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

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(-1), 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.