Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: experience in the standard clinical setting.

The safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; Kogenate FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1-19 exposure days (EDs). Patients accumulated a mean (+/- SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical procedures, and the response to infusion was "excellent" or "good" in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0-19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

Immune tolerance induction with highly purified plasma-derived factor VIII containing von Willebrand factor in hemophilia A patients with high-responding inhibitors.

We retrospectively evaluated the efficacy of immune tolerance induction (ITI) in a homogenous cohort of eight patients with constitutive severe hemophilia A with high-responding factor VIII (FVIII) inhibitors using Facteur VIII-LFB/Factane, a highly purified FVIII concentrate containing von Willebrand factor (VWF).

Cost-of-illness study of severe haemophilia A and B in five French haemophilia treatment centres.

OBJECTIVE: The aim of this study was to assess the consumption of anti-haemophilic drugs by adults and children with severe haemophilia A or B (residual activity of FVIII or FIX < or =2%) and to quantify the average direct medical costs. METHOD: A retrospective multicentre cost-of-illness study from the perspective of French national health insurance system. The costs include only the use of clotting factors. MAIN OUTCOME MEASURE: Consumption was expressed in UI/kg/year and costs in euros/kg/year. RESULTS: From January 1, 2001 to December 31, 2002, data from 81 adults and 30 children with severe haemophilia A (n = 92) or B (n = 19) and included in the "SNH" were collected and analysed. A coagulation factor inhibitor was present in 10 patients (9%). Four of them were high responders. Mean age and body weight were respectively 28 +/- 17 years and 58 +/- 24 kg. Except for one adult patient, all (99%) had outpatient treatment, 44 patients (40%) were hospitalized and treated by recombinant or/and plasma-derived FVIII or FIX or/and rFVIIa. Overall median annual consumption of anti-haemophilic drugs per patient was estimated at 1,333 UI/kg, with a median cost-of-illness of 1,156 euros/kg. Patients with severe haemophilia B consumed more than patients with severe haemophilia A, though not significantly (P = 0.096), with a median of 2,167 vs. 1,100 UI/kg/year and a median cost of 1,760 vs. 917 euros/kg/year (P = 0.13). Children consumed respectively more than adults (P = 0.008), with a median of 3,204 vs. 1,106 UI/kg/year and a median cost of 2,614 vs. 913 euros/kg/year (P = 0.012). The median cost for patients with an inhibitor was 3,291 euros/kg/year, approximately threefold higher than that of patients without an inhibitor (926 euros/kg/year) (P = 0.022). CONCLUSION: It suggests a higher consumption and cost of anti-haemophilic drugs among children when compared to adults. Haemophilia B patients did not consume significantly more than haemophilia A patients, whereas the consumption and cost for patients with or without inhibitors differed significantly.

Prevalence of IgG antibodies to human parvovirus B19 in haemophilia children treated with recombinant factor (F)VIII only or with at least one plasma-derived FVIII or FIX concentrate: results from the French haemophilia cohort.

Human parvovirus B19 (B19) has been transmitted by some brands of virally attenuated plasma-derived factor VIII (FVIII) or IX (FIX) concentrates. To quantify the differences of human parvovirus B19 risk transmission between albumin-stabilized recombinant factor and plasma-derived factor, we studied the prevalence of IgG antibodies to B19 (anti-B19) in 193 haemophiliac children between 1 and 6-years of age who had previously been treated with albumin-stabilized recombinant FVIII only (n = 104), and in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates (n = 89). Association between the prevalence of anti-B19 and the treatment group was analysed using multivariate logistic regression. Age, severity and type of haemophilia, number of cumulative days of exposure to factor VIII or IX, previous history of red blood cells or plasma transfusion were considered as potential confounding variables. A higher prevalence of anti-B19 was found in children previously treated with solvent/detergent high-purity non-immunopurified and non-nanofiltered FVIII or IX concentrates than in children treated with albumin- stabilized recombinant FVIII only (OR: 22.3; CI: 7.9-62.8), independently of the other factors studied.