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)

Abstract

To cite this article: Manco-Johnson MJ, Kempton CL, Reding MT, Lissitchkov T, Goranov S, Gercheva L, Rusen L, Ghinea M, Uscatescu V, Rescia V, Hong W. 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). J Thromb Haemost 2013; 11: 1119-27.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 sucroseformulated 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 À1 , 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 treatmentrelated 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.

Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A

“…The median ABR in the individualized prophylaxis arm was consistent with ABRs reported for other prophylactic regimens, [15][16][17] and 45.3% of subjects experienced no bleeding episodes on study. The majority of subjects *The median dosing interval among subjects on study for at least 6 months was 3.5 (range, 2.9-5.7) days when averaged over all dosing intervals during the respective time intervals for the last 3 months on the study.…”

“…For subjects randomized to arm 2, there was a statistically significant reduction in ABR relative to their prior episodic regimen, and most subjects achieved an ABR in the range reported for existing prophylactic regimens. [15][16][17] The low median ABR and observation that some subjects (4/23, 17.4%) had no breakthrough bleeding episodes indicate that once-weekly prophylaxis can provide positive clinical outcomes for some patients. However, 3 subjects (13.0%) in this arm experienced .5 bleeding episodes on the study.…”

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

“…5 To date, clinical trial evidence supports the efficacy of initiation of prophylaxis after exceeding these thresholds in reducing the rate of joint hemorrhage in adolescents and adults with preexisting arthropathy, but has not provided definitive data on joint outcomes other than bleeding in patients beyond early childhood. 6,7 Factors previously determined to predict joint disease and poor physical function in boys with hemophilia include joint hemorrhage, increasing age, obesity, African American race, and inhibitor formation. [8][9][10] In 1997, the Centers for Disease Control and Prevention (CDC) in collaboration with the US Hemophilia Treatment Center Network (USHTCN), a specialty health care network primarily housed in academic centers, initiated a prospective surveillance system called the Universal Data Collection (UDC) system for outcomes of hemophilia, directed and funded by a US Congressional mandate, with a goal of developing preventive strategies; the structure, organization, and participants of the UDC have been previously described.…”

Registry‐based outcome assessment in haemophilia: a scoping study to explore the available evidence

“…Results from such studies were published more recently [6,10] and facilitated the introduction of prophylaxis as the best practice in children with severe haemophilia. Later, similar studies demonstrated the benefit of prophylaxis for adult patients [11].…”