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DOI: 10.1055/s-0038-1650217
Safety and Efficacy of Monoclonal Antibody Purified Factor IX Concentrate in Previously Untreated Patients with Hemophilia B
Publikationsverlauf
Received 28. April 1995
Accepted after resubmission 28. September 1995
Publikationsdatum:
10. Juli 2018 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199601/lookinside/thumbnails/10-1055-s-0038-1650217-1.jpg)
Summary
The safety and efficacy of a monoclonal antibody purified factor IX concentrate were evaluated in two continuing trials of 32 previously untreated patients with mild, moderate, or severe hemophilia B. Patients were evaluated every 2 weeks for 24 weeks and every 3 months thereafter for at least 1 year. No patients became positive for human immunodeficiency virus antibody or hepatitis C virus antibody during the trial. Two patients developed a false-positive hepatitis B core antibody, one transiently, but neither had elevated levels of alanine aminotransferase (ALT). None of the 25 patients evaluable for non-A, non-B, non-C hepatitis by strict International Society of Thrombosis and Hemostasis criteria developed elevated levels of ALT indicative of posttransfusion infection. Anaphylaxis occurred in one subject who also developed an inhibitor to factor IX (19.3 Bethesda units). Five of the eight adverse events reported (63%) were mild in severity, and the relationship of three of these to therapy was considered remote. Hemostasis with monoclonal antibody purified factor IX concentrate was excellent in all patients.
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References
- 1 Heimburger N, Karges HE. Strategies to produce virus-safe blood derivatives. Curr Stud Hematol Blood Transfus 1989; 56: 23-33
- 2 Azzi A, Ciappi K, Zakvrzewska K, Morfini M, Mariani G, Mannucci PM. Human parvovirus B19 infection in hemophiliacs first infused with two high-purity, virally attenuated factor VIII concentrates. Am J Hematol 1992; 39: 228-230
- 3 Fricke WA, Lamb MA. Viral safety of clotting factor concentrates. Semin Thromb Haemost 1993; 19: 54-61
- 4 Lee CA, Kemoff PBA. Viral hepatitis and haemophilia. Br Med Bull 1990; 46: 408-422
- 5 Aledort LM, Levine PH, Hilgartner M, Blatt P, Spero JA, Goldberg JD, Bianchi L, Desmet V, Scheuer P, Popper H, Berk PD. A study of liver biopsies and liver disease among hemophiliacs. Blood 1985; 66: 367-372
- 6 Mannucci PM, Colombo M. Virucidal treatment of clotting factor concentrates. Lancet 1988; pp 782-785
- 7 Mannucci PM, Colombo M. Revision of the protocol recommended for studies of safety from hepatitis of clotting factor concentrates. Thromb Haemost 1989; 61: 532-534
- 8 Fletcher ML, Trowell JM, Craske J, Pavier K, Rizza CR. Non-A, non-B hepatitis after transfusion of factor VIII in infrequently treated patients. Br Med J 1983; 287: 1754-1757
- 9 Kemoff PBA, Lee CA, Karayiannis P, Thomas HC. High risk of non-A, non-B hepatitis after a first exposure to volunteer or commercial clotting factor concentrates: effects of prophylactic immune semm globulin. Br J Haematol 1985; 60: 469-479
- 10 Kasper CK, Lusher JM. the Transfusion Practices Committee Recent evolution of clotting factor concentrates for hemophilia A and B. Transfusion 1993; 33: 422-434
- 11 Mannucci PM. Viral safety of plasma-derived and recombinant products used in the management of haemophilia A and B. Haemophilia 1995; 1: 14-20
- 12 Mannucci PM, Morfini M, Gatti L, Rafanelli D, Colombo M, Geroldi D, Einarsson M, Zanetti AR. No hepatitis after treatment with a modified factor IX concentrate in previously untreated hemophiliacs. Ann Intern Med 1985; 103: 226-227
- 13 Skidmore SJ, Pasi KJ, Mawson SJ, Williams MD, Hill FGH. Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis. J Med Virol 1990; 30: 50-52
- 14 Morfini M, Longo G, Berntorp E, Cinotti S, Filimberti E, Messori A, Nilsson IM, Ferrini RR. Pharmacokinetics, thrombogenicity and safety of a double-treated prothrombin complex concentrate. Thromb Res 1993; 71: 175-184
