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Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study

Gouw, Samantha C.; van den Berg, H. Marijke; Fischer, Kathelijn; Auerswald, Guenter; Carcao, Manuel; Chalmers, Elizabeth; Chambost, Herve; Kurnik, Karin; Liesner, Ri and Petrini, Pia, et al. (2013) In Blood 121(20). p.4046-4055
Abstract
The objective of this study was to examine the association of the intensity of treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to prophylactic treatment, with the inhibitor incidence among previously untreated patients with severe hemophilia A. This cohort study aimed to include consecutive patients with a FVIII activity <0.01 IU/mL, born between 2000 and 2010, and observed during their first 75 FVIII exposure days. Intensive FVIII treatment of hemorrhages or surgery at the start of treatment was associated with an increased inhibitor risk (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 1.3-3.0). High-dose FVIII treatment was associated with a higher inhibitor risk than low-dose FVIII treatment... (More)
The objective of this study was to examine the association of the intensity of treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to prophylactic treatment, with the inhibitor incidence among previously untreated patients with severe hemophilia A. This cohort study aimed to include consecutive patients with a FVIII activity <0.01 IU/mL, born between 2000 and 2010, and observed during their first 75 FVIII exposure days. Intensive FVIII treatment of hemorrhages or surgery at the start of treatment was associated with an increased inhibitor risk (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 1.3-3.0). High-dose FVIII treatment was associated with a higher inhibitor risk than low-dose FVIII treatment (aHR, 2.3; 95% CI, 1.0-4.8). Prophylaxis was only associated with a decreased overall inhibitor incidence after 20 exposure days of FVIII. The association with prophylaxis was more pronounced in patients with low-risk F8 genotypes than in patients with high-risk F8 genotypes (aHR, 0.61, 95% CI, 0.19-2.0 and aHR, 0.85, 95% CI, 0.51-1.4, respectively). In conclusion, our findings suggest that in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment increases inhibitor risk and prophylactic FVIII treatment decreases inhibitor risk, especially in patients with low-risk F8 mutations. (Less)
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Contribution to journal
publication status
published
subject
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Blood
volume
121
issue
20
pages
4046 - 4055
publisher
American Society of Hematology
external identifiers
  • wos:000321871900009
  • scopus:84881014770
ISSN
1528-0020
DOI
10.1182/blood-2012-09-457036
language
English
LU publication?
yes
id
97ddb9b0-114a-41de-ae6d-278d73239334 (old id 4026975)
date added to LUP
2013-10-01 15:12:24
date last changed
2019-08-07 01:26:56
@article{97ddb9b0-114a-41de-ae6d-278d73239334,
  abstract     = {The objective of this study was to examine the association of the intensity of treatment, ranging from high-dose intensive factor VIII (FVIII) treatment to prophylactic treatment, with the inhibitor incidence among previously untreated patients with severe hemophilia A. This cohort study aimed to include consecutive patients with a FVIII activity &lt;0.01 IU/mL, born between 2000 and 2010, and observed during their first 75 FVIII exposure days. Intensive FVIII treatment of hemorrhages or surgery at the start of treatment was associated with an increased inhibitor risk (adjusted hazard ratio [aHR], 2.0; 95% confidence interval [CI], 1.3-3.0). High-dose FVIII treatment was associated with a higher inhibitor risk than low-dose FVIII treatment (aHR, 2.3; 95% CI, 1.0-4.8). Prophylaxis was only associated with a decreased overall inhibitor incidence after 20 exposure days of FVIII. The association with prophylaxis was more pronounced in patients with low-risk F8 genotypes than in patients with high-risk F8 genotypes (aHR, 0.61, 95% CI, 0.19-2.0 and aHR, 0.85, 95% CI, 0.51-1.4, respectively). In conclusion, our findings suggest that in previously untreated patients with severe hemophilia A, high-dosed intensive FVIII treatment increases inhibitor risk and prophylactic FVIII treatment decreases inhibitor risk, especially in patients with low-risk F8 mutations.},
  author       = {Gouw, Samantha C. and van den Berg, H. Marijke and Fischer, Kathelijn and Auerswald, Guenter and Carcao, Manuel and Chalmers, Elizabeth and Chambost, Herve and Kurnik, Karin and Liesner, Ri and Petrini, Pia and Platokouki, Helen and Altisent, Carmen and Oldenburg, Johannes and Nolan, Beatrice and Perez Garrido, Rosario and Mancuso, M. Elisa and Rafowicz, Anne and Williams, Mike and Clausen, Niels and Middelburg, Rutger A. and Ljung, Rolf and van der Bom, Johanna G.},
  issn         = {1528-0020},
  language     = {eng},
  number       = {20},
  pages        = {4046--4055},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study},
  url          = {http://dx.doi.org/10.1182/blood-2012-09-457036},
  volume       = {121},
  year         = {2013},
}