TY - JOUR
T1 - Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study
AU - Gouw, Samantha C.
AU - van den Berg, H. Marijke
AU - Fischer, Kathelijn
AU - Auerswald, Günter
AU - Carcao, Manuel
AU - Chalmers, Elizabeth
AU - Chambost, Hervé
AU - Kurnik, Karin
AU - Liesner, R. I.
AU - Petrini, Pia
AU - Platokouki, Helen
AU - Altisent, Carmen
AU - Oldenburg, Johannes
AU - Nolan, Beatrice
AU - Garrido, Rosario Pérez
AU - Mancuso, M. Elisa
AU - Rafowicz, Anne
AU - Williams, Mike
AU - Clausen, Niels
AU - Middelburg, Rutger A.
AU - Ljung, Rolf
AU - van der Bom, Johanna G.
AU - AUTHOR GROUP
AU - Altisent, C.
AU - Auerswald, G.
AU - Carcao, M.
AU - Chalmers, E.
AU - Chambost, H.
AU - Cid, A.
AU - Claeyssens, S.
AU - Clausen, N.
AU - Fischer, K.
AU - van Geet, Ch
AU - Peerlinck, K.
AU - Kenet, G.
AU - Kobelt, R.
AU - Kreuz, W.
AU - Escuriola, C.
AU - Kurnik, K.
AU - Liesner, R.
AU - Ljung, R.
AU - Mäkipernaa, A.
AU - Molinari, A.
AU - Muntean, W.
AU - Nolan, B.
AU - Oldenburg, J.
AU - Pérez Garrido, R.
AU - Petrini, P.
AU - Platokouki, H.
AU - Rafowicz, A.
AU - Rivard, G.
PY - 2013
Y1 - 2013
N2 - 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
AB - 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
U2 - https://doi.org/10.1182/blood-2012-09-457036
DO - https://doi.org/10.1182/blood-2012-09-457036
M3 - Article
C2 - 23553768
SN - 0006-4971
VL - 121
SP - 4046
EP - 4055
JO - Blood
JF - Blood
IS - 20
ER -