title: Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: the RODIN study.
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.
authors.affiliation: Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Gouw
authors.forename: H Marijke
authors.initials: HM
authors.lastname: van den Berg
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Fischer
authors.forename: Günter
authors.initials: G
authors.lastname: Auerswald
authors.forename: Manuel
authors.initials: M
authors.lastname: Carcao
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Chalmers
authors.forename: Hervé
authors.initials: H
authors.lastname: Chambost
authors.forename: Karin
authors.initials: K
authors.lastname: Kurnik
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.forename: Pia
authors.initials: P
authors.lastname: Petrini
authors.forename: Helen
authors.initials: H
authors.lastname: Platokouki
authors.forename: Carmen
authors.initials: C
authors.lastname: Altisent
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nolan
authors.forename: Rosario Pérez
authors.initials: RP
authors.lastname: Garrido
authors.forename: M Elisa
authors.initials: ME
authors.lastname: Mancuso
authors.forename: Anne
authors.initials: A
authors.lastname: Rafowicz
authors.forename: Mike
authors.initials: M
authors.lastname: Williams
authors.forename: Niels
authors.initials: N
authors.lastname: Clausen
authors.forename: Rutger A
authors.initials: RA
authors.lastname: Middelburg
authors.forename: Rolf
authors.initials: R
authors.lastname: Ljung
authors.forename: Johanna G
authors.initials: JG
authors.lastname: van der Bom
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000378:metabolism*; D018890:Chemoprevention / Q000009:adverse effects; D002648:Child; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005169:Factor VIII / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology* / Q000378:metabolism; D006470:Hemorrhage / Q000097:blood / Q000453:epidemiology / Q000378:metabolism / Q000517:prevention & control*; D006801:Humans; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D005169:Factor VIII