Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study
Samantha C Gouw, H Marijke van den Berg, Kathelijn Fischer, Günter Auerswald, Manuel Carcao, Elizabeth Chalmers, Hervé Chambost, Karin Kurnik, Ri Liesner, Pia Petrini, Helen Platokouki, Carmen Altisent, Johannes Oldenburg, Beatrice Nolan, Rosario Pérez Garrido, M Elisa Mancuso, Anne Rafowicz, Mike Williams, Niels Clausen, Rutger A Middelburg, Rolf Ljung, Johanna G van der Bom, PedNet and Research of Determinants of INhibitor development (RODIN) Study Group, C Altisent, G Auerswald, M Carcao, E Chalmers, H Chambost, A Cid, S Claeyssens, N Clausen, K Fischer, Ch van Geet, K Peerlinck, G Kenet, R Kobelt, W Kreuz, C Escuriola, K Kurnik, R Liesner, R Ljung, A Mäkipernaa, A Molinari, W Muntean, B Nolan, J Oldenburg, R Pérez Garrido, P Petrini, H Platokouki, A Rafowicz, G Rivard, E Santagostino, M E Mancuso, A Thomas, M Williams, S C Gouw, J G van der Bom, H M van den Berg, Samantha C Gouw, H Marijke van den Berg, Kathelijn Fischer, Günter Auerswald, Manuel Carcao, Elizabeth Chalmers, Hervé Chambost, Karin Kurnik, Ri Liesner, Pia Petrini, Helen Platokouki, Carmen Altisent, Johannes Oldenburg, Beatrice Nolan, Rosario Pérez Garrido, M Elisa Mancuso, Anne Rafowicz, Mike Williams, Niels Clausen, Rutger A Middelburg, Rolf Ljung, Johanna G van der Bom, PedNet and Research of Determinants of INhibitor development (RODIN) Study Group, C Altisent, G Auerswald, M Carcao, E Chalmers, H Chambost, A Cid, S Claeyssens, N Clausen, K Fischer, Ch van Geet, K Peerlinck, G Kenet, R Kobelt, W Kreuz, C Escuriola, K Kurnik, R Liesner, R Ljung, A Mäkipernaa, A Molinari, W Muntean, B Nolan, J Oldenburg, R Pérez Garrido, P Petrini, H Platokouki, A Rafowicz, G Rivard, E Santagostino, M E Mancuso, A Thomas, M Williams, S C Gouw, J G van der Bom, H M van den Berg
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 (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.
Source: PubMed