Contributions
Abstract: PB1744
Type: Publication Only
Background
Development of neutralizing anti-factor VIII alloantibodies (inhibitor; INH) is the most challenging complication of haemophilia replacement therapy (HRT). It occurs in up to 30% of severe haemophilia A (HA) patients. Data published recently indicate that immunotolerance induction (ITI) is effective in 62–87% of cases.
Aims
To assess the rate of successful ITI in boys with severe HA treated with full length recombinant FVIII (octocog α) in all Polish Paediatric Haemophilia Care Centres between 2011-2016.
Methods
From 2011 to 2016 in all Polish Paediatric Haemophilia Care Centres 14/88 (15.9%) boys with severe HA on prophylaxis or on demond treatment with octocog α developed INH after 3 - 489 (median 20) exposure days (EDs). Twelve of them (85.7%) were high responders with the peak inhibitor titre (PIT) 5,88 - 716.8 (median 20.1) BU/ml. Two patients were low responders (14,3%) and had PIT 2.8 and 3.02BU/ml. All except one boys were Caucasians and only one had a positive family history of INH formation. Characteristics of patients is given in table 1.
Patient | Age at: 1st dose of FVIII / start of prophylaxis [mth] | Peak inhibitor titer BU/ml | Number of EDs at INH diagnosis | Type of treatment | Surgery | High doses of FVIII due to bleeding | Factor VIII given on: first day of infection / day of vaccination |
1 | 0.1 / 22.8 | 2,8 | 21 | P | subgaleal | Y / N | |
2 | 11.9 / 11.9 | 3.02 | 10 | P | N / N | ||
3 | 11.9 / 11.9 | 5,88 | 20 | P | N / N | ||
4 | 5 / - | 6,4 | 3 | OD | intramuscular | N / N | |
5 | 32.9 / - | 7.6 | 20 | OD | GI | N / N | |
6 | 0 / - | 11.0 | 21 | OD | CNS | N / N | |
7 | 11.6 / 11.6 | 14 | 489 | P | CVA | N / N | |
8 | 11.9 / 12.6 | 15.84 | 6 | OD + P | oral mucosa and frenulla of the mouth | N / N | |
9 | 4.2 / - | 20,1 | 22 | OD | CVA | Y / N | |
10 | 0.1 / 10.6 | 22 | 21 | OD + P | subgaleal | N / N | |
11 | 12.2 / 12.2 | 37 | 15 | P | N / N | ||
12 | 12.1 / 12.1 | 88,96 | 14 | P | N / N | ||
13 | 3.4 / 7.1 | 131 | 10 | P | N / N | ||
14 | 11,2 / - | 252,5 | 20 | OD | massive to scrotum + after venopuncture | N / N |
Results
INH titres prior to ITI were 1.2 - 37 (median 6,75) BU/ml. One of low responders eliminated INH spontaneously, 1 patient is waiting for ITI initiation. ITI with octocog α was initiated in 12/14 boys after 0.2 to 8.2 (median 2.0) months from INH diagnosis and completed in 9 patients. Three patients are still on ITI. INH eradication was observed in 7/9 (77.8%) of those who completed ITI. Eradication of INH was not achieved in 2 patients; both have already started prophylaxis with activated prothrombin complex concentrate (APCC). The remaining 3 patients are still on ITI. All 7 patients after successful ITI were put back on prophylaxis with octocog α.
Conclusion
- Octocog α is effective in induction of immunotolerance in severe haemophilia A boys who developed inhibitor on prophylaxis with octocog α.
Session topic: 33. Bleeding disorders (congenital and acquired)
Keyword(s): Inhibitor, Immunologic tolerance, Hemophilia A
Abstract: PB1744
Type: Publication Only
Background
Development of neutralizing anti-factor VIII alloantibodies (inhibitor; INH) is the most challenging complication of haemophilia replacement therapy (HRT). It occurs in up to 30% of severe haemophilia A (HA) patients. Data published recently indicate that immunotolerance induction (ITI) is effective in 62–87% of cases.
Aims
To assess the rate of successful ITI in boys with severe HA treated with full length recombinant FVIII (octocog α) in all Polish Paediatric Haemophilia Care Centres between 2011-2016.
Methods
From 2011 to 2016 in all Polish Paediatric Haemophilia Care Centres 14/88 (15.9%) boys with severe HA on prophylaxis or on demond treatment with octocog α developed INH after 3 - 489 (median 20) exposure days (EDs). Twelve of them (85.7%) were high responders with the peak inhibitor titre (PIT) 5,88 - 716.8 (median 20.1) BU/ml. Two patients were low responders (14,3%) and had PIT 2.8 and 3.02BU/ml. All except one boys were Caucasians and only one had a positive family history of INH formation. Characteristics of patients is given in table 1.
Patient | Age at: 1st dose of FVIII / start of prophylaxis [mth] | Peak inhibitor titer BU/ml | Number of EDs at INH diagnosis | Type of treatment | Surgery | High doses of FVIII due to bleeding | Factor VIII given on: first day of infection / day of vaccination |
1 | 0.1 / 22.8 | 2,8 | 21 | P | subgaleal | Y / N | |
2 | 11.9 / 11.9 | 3.02 | 10 | P | N / N | ||
3 | 11.9 / 11.9 | 5,88 | 20 | P | N / N | ||
4 | 5 / - | 6,4 | 3 | OD | intramuscular | N / N | |
5 | 32.9 / - | 7.6 | 20 | OD | GI | N / N | |
6 | 0 / - | 11.0 | 21 | OD | CNS | N / N | |
7 | 11.6 / 11.6 | 14 | 489 | P | CVA | N / N | |
8 | 11.9 / 12.6 | 15.84 | 6 | OD + P | oral mucosa and frenulla of the mouth | N / N | |
9 | 4.2 / - | 20,1 | 22 | OD | CVA | Y / N | |
10 | 0.1 / 10.6 | 22 | 21 | OD + P | subgaleal | N / N | |
11 | 12.2 / 12.2 | 37 | 15 | P | N / N | ||
12 | 12.1 / 12.1 | 88,96 | 14 | P | N / N | ||
13 | 3.4 / 7.1 | 131 | 10 | P | N / N | ||
14 | 11,2 / - | 252,5 | 20 | OD | massive to scrotum + after venopuncture | N / N |
Results
INH titres prior to ITI were 1.2 - 37 (median 6,75) BU/ml. One of low responders eliminated INH spontaneously, 1 patient is waiting for ITI initiation. ITI with octocog α was initiated in 12/14 boys after 0.2 to 8.2 (median 2.0) months from INH diagnosis and completed in 9 patients. Three patients are still on ITI. INH eradication was observed in 7/9 (77.8%) of those who completed ITI. Eradication of INH was not achieved in 2 patients; both have already started prophylaxis with activated prothrombin complex concentrate (APCC). The remaining 3 patients are still on ITI. All 7 patients after successful ITI were put back on prophylaxis with octocog α.
Conclusion
- Octocog α is effective in induction of immunotolerance in severe haemophilia A boys who developed inhibitor on prophylaxis with octocog α.
Session topic: 33. Bleeding disorders (congenital and acquired)
Keyword(s): Inhibitor, Immunologic tolerance, Hemophilia A