Patients were randomized to receive FVIII regimens of either

50 IU kg−1 three times a week or 200 IU kg−1 daily. The study, which planned to enrol 150 patients, was prematurely terminated after 116 subjects had been randomized because of safety concerns. Specifically, children in the low-dose arm showed a significantly greater number of joint and non-joint Vincristine mouse bleeding episodes at all stages of ITI including prophylaxis after ITI termination, but particularly in the first ITI phase when inhibitors were still detectable [2]. At study termination, ITI success rates were not different in the two treatment arms, although therapeutic equivalence could not be proved due to insufficient statistical power. However, median time to achieve negative inhibitor titre and normal FVIII recovery were significantly shorter (about 50%) in patients who received the high-dose regimen [2]. These analyses also highlighted the need for homogeneous definitions of ITI

outcome. Clinical and laboratory criteria for assessing ITI outcome Seliciclib order adopted in the I-ITI study were established by consensus recommendations in 1999 and, more recently, were published [9]. The role of type of FVIII concentrate (plasma-derived vs. recombinant) also remains keenly debated. The issue was raised initially by German data highlighting a dramatic decline in the ITI success rate after introduction of monoclonal and recombinant FVIII learn more (rFVIII) products in ITI regimens, and the possibility of achieving

tolerance during ITI by switching from these products to plasma-derived FVIII (pdFVIII) products [10]. The presence of von Willebrand factor (VWF) in pdFVIII products has been advocated as an explanation for these findings due to the key role of VWF in FVIII function, stabilization and, possibly, immunogenicity [11]. However, data from the clinical literature indicate similarly high success rates in patients achieving tolerance with rFVIII concentrates, and thus far no prospective rigorous study is available [4]. Interestingly, a review of some case series of patients considered to have poor prognosis reported satisfactorily high ITI success rates with VWF-containing concentrates [11]. Some studies also suggested that testing for inhibitor epitope specificity and/or in vitro cross-reactivity towards different FVIII products might predict the individual response to ITI and support the choice for a specific type of FVIII concentrate. The RES.I.ST randomized trial was designed to provide a rigorous comparison in this setting; however, the study is currently ongoing only in ‘experienced’ patients, viz, prospective data are being collected in patients receiving VWF-containing concentrates after failure of a first ITI course with recombinant or monoclonal products [3].