RT Journal Article
T1 A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.
A1 Peyvandi, Flora
A1 Mannucci, Pier M
A1 Garagiola, Isabella
A1 El-Beshlawy, Amal
A1 Elalfy, Mohsen
A1 Ramanan, Vijay
A1 Eshghi, Peyman
A1 Hanagavadi, Suresh
A1 Varadarajan, Ramabadran
A1 Karimi, Mehran
A1 Manglani, Mamta V
A1 Ross, Cecil
A1 Young, Guy
A1 Seth, Tulika
A1 Apte, Shashikant
A1 Nayak, Dinesh M
A1 Santagostino, Elena
A1 Mancuso, Maria Elisa
A1 Sandoval Gonzalez, Adriana C
A1 Mahlangu, Johnny N
A1 Bonanad Boix, Santiago
A1 Cerqueira, Monica
A1 Ewing, Nadia P
A1 Male, Christoph
A1 Owaidah, Tarek
A1 Soto Arellano, Veronica
A1 Kobrinsky, Nathan L
A1 Majumdar, Suvankar
A1 Perez Garrido, Rosario
A1 Sachdeva, Anupam
A1 Simpson, Mindy
A1 Thomas, Mathew
A1 Zanon, Ezio
A1 Antmen, Bulent
A1 Kavakli, Kaan
A1 Manco-Johnson, Marilyn J
A1 Martinez, Monica
A1 Marzouka, Esperanza
A1 Mazzucconi, Maria G
A1 Neme, Daniela
A1 Palomo Bravo, Angeles
A1 Paredes Aguilera, Rogelio
A1 Prezotti, Alessandra
A1 Schmitt, Klaus
A1 Wicklund, Brian M
A1 Zulfikar, Bulent
A1 Rosendaal, Frits R
K1 Adulto
K1 Anciano
K1 Anticuerpos neutralizantes
K1 Niño
K1 Adolescente
K1 Niño preescolar
K1 Relación dosis-respuesta de medicamentos
K1 Farmacoterapia combinada
K1 Factor VIII
K1 Hemofilia A
K1 Hemorragia
K1 Humanos
K1 Incidencia
K1 Lactante
K1 Inyecciones subcutáneas
K1 Isoanticuerpos
K1 Masculino
K1 Mediana edad
K1 Modelos de riesgos proporcionales
K1 Adulto joven
K1 Factor de von Willebrand
AB BACKGROUNDThe development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy.METHODSWe conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites.RESULTSOf 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00).CONCLUSIONSPatients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).
PB Massachusetts Medical Society
SN 0028-4793
YR 2016
FD 2016-05-26
LK http://hdl.handle.net/10668/2671
UL http://hdl.handle.net/10668/2671
LA en
NO Peyvandi F, Mannucci PM, Garagiola I, El-Beshlawy A, Elalfy M, Ramanan V, et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med. 2016; 374(21):2054-64
NO Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;Comment in:Hemophilia Therapy--Navigating Speed Bumps on the Innovation Highway. [N Engl J Med. 2016]
NO Supported by the nonprofit Angelo Bianchi Bonomi Foundation and the Italian Ministry of Health (Progetti Finalizzati and Agenzia Italiana del Farmaco). Grifols, Kedrion Biopharma, and LFB provided unrestricted grants to the Angelo Bianchi Bonomi Foundation.
DS RISalud
RD Apr 10, 2025