A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

Emel Aygören-Pürsün; Inge Scharrer; German Kogenate Study Group

doi:10.1055/s-0038-1665410

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1997; 78(05): 1352-1356
DOI: 10.1055/s-0038-1665410

Review Article

Schattauer GmbH Stuttgart

A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

Emel Aygören-Pürsün

The Center of Internal Medicine, University Hospital, Frankfurt, Germany

,

Inge Scharrer

The Center of Internal Medicine, University Hospital, Frankfurt, Germany

,

German Kogenate Study Group

› Author Affiliations

Abstract

PDF Download

Summary

In this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).

Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

PDF (1037 kb)

References

References
1 Mannucci PM, Gdovin S, Gringeri A, Colombo M, Mele A, Schinaia N, Ciavarella N, Emerson SU, Purcell RH. Transmission of hepatitis A to patients with hemophilia by factor VIII concentrates treated with organic solvent and detergent to inactivate viruses. The Italian Collaborative Group. Ann Intern Med 1994; 120: 1-7
2 Mannucci PM, Zannetti AR, Colombo M. and the Study Group of the Fondazione dell’ Emofilia Prospective study of hepatitis after factor VIII concentrate exposed to hot vapor. Br J Haematol 198 68: 427-430
3 Shopnick RI, Brettler DB, Bolivar E. Hepatitis C virus transmission by monoclonal-purified viral-attenuated factor VIII concentrate. Lancet 1995; 346: 645
4 Ludlam CA, Tucker J, Steel CM, Tedder RS, Cheingsong-Popow R, Weiss RA, McClelland DBL, Philip I, Prescott RJ. Human T-lymphotropic virus type III (HTLV-III) infection in seronegative hemophiliacs after transfusion of factor VIII. Lancet 1985; 02: 233-236
5 Kasper CK, Aledort LM, Aronson D, Counts RB, Edson JR, van EysJ, Fratantoni J, Green D, Hampton J, Hilgartner M, Levine P, Lazerson J, McMillan C, Penner J, Shapiro S, Shulman NR. A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh 1975; 34: 869
6 Verbruggen HW, Novakova IRO, Wessels JMC, Verbeek K, Polenewen RJ. Frequency of inhibitors in haemophiliacs. Lancet 1992; 339: 1501
7 Lusher JM, Arkin S, Abildgaard CF, Schwartz RS. and the Kogenate Previously untreated Patient Study Group. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia. N Engl J Med 1993; 328: 453-459
8 Ehrenforth S, Kreuz W, Scharrer I, Linde R, Funk M, Güngör T, Krackhardt B, Komhuber B. Incidence of development of factor VIII and factor IX inhibitor in hemophiliacs. Lancet 1992; 339: 594-598
9 Bray GL, Gomperts ED, Courter S, Gruppo R, Gordon EM, Manco-Johnson M, Shapiro A, Scheibel E, White III G, Lee M. and the Recombinate Study Group A multicenter study of recombinant factor VIII (Recombinate): Safety, Efficacy, and Inhibitor risk in previously untreated patients with hemophilia A. Blood 1994; 83: 2428-2435
10 Lusher J, Arkin S, Abildgaard CF, Hurst D. Kogenate treatment of previously untreated patients (PUPS) with hemophilia A: Update of safety, efficacy, and inhibitor development after seven study years. Blood 1996; 88 Suppl 01 442a (Abstract)
11 Addiego JE, Gomperts E, Liu SL, Bailey P, Courter SG, Lee ML, Neslund GG, Kingdon HS, Grifftith MJ. Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIII immunoaffinity chromatography. Thromb Haemost 1992; 67: 19-27
12 Lusher JM, Salzman PM. and the Monoclate Study Group Viral safety and inhibitor development associated with factor VIIIC ultra-purified from plasma in hemophiliacs previously unexposed to factor VIIIC concentrate. Semin Hematol 1990; 27 Suppl 02 1-7
13 Rosendaal FR, Nieuwenhuis HK, van denBergHM, Heijboer H, Mauser-Bunschoten EP, van derMeer J, Smit C, Strengers PF, Briet E. A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in the Netherlands. Blood 1993; 81: 2180-2186
14 Peerlinck K, Amout J, Gilles JG, Saint-Remy JM, Vermylen J. A higher than expected incidence of factor VIII inhibitors in multitransfused haemophilia A patients treated with an intermediate purity pasteurized factor VIII concentrate. Thromb Haemost 1993; 69: 115-118
