Efficacy and safety of secondary prophylactic vs. on‐demand sucrose‐formulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13‐month crossover study

Abstract

To cite this article: Collins P, Faradji A, Morfini M, Enriquez MM, Schwartz L. Efficacy and safety of secondary prophylactic vs. on-demand sucroseformulated recombinant factor VIII treatment in adults with severe hemophilia A: results from a 13-month crossover study. J Thromb Haemost 2010; 8: 83-9.See also Aledort LM. To bleed or not to bleed -is that a question. This issue, pp 81-2.Summary. Background: Hemarthroses in severe hemophilia precipitate physical, psychosocial and financial difficulties. Objective: To compare the effects of secondary prophylaxis with on-demand sucrose-formulated recombinant factor VIII (rFVIII-FS) therapy in severe hemophilia A. Patients and methods: This open-label study included patients aged 30-45 years with factor VIII (FVIII) coagulant activity < 1 IU dL )1 who were using on-demand FVIII treatment.Patients were treated with rFVIII-FS on demand for 6 months, followed by 7 months prophylaxis (20-40 IU kg, three times per week, with the first month considered a run-in). The primary endpoint was the number of hemarthroses. Results: Twenty patients were enrolled (n = 19 completed); the mean age was 36.4 years, and 16 had target joints. The median (25-75%) number of joint bleeds decreased significantly with prophylaxis [0 (0-3)] vs. on-demand [15 (11-26); P < 0.001] therapy. The number of all bleeds was 0 (0-3) vs. 20.5 (14-37; P < 0.001), respectively. Median (range) total Gilbert scores improved after prophylaxis [18 (3-39)] compared with on-demand [25 (4-46)] therapy, predominantly reflecting the improved bleeding score. Median time from last prophylactic infusion to bleed was 2 days; 82.5% of bleeds occurred 2-3 days after the last infusion. Median 48-h and 72-h FVIII trough levels measured during months 10 and 13 were consistently > 6 and > 4 IU dL )1 , respectively. Treatment was well tolerated, and no inhibitor formation was observed. Conclusion: Secondary prophylaxis with rFVIII-FS significantly reduced the frequency of hemarthroses compared with on-demand therapy in adult patients with severe hemophilia A.

Prophylaxis usage, bleeding rates, and joint outcomes of hemophilia, 1999 to 2010: a surveillance project

“…5 Randomized clinical data on the efficacy of prophylaxis to prevent bleeding and improve joint function has been more recently reported in adolescents and adults. [16][17][18] Data from the CDC/USHTCN surveillance registry of over 6000 individuals shows that prophylaxis treatment increased from 31% overall in 1999 to 59% in 2010, including 75% of all children and adolescents. During the same time, joint and total hemorrhages were markedly reduced.…”

Enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX: a first human dose trial in patients with hemophilia B

“…16 N9-GP is a recombinant serum-free hemostatic protein that has been modified to prolong the t [1/2] . This is achieved by site-directed glycoPEGylation that makes it possible to attach a 40-kDa polyethylene glycol (PEG) molecule to the FIX activation peptide.…”

Implications of coagulation factor VIII and IX pharmacokinetics in the prophylactic treatment of haemophilia

“…One prospective study [42] of 19 evaluable patients has shown that patients with severe haemophilia A (FVIII < 1 IU dL )1 ) and a median age of 36 years, 80% of whom had target joints at study entry, treated with 25 IU kg )1 3 days a week, had a median of 0 bleeds in 6 months compared with a median of 21 bleeds while receiving on-demand treatment. The median (inter-quartile range) FVIII trough levels measured at 48 and 72 h in these patients were 6 (1-11) and 4 (0.5-6) IU dL , respectively.…”