Immune tolerance outcome and economics retrospective registry (iter-study) of patients with haemophilia A (ha) and factor VIII inhibitors

Introduction: Immune tolerance induction (ITI) is the only proven strategy for eradicating inhibitors in high responding HA patients. If successful, this results in substantial improvement in the patient’s quality of life and a marked reduction in long-term treatment costs. However, ITI treatment is very expensive, the optimal regimen has yet to be determined and few data are available on host and treatment-related variables that may influence ITI outcome. The EHTSB has therefore established an Immune Tolerance and Economics Retrospective (ITER) Registry of HA patients undergoing a ITI course, to provide more information. Methods: HA patients (pts) who underwent ITI, irrespective of dosing regimen or type of FVIII, are eligible. The cost of ITI and FVIII or by-passing agents used for treatment or prophylaxis of bleeds are calculated and costs in the 12-months period before and following the ITI course are compared. Results: 26 patients have been entered so far; 23 had high-responding inhibitors. 14 had no family history of inhibitors; 12 no family history of ITI treatment. A null mutation was present in 13/20 pts with known F8 genotype. Median age at ITI was 2.8 years (range: 0.9–38.4). Recombinant products were used for the first ITI course in 20 pts; plasma-derived products in 6 and a FVIII/VWF product in 4. Doses of FVIII ranged from 83 IU/kg bd– 107 IU/kg bd. 17 achieved complete success (undetectable inhibitor, normal FVIII pharmacokinetics), three partial success (undetectable inhibitor, abnormal pharmacokinetics). Inhibitor eradication failed in 3 pts. Median time to complete success was 1.8 years (range, 0.16–7.5). Conclusions: Data from this registry will provide additional information for a better understanding of predicting factors and supportive care initiatives that may influence ITI outcome. The registry will also allow comparison of the true costs of immune tolerance with non ITI treatment on a large European scale