15 White GC, Courter S, Bray GL, Lee M. Gomperts ED and the Recombinate Previously Treated Patient Study Group A multicenter study of recombinant factor VIII (Recombinate) in previously treated patients with hemophilia A. Thromb Haemost 1997; 77: 660-667
16 McMillan CW, Shapiro SS, Whitehurst D, Hoyer LW, Rao AV, Lazerson J. and the Hemophilia Study Group The natural history of factor VIII :C inhibitors in patients with hemophilia A: A national cooperative study. II. Observation on the initial development of FVIII :C inhibitors. Blood 1988; 71: 344-448
17 Giles AR, Rivard GE, Teitel J, Walker I, Lillicrap D, Dwyre L. and the Association of Hemophilia Clinic Directors of Cananda (AHCDC) The prevalence of factor VIII inhibitor detected in a national study to assess the effect of widespread introduction of high purity Factor VIII for the treatment of hemophilia A. Thromb Haemost 1995; 73: 1029 (Abstract)
18 Gürtler L. Blood-borne viral infections. Blood Coagul Fibrinolysis 1994; 05 (S 3) 5-10
19 Peerlinck K, Goubau P, Reybrouck R, Desmyter J, Vermylen J. Parvovirus B19 antibodies in patients with haemophilia A. Thromb Haemost 1995; 73: 555-556
20 Ragni MV, Koch WC, Jordan JA. Parvovirus B19 infection in patients with hemophilia. Transfusion 1996; 36: 238-241
21 Yee TT, Lee CA, Pasi KJ. Life-threatening human parvovirus B19 infection in immunocompetent haemophilia. Lancet 1995; 345: 794-795
22 Morfini M. In vitro characteristics of highly purified factor VIII concentrates. Ann Hematol 1991; 63: 123-125
23 Zakrzewska K, Azzi A, Patou G, Morfini M, Rafanelli D, Pattison JR. Human parvovirus B19 in clotting factor concentrates: B19 DNA detection by the nested polymerase chain reaction. Br J Haematol 1992; 81: 407-412
24 Eis-Hübinger AM, Sasowski U, Brackmann HH, Kaiser R, Matz B, Schneweis KE. Parvovirus B19 is frequently present in recombinant coagulation factor VIII products. Thromb Haemost 1996; 76: 1120
25 Azzi A, Ciappi S, Zakvrzewska K, Morfini M, Mariani G, Mannucci PM. Human parvovirus B19 infection in hemophiliacs first transfused with two high-purity, virally attenuated factor VIII concentrates. Am J Hematol 1992; 39: 228-230
26 Laurian Y, Dussaix E, Parquet A, Chalvon-Demercay A, d’Oiron R, Tchemia G. Transmission of human parvovirus B19 by plasma derived factor VIII concentrates. Nouv Rev Fr Hematol 1994; 36: 449-453
27 Flores G, Juarez JC, Montoro JB, Tusell JM, Altisent C, Juste C, Jardi R. Seroprevalence of parvovirus B19, cytomegalovirus, hepatitis A virus and hepatitis E virus antibodies in hemophiliacs treated exclusively with clotting-factor concentrates considered safe against human immunodeficiency and hepatitis C viruses. Hemophilia 1995; 01: 115-117
28 Williams MD, Cohen BJ, Beddall AC, Pasi KJ, Mortimer PP, Hill FGH. Transmission of human parvovirus B19 by coagulation factor Concentrates. Vox Sang 1990; 58: 177-181
29 Morfini M, Longo G, Rossi FerriniP, Azzi A, Zakrewska C, Ciappi S, Kolumban P. Hypoplastic anemia in a hemophiliac first infused with a solvent/detergent treated factor VIII concentrate: The role of human B19 parvovirus. Am J Hematol 1992; 39: 149-150
30 Santagostino E, Mannucci PM, Gringeri A, Azzi A, Morfini M. Eliminating parvovirus B19 from blood products. Lancet 1994; 343: 798
31 Schwartz RS, Abildgaard CF, Aledort LM, Arkin S, Bloom AL, Brackmann HH, Brettler DB, Fukui H, Hilgartner MW, Inwood MJ, Kasper CK, Kemoff PBA, Levine PH, Lusher JM, Mannucci PM, Scharrer I, MacKenzie MA, Pancham N, Kuo HS, Allred RU. and the Recombinant Factor VIII Study Group Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. N Engl J Med 1990; 323: 1800-1805
32 Fukui H, Yoshioka A, Shima M, Tanaka I, Koshihara K, Fukutake K, Fujimaki M. Clinical evaluation of recombinant human factor VIII (BAY w 6240) in the treatment of hemophilia A. Int J Hematol 1991; 54: 419-427
33 Brackmann HH, Aygören E, Scharrer I, Schwaab R, Hammerstein U, Oldenburg J. Two years’ experience with two recombinant factor VIII concentrates. Blood Coagul Fibrinolysis 1993; 04: 421-424