton, Ontario, Canada

› Author Affiliations

Abstract

Prophylactic replacement of factor concentrate is the established optimal treatment to avoid or minimize joint disease in severe hemophilia patients, thus ultimately improving their life expectancy and quality of life toward values matching those in the normal population. Where uncertainty still exists is around the optimal regimen to be prescribed for prophylaxis, and more and more treaters and patients are showing interest in patient tailored approaches to prophylaxis, aiming at matching the prophylaxis regimen to the specific needs of the patient. The rationale behind tailoring the prophylaxis regimen to the individual patient is based on the significant variability that exists between patients (all with the same label of severe hemophilia) with respect to their bleeding phenotype, their pharmacokinetic handling of factor, their levels of physical activity, and a variety of other characteristics that contribute to differential prophylaxis needs of patients. Of course, any form of tailoring of prophylaxis needs to take into consideration the economic resources of the country; for many countries very intense prophylaxis regimens are just not possible. This article will review different concerns and strategies when tailoring prophylaxis, and will address how these issues will apply to the new longer acting factor concentrates in development.

Keywords

hemophilia - prophylaxis - individualization - tailoring - personalized

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References

References
1 Manco-Johnson MJ, Abshire TC, Shapiro AD , et al. Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007; 357 (6) 535-544
2 Iorio A, Marchesini E, Marcucci M, Stobart K, Chan AK. Clotting factor concentrates given to prevent bleeding and bleeding-related complications in people with hemophilia A or B. Cochrane Database Syst Rev 2011; (9) CD003429
3 Gringeri A, Lundin B, von Mackensen S, Mantovani L, Mannucci PM ; ESPRIT Study Group. A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost 2011; 9 (4) 700-710
4 Valentino LA, Mamonov V, Hellmann A , et al; Prophylaxis Study Group. 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 (3) 359-367
5 Manco-Johnson MJ, Kempton CL, Reding MT , et al. Randomized, controlled, parallel-group trial of routine prophylaxis vs. on-demand treatment with sucrose-formulated recombinant factor VIII in adults with severe hemophilia A (SPINART). J Thromb Haemost 2013; 11 (6) 1119-1127
6 Collins PW, Blanchette VS, Fischer K , et al; rAHF-PFM Study Group. Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009; 7 (3) 413-420
7 Collins PW, Björkman S, Fischer K , 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 (2) 269-275
8 Björkman S, Ahlén V. Population pharmacokinetics of plasma-derived factor IX in adult patients with haemophilia B: implications for dosing in prophylaxis. Eur J Clin Pharmacol 2012; 68 (6) 969-977
9 Fischer K, Astermark J, van der Bom JG , et al. Prophylactic treatment for severe haemophilia: comparison of an intermediate-dose to a high-dose regimen. Haemophilia 2002; 8 (6) 753-760
10 Daliri AA, Haghparast H, Mamikhani J. Cost-effectiveness of prophylaxis against on-demand treatment in boys with severe hemophilia A in Iran. Int J Technol Assess Health Care 2009; 25 (4) 584-587
11 Wu R, Luke KH, Poon MC , et al. Low dose secondary prophylaxis reduces joint bleeding in severe and moderate haemophilic children: a pilot study in China. Haemophilia 2011; 17 (1) 70-74
12 Schimpf K, Fischer B, Rothmann P. Hemophilia A prophylaxis with factor VIII concentrate in a home-treatment program: a controlled study. Scand J Haematol Suppl 1977; 30: 79-80
13 Collins PW. Personalized prophylaxis. Haemophilia 2012; 18 (Suppl. 04) 131-135
14 Björkman S. Evaluation of the TCIWorks Bayesian computer program for estimation of individual pharmacokinetics of FVIII. Haemophilia 2011; 17 (1) e239-e240
15 Björkman S. Limited blood sampling for pharmacokinetic dose tailoring of FVIII in the prophylactic treatment of haemophilia A. Haemophilia 2010; 16 (4) 597-605
16 Carlsson M, Berntorp E, Björkman S, Lindvall K. Pharmacokinetic dosing in prophylactic treatment of hemophilia A. Eur J Haematol 1993; 51 (4) 247-252
17 van Dijk K, van der Bom JG, Lenting PJ , et al. Factor VIII half-life and clinical phenotype of severe hemophilia A. Haematologica 2005; 90 (4) 494-498
18 Björkman S, Folkesson A, Jönsson S. 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 (10) 989-998
19 Blanchette VS, Shapiro AD, Liesner RJ , et al; rAHF-PFM Clinical Study Group. Plasma and albumin-free recombinant factor VIII: pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost 2008; 6 (8) 1319-1326
20 Ljung R, Auerswald G, Benson G , et al. Novel coagulation factor concentrates: issues relating to their clinical implementation and pharmacokinetic assessment for optimal prophylaxis in haemophilia patients. Haemophilia 2013; 19 (4) 481-486
21 Konkle BA, Ebbesen LS, Erhardtsen E , et al. Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors. J Thromb Haemost 2007; 5 (9) 1904-1913
22 Carcao MD, van den Berg HM, Ljung R, Mancuso ME ; PedNet and the Rodin Study Group. Correlation between phenotype and genotype in a large unselected cohort of children with severe hemophilia A. Blood 2013; 121 (19) 3946-3952 , S1
23 Feldman BM, Pai M, Rivard GE , et al; Association of Hemophilia Clinic Directors of Canada Prophylaxis Study Group. Tailored prophylaxis in severe hemophilia A: interim results from the first 5 years of the Canadian Hemophilia Primary Prophylaxis Study. J Thromb Haemost 2006; 4 (6) 1228-1236
24 Risebrough N, Oh P, Blanchette V, Curtin J, Hitzler J, Feldman BM. Cost-utility analysis of Canadian tailored prophylaxis, primary prophylaxis and on-demand therapy in young children with severe haemophilia A. Haemophilia 2008; 14 (4) 743-752
25 Hacker MR, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia. Haemophilia 2001; 7 (4) 392-396
26 Lindvall K, Colstrup L, Wollter IM , et al. Compliance with treatment and understanding of own disease in patients with severe and moderate haemophilia. Haemophilia 2006; 12 (1) 47-51
27 Duncan N, Shapiro A, Ye X, Epstein J, Luo MP. Treatment patterns, health-related quality of life and adherence to prophylaxis among haemophilia A patients in the United States. Haemophilia 2012; 18 (5) 760-765
28 De Moerloose P, Urbancik W, Van Den Berg HM, Richards M. A survey of adherence to haemophilia therapy in six European countries: results and recommendations. Haemophilia 2008; 14 (5) 931-938
29 Rath T, Baker K, Dumont JA , et al. Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics. Crit Rev Biotechnol 2015; 35 (2) 235-254
30 Metzner HJ, Pipe SW, Weimer T, Schulte S. Extending the pharmacokinetic half-life of coagulation factors by fusion to recombinant albumin. Thromb Haemost 2013; 110 (5) 931-939
31 Pipe SW. The hope and reality of long-acting hemophilia products. Am J Hematol 2012; 87 (Suppl. 01) S33-S39
32 Powell JS, Pasi KJ, Ragni MV , et al; B-LONG Investigators. Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B. N Engl J Med 2013; 369 (24) 2313-2323
33 Mahlangu J, Powell JS, Ragni MV , et al; A-LONG Investigators. Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A. Blood 2014; 123 (3) 317-325
34 Broderick CR, Herbert RD, Latimer J , et al. Association between physical activity and risk of bleeding in children with hemophilia. JAMA 2012; 308 (14) 1452-1459