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Keywords:

  • hemophilia A;
  • on demand;
  • prophylaxis;
  • sucrose-formulated recombinant factor VIII

Summary

Background

The benefits of routine prophylaxis vs. on-demand treatment with factor VIII products have not been evaluated in controlled clinical trials in older patients with hemophilia A.

Objectives

To report results from a preplanned analysis of data from the first year of the 3-year SPINART study, which compares routine prophylaxis with on-demand treatment with sucrose-formulated recombinant FVIII (rFVIII-FS).

Patients/Methods

SPINART is an open-label, randomized, controlled, parallel-group, multinational trial. Males aged 12–50 years with severe hemophilia A, ≥ 150 days of exposure to FVIII, no FVIII inhibitors, no prophylaxis for > 12 consecutive months in the past 5 years and 6–24 bleeding episodes in the preceding 6 months were randomized 1 : 1 to rFVIII-FS prophylaxis (25 IU kg−1, three times weekly) or on-demand treatment. The primary efficacy endpoint, number of total bleeding episodes in the intent-to-treat population, was analyzed after the last patient had completed 1 year of follow-up. A negative binomial model was used for the primary endpoint analysis; analysis of variance was used for confirmatory analysis of annualized bleeding rates.

Results

Eighty-four patients were enrolled and analyzed (n = 42 per group; mean age, 30.6 years; median treatment duration, 1.7 years). The median number of total bleeding episodes and total bleeding episodes per year were significantly lower with prophylaxis than with on-demand treatment (total, 0 vs. 54.5; total per year, 0 vs. 27.9; both < 0.0001). No treatment-related adverse events occurred, and no patients developed FVIII inhibitors.

Conclusions

Routine prophylaxis with rFVIII-FS leads to a significant reduction in bleeding as compared with on-demand treatment. Adverse events were consistent with the established rFVIII-FS safety profile.