High-titre inhibitors in previously untreated patients with severe haemophilia A receiving recombinant or plasma-derived factor VIII: a budget-impact analysis.

The SIPPET (Survey of Inhibitors in Plasma-Products Exposed Toddlers) trial1 provided evidence that, in previously untreated patients with severe haemophilia A, recombinant factor VIII increases the risk of developing high-titre inhibitors as compared with plasma-derived factor VIII. This multicentre, international study enrolled 264 previously untreated patients (mean age, around 20 months) who were randomised to receive either recombinant factor VIII or plasma-derived factor VIII. Inhibitors developed in 29/125 patients treated with plasma-derived factor VIII (high-titre inhibitors: 20 patients) and in 47/126 patients treated with recombinant factor VIII (high-titre inhibitors: 30 patients). The cumulative rates of all inhibitors were 26.8% with plasma-derived factor VIII (high-titre inhibitors: 18.6%; 95% confidence interval [CI]: 11.2 to 26.0) and 44.5% with recombinant factor VIII (high-titre inhibitors: 28.4%; 95% CI: 19.6 to 37.2). This implies that, in the SIPPET trial, the relative risk reduction for the incidence of high-titre inhibitors was 34.5% for plasma-derived factor VIII compared with recombinant products. All inhibitors occurred before 39 exposure days; all high-titre inhibitors occurred before 34 exposure days (median: 7 to 8 exposure days). These findings have important clinical implications, but their budget impact also deserves to be considered, particularly because of the high cost incurred in the treatment of high-titre inhibitors. In November 2015, we published a preliminary assessment on this topic based on the initial results of SIPPET and on a simple narrative analysis2. To address this issue better, in the present study we developed a Markov model and studied the economic consequences in terms of budget impact that, in previously untreated patients with severe haemophilia A, can derive from using plasma-derived products as opposed to recombinant factor VIII.