Randomized, controlled, parallel‐group trial of routine prophylaxis vs. on‐demand treatment with sucrose‐formulated recombinant factor VIII in adults with severe hemophilia A ( SPINART )

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 (r FVIII ‐ 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 r FVIII ‐ 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 P  < 0.0001). No treatment‐related adverse events occurred, and no patients developed FVIII inhibitors. Conclusions Routine prophylaxis with r FVIII ‐ FS leads to a significant reduction in bleeding as compared with on‐demand treatment. Adverse events were consistent with the established r FVIII ‐ FS safety profile.