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Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A

Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibito...

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Autores principales: Calvez, Thierry, Chambost, Hervé, d’Oiron, Roseline, Dalibard, Vincent, Demiguel, Virginie, Doncarli, Alexandra, Gruel, Yves, Huguenin, Yoann, Lutz, Patrice, Rothschild, Chantal, Vinciguerra, Christine, Goudemand, Jenny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777205/
https://www.ncbi.nlm.nih.gov/pubmed/29025913
http://dx.doi.org/10.3324/haematol.2017.174706
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author Calvez, Thierry
Chambost, Hervé
d’Oiron, Roseline
Dalibard, Vincent
Demiguel, Virginie
Doncarli, Alexandra
Gruel, Yves
Huguenin, Yoann
Lutz, Patrice
Rothschild, Chantal
Vinciguerra, Christine
Goudemand, Jenny
author_facet Calvez, Thierry
Chambost, Hervé
d’Oiron, Roseline
Dalibard, Vincent
Demiguel, Virginie
Doncarli, Alexandra
Gruel, Yves
Huguenin, Yoann
Lutz, Patrice
Rothschild, Chantal
Vinciguerra, Christine
Goudemand, Jenny
author_sort Calvez, Thierry
collection PubMed
description Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII <1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P=0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7–20.6) with Factane, 20.4% (95% CI: 14.0–29.1) with Advate, and 31.6% (95% CI: 23.5–41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide.
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spelling pubmed-57772052018-02-02 Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A Calvez, Thierry Chambost, Hervé d’Oiron, Roseline Dalibard, Vincent Demiguel, Virginie Doncarli, Alexandra Gruel, Yves Huguenin, Yoann Lutz, Patrice Rothschild, Chantal Vinciguerra, Christine Goudemand, Jenny Haematologica Article Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII <1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P=0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7–20.6) with Factane, 20.4% (95% CI: 14.0–29.1) with Advate, and 31.6% (95% CI: 23.5–41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide. Ferrata Storti Foundation 2018-01 /pmc/articles/PMC5777205/ /pubmed/29025913 http://dx.doi.org/10.3324/haematol.2017.174706 Text en Copyright© 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Article
Calvez, Thierry
Chambost, Hervé
d’Oiron, Roseline
Dalibard, Vincent
Demiguel, Virginie
Doncarli, Alexandra
Gruel, Yves
Huguenin, Yoann
Lutz, Patrice
Rothschild, Chantal
Vinciguerra, Christine
Goudemand, Jenny
Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title_full Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title_fullStr Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title_full_unstemmed Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title_short Analyses of the FranceCoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor VIII brands in boys with severe hemophilia A
title_sort analyses of the francecoag cohort support differences in immunogenicity among one plasma-derived and two recombinant factor viii brands in boys with severe hemophilia a
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777205/
https://www.ncbi.nlm.nih.gov/pubmed/29025913
http://dx.doi.org/10.3324/haematol.2017.174706
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