A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A

• Published in: The New England journal of medicine Vol. 374; no. 21; pp. 2054 - 2064
• Main Authors: Peyvandi, Flora, Mannucci, Pier M, Garagiola, Isabella, El-Beshlawy, Amal, Elalfy, Mohsen, Ramanan, Vijay, Eshghi, Peyman, Hanagavadi, Suresh, Varadarajan, Ramabadran, Karimi, Mehran, Manglani, Mamta V, Ross, Cecil, Young, Guy, Seth, Tulika, Apte, Shashikant, Nayak, Dinesh M, Santagostino, Elena, Mancuso, Maria Elisa, Sandoval Gonzalez, Adriana C, Mahlangu, Johnny N, Bonanad Boix, Santiago, Cerqueira, Monica, Ewing, Nadia P, Male, Christoph, Owaidah, Tarek, Soto Arellano, Veronica, Kobrinsky, Nathan L, Majumdar, Suvankar, Perez Garrido, Rosario, Sachdeva, Anupam, Simpson, Mindy, Thomas, Mathew, Zanon, Ezio, Antmen, Bulent, Kavakli, Kaan, Manco-Johnson, Marilyn J, Martinez, Monica, Marzouka, Esperanza, Mazzucconi, Maria G, Neme, Daniela, Palomo Bravo, Angeles, Paredes Aguilera, Rogelio, Prezotti, Alessandra, Schmitt, Klaus, Wicklund, Brian M, Zulfikar, Bulent, Rosendaal, Frits R
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 26-05-2016
• Subjects: Adolescent; Adult; Aged; Alloantibodies; Antibodies, Neutralizing - blood; Child; Child, Preschool; Clinical trials; Coagulation factors; Dose-Response Relationship, Drug; Drug therapy; Drug Therapy, Combination; Evidence-based medicine; Factor VIII - antagonists & inhibitors; Factor VIII - immunology; Factor VIII - therapeutic use; Factor VIII deficiency; FDA approval; Health risk assessment; Hemophilia; Hemophilia A - complications; Hemophilia A - drug therapy; Hemophilia A - immunology; Hemorrhage - etiology; Humans; Immunoglobulins; Incidence; Infant; Inhibitor drugs; Injections, Subcutaneous - adverse effects; Isoantibodies - analysis; Male; Middle Aged; Patients; Proportional Hazards Models; Regression analysis; Von Willebrand factor; von Willebrand Factor - therapeutic use; Young Adult
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1516437

In a randomized, multicenter trial involving boys with severe hemophilia A, the incidence of neutralizing antibodies to factor VIII was 87% higher with recombinant factor VIII products than with plasma-derived factor VIII products.
Hemophilia A is an inherited bleeding disorder characterized by plasma deficiency of coagulation factor VIII.
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A major complication in 30% of patients is the occurrence of alloantibodies (inhibitors) that inactivate factor VIII activity and may nullify replacement therapy.
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Risk factors include unmodifiable patient-related factors such as residual plasma factor VIII concentration and gene mutation.
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Putative treatment-related risk factors are early replacement therapy and the source of factor VIII (i.e., human plasma or recombinant DNA technology).
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Experimental studies have shown that plasma-derived factor VIII in complex with the chaperone protein von Willebrand factor, which masks . . .