Impact of Treatment Intensity and Factor VIII Products On the Development On High Titre Inhibitors in Children with Severe Hemophilia A: Results of a Non-Concurrent Cohort Study
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Medientyp:
E-Artikel
Titel:
Impact of Treatment Intensity and Factor VIII Products On the Development On High Titre Inhibitors in Children with Severe Hemophilia A: Results of a Non-Concurrent Cohort Study
Erschienen in:
Blood, 114 (2009) 22, Seite 1303-1303
Sprache:
Englisch
DOI:
10.1182/blood.v114.22.1303.1303
ISSN:
0006-4971;
1528-0020
Entstehung:
Anmerkungen:
Beschreibung:
Abstract Abstract 1303 Poster Board I-325 Background A number of environmental and genetic factors have been identified to influence inhibitor development in children with severe hemophilia A (HA): among them, individual therapeutic regimens and the use of different factor VIII products have been controversially discussed. Methods In the present multicenter cohort study we evaluated the impact of i) treatment intensity [median individual dose administered during the first 6 to 8 weeks] and ii) type of factor VIII product [plasma-derived (pd); recombinant-derived (r)] on the risk of high-titre inhibitor development in 150 previously untreated patients with severe hemophilia A (HA) consecutively ascertained between 1982 and 2007 from five German catchment areas. Patients were followed over a period of 200 exposure days from HA onset. Study endpoint was inhibitor-free survival time related to treatment with adjustment for treatment period. Plasma levels of factor VIII were determined by one-stage clotting assays. Inhibitor testing was performed at least monthly to 3 monthly when on therapy using the Bethesda method or its modification [Nijmegen]: The lower detection limit was set at 0.6 Bethesda units [BU]. A peak inhibitor titer of > 5 BU was defined as high responder [HR]. A positive inhibitor testing was stated when an inhibitor was measured at least in two independent follow-up visits. The cumulative inhibitor-free survival was calculated using multivariate Cox regression [hazard ratio (HR) and 95% confidence intervals [CIs]]. Results During the follow-up period 30 of 150 children (20.0%) developed a high titre inhibitor. In univariate analysis the median dose increase per IU/kgbw significantly increased the hazard towards HR inhibitor development [HR/CI: 1.08/1.05-1.11]. In addition, 14 of 52 children treated with rFVIII concentrates (27%) versus 16 of 98 children (16.3%) treated with pdFVIII concentrates developed HR during the observation period [HR/CI: 1.9/0.9-3.9]. In multivariate analysis treatment intensity adjusted for FVIII products and treatment period were independently associated with the development of clinical meaningful inhibitors [HR/95%CI: 1.08/1.1-1.1]. Conclusion Data presented here support the hypothesis that clinical meaningful inhibitor development is of multifactorial origin and that treatment intensity plays a major role. Disclosures Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism.