Early long-term XXXX prophylaxis in haemophilia A @entity1 with inhibitor after failing immune tolerance induction: A prospective clinical case series.

@entity1 @entity33081 @entity548 @entity16 @entity2720 @entity715
Persistent high-titre inhibitors after immune tolerance induction (ITI) increase the risks of @entity548 and @entity2720 , resulting in high morbidity and mortality. Long-term prophylaxis with bypassing agents may avert these risks. This study was performed to assess the effectiveness and safety of early prophylaxis with @entity33081 in preventing @entity548 and @entity16 after failed ITI. Seven paediatric @entity1 proceeded immediately after failed ITI to long-term @entity33081 prophylaxis at 60-100 IU kg(-1) dosages and various dosing intervals depending upon @entity548 tendency. Bleeding episodes and joint status were assessed. Thrombin generation assays (TGA) were also used to gauge treatment response. @entity33081 prophylaxis was commenced at a median age of 6.0 years (range, 1.5-11.8 years) and continued for a median duration of 6.9 years (range, 0.8-17.1 years). The mean annual incidence of @entity548 was 1.5 episodes per year with a 95% CI of 0.7-3.0 episodes per year. Muscle @entity548 incidence was 0.9 episodes per year (CI, 0.6-1.2 episodes per year). No @entity1 experienced major @entity16 during prophylaxis. Median Pettersson and orthopaedic joint scores at the last follow-up evaluation were 4 (range, 0-12) and 2 (range, 0-4) respectively. Endogenous thrombin potential (ETP) measured by TGA exceeded 80% of normal after @entity33081 infusion in the majority of the @entity1 . Between regular prophylactic infusions, mean trough ETP equalled 2.6 fold of the inhibitor plasma control mean. @entity33081 prophylaxis was well-tolerated without serious @entity715 or other complications. The only adverse event involved venous access. Therefore early long-term @entity33081 prophylaxis is valuable in controlling @entity548 and preserving joint integrity in young @entity1 failing ITI.
