Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A

Richard S. Schwartz, Charles F. Abildgaard, Louis M. Aledort, Steven Arkin, Arthur L. Bloom, Hans H. Brackmann, Doreen B. Brettler, Hiromu Fukui, Margaret W. Hilgartner, Martin J. Inwood, Carol K. Kasper, Peter B A Kernoff, Peter H. Levine, Jeanne M. Lusher, Pier M. Mannucci, Inge Scharrer, Mary A. Mackenzie, Nazreen Pancham, Harng S. Kuo, Randy U. AllredJanet Harrison, Esther Rose, Stephanie Seremetis, Alice Forster, Justin Harrison, Johannes Egli, Ann Forsberg, Akira Yoshioka, Michio Fujimaki, Shojiro Ikematsu, Elizabeth Inwood, Sheldy I. Dietrich, Peter Mokary, Paul L. Giangrande, Indira Warner, Maureen O'Connor, Alessandro Gringeri, Loredana Simoni, Emel Aygören, Wolfhart Kreuz, Joseph E. Addiego, Jennifer M. Pearce, Thomas Coyle, Leticia P. Valdez, Carl E. Krill

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Current treatment of hemophilia A, a hereditary disorder affecting approximately 1 in 10,000 males, relies on plasma-derived factor VIII concentrates. We tested the safety and efficacy of a recombinant factor VIII preparation for the treatment of this disorder. Methods. We conducted the investigation in three stages: comparing the pharmacokinetics of plasma-derived and recombinant factor VIII, assessing the efficacy of recombinant factor VIII for home therapy, and assessing its efficacy for major surgical procedures and hemor-rhage. A total of 107 subjects with hemophilia, 20 of whom had not been treated previously, enrolled in the investigation. Results. The in vivo recovery and elimination half-lives of recombinant factor VIII equaled or exceeded those of plasma-derived factor VIII. Seventy-six subjects participated in a home-treatment program, using recombinant factor VIII for 69 to 807 days (median, 618); home diaries of 56 subjects treated for 5 months were analyzed. Of 540 bleeding episodes, 399 (73.9 percent) required only one treatment with recombinant factor VIII. The projected annual consumption of recombinant factor VIII was similar to that of plasma-derived factor VIII concentrate. Twenty-six subjects received recombinant factor VIII for 22 surgical procedures and 10 serious hemorrhages; hemostasis was excellent in all cases. De novo formation of inhibitors occurred in only 1 of 85 previously treated subjects. Inhibitor antibodies also developed in 6 of 21 children, 20 of whom had not previously been treated; 5 had low levels (≤7.5 Bethesda units) despite continued treatment with recombinant factor VIII. There was no evidence of new formation of antibody to foreign proteins, and recombinant factor VIII was well tolerated. Conclusions. Recombinant factor VIII has biologic activity comparable to that of plasma factor VIII and is safe and efficacious for the treatment of hemophilia A.

Original languageEnglish
Pages (from-to)1800-1805
Number of pages6
JournalNew England Journal of Medicine
Volume323
Issue number26
Publication statusPublished - Dec 27 1990

ASJC Scopus subject areas

  • Medicine(all)

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