- 15 Hrinda ME, Huang C, Tarr GC, Weeks R, Feldman F, Schreiber AB. Pre-clinical studies of monoclonal antibody purified factor IX, MononineTM . Semin Hematol 1991; 28 (Suppl) (Suppl. 06) 06-14
- 16 Spronk AM, Schmidt L, Krenc C, Pavlis-Jenkins L, Brady J, Taskar S, Angus-Finn L, Mimms L. Improvements in detection of antibody to hepatitis B core antigen by treating specimens with reducing agent in an automated microparticle enzyme immunoassay. J Clin Microbiol 1991; 29: 611-616
- 17 Weare JA, Robertson EF, Madsen G, Hu R, Decker RH. Improvement in the specificity of assays for detection of antibody to hepatitis B core antigen. J Clin Microbiol 1991; 29: 600-604
- 18 Robertson EF, Weare JA, Randeil R, Holland PV, Madsen G, Decker RH. Characterization of a reduction-sensitive factor from human plasma responsible for apparent false activity in competitive assays for antibody to hepatitis B core antigen. J Clin Microbiol 1991; 29: 605-610
- 19 Horowitz MS, Rooks C, Horowitz B, Hilgartner MW. Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. Lancet 1988; 186-188
- 20 Mannucci PM, Schimpf K, Brettler DB, Ciavarella N, Colombo M, Hasch-ke F, Lechner K, Lusher J, Weissbach G. the International Study Group Low risk for hepatitis C in hemophiliacs given a high-purity, pasteurized factor VIII concentrate. Ann Intern Med 1990; 113: 27-32
- 21 Mariani G, Di Paolantonio T, Baklaya R, Morfini M, Mannucci PM. the Ad Hoc Study Group of the Fondazione dell’Emofilia Prospective study of the evaluation of hepatitis C virus infectivity in high-purity, solvent/detergent-treated factor VIII concentrate: parallel evaluation of other markers for lipid-enveloped and non-lipid-enveloped viruses. Transfusion 1993; 33: 814-818
- 22 Mannucci PM, Schimpf K, Abe T, Aledort LM, Anderle K, Brettler DB, Hilgartner MW, Kernoff PBA, Kunschak M, McMillan CW, Preston FE, Rivard GE. the International Investigator Group Low risk of viral infection after administration of vapor-heated factor VIII concentrate. Transfusion 1992; 32: 134-138
- 23 Lusher JM, Salzman PM. the Monoclate Study Group Viral safety and inhibitor development associated with factor VIIIC ultra-purified from plasma in hemophiliacs previously unexposed to factor VIIIC concentrates. Semin Hematol 1990; 27 (Suppl) (Suppl. 02) 1-7
- 24 Goudemand J, Parquet A, d’Oiron R, Stieltjes N, Guerois C, Fonlupt J, Alcalay M, Negrier C, Cazenave JP, Briquel ME, Fressinaud E. Hepatitis A in French hemophiliacs. Vox Sang 1994; 67 (Suppl) (Suppl. 01) 09-13
- 25 D’Argenio P, Esposito D, Mele A, Ortolani G, Adamo B, Rapicetta M, Forte P, Pisani A, Soldo L, Sarrecchia B, Stroffolini T, Pasquini P. Decline in the exposure to hepatitis A and B infections in children in Naples, Italy. Public Health 1989; 103: 385-389
- 26 Cohen BJ, Buckley MM. The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 1988; 25: 151-153
- 27 Schwarz TF, Roggendorf M, Deinhardt F. Untitled. (Letter to the Editor). Lancet 1987; 739
- 28 Becton D, Manno C, Green D, Gilchrist G, Kulkami R, Priest J, Sexauer C, Schlueter W, Norton F. Viral safety of an affinity-purified coagulation factor IX concentrate (Alphanine® SD). Blood 1994; 84 (10) 198
- 29 Shapiro A. The International Factor Safety Group Vapor heated interme-diate-purity factor IX concentrate tested in a safety study monitoring transfusion-related viral infection in previously untreated hemophiliacs. Thromb Haemost 1993; 69: 943
- 30 Sultan Y. the French Hemophilia Study Group Prevalence of inhibitors in a population of 3435 hemophilia patients in France. Thromb Haemost 1992; 67: 600-602
- 31 Rosendaal FR, Nieuwenhuis HK, van den Berg HM, Heijboer H, Mauser-Bunschoten EP, van der Meer J, Smit C, Strengers PFW, Briet E. Dutch Hemophilia Study Group A sudden increase in factor VIII inhibitor development in multitransfused hemophilia A patients in the Netherlands. Blood 1993; 81: 2180-2186
- 32 Ljung RCR. Hemophilia B treatment issues and options: gene mutations and inhibitor formation. Acta Haematol (in press)
- 33 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 inhibitors in haemophiliacs. Lancet 1992; 339: 594-598