60). The reported P value for this difference is 0.02; however, different statistical assumptions apply when analysing post hoc-derived data, so that this P value does not prove a non-casual difference, although to the physician who is untrained in the nuances of biostatistics, the P value may appear to have the usual meaning of clinical significance [4]. There was no biologically plausible
www.selleckchem.com/products/BKM-120.html explanation for this last finding and a previous publication using the second-generation BHK-synthesized rFVIII concentrate in PUPs would refute this finding [5]. In any case, it may be a moot point since a third-generation formulation of the BHK derived full-length rFVIII concentrate is expected to be commercially available shortly. This new BHK product will match the purity, specific activity and degree of freedom from synthesis and purification in the presence of added human protein as the currently available third-generation FVIII concentrate derived from CHO cells. Nevertheless, several speculations have arisen as to the aetiology of the differential immunogenicity of the second and third-generation products. For instance, the BHK formulation may contain
more FVIII protein in aggregate form [6], which could affect enhanced antigen processing by the antigen presenting cells of the immune system with subsequent peptide formation; alternatively, the two different cell lines Saracatinib concentration could generate rFVIII proteins with different degrees of glycosylation and the immune system might process these two proteins differently. It should be noted, in this context, that a similar increased
risk for inhibitor development, even if not reaching statistical significance, was demonstrated in PTPs in a recent published and widely discussed meta-analysis (HR for all de novo inhibitors 2.43; CI, 0.31–19.2 and HR for high-titre de novo inhibitors ZD1839 supplier 1.75; CI, 0.05–65.5, for BHK vs. CHO) [7]. Those who read this commentary understand how difficult it is to conduct randomized controlled clinical trials in the haemophilia arena. Although one of the largest and more comprehensive prospective studies to date, the Rodin study does not provide such a high level of evidence to allow a strong confidence in its results. The authors are the first ones to state that their study has important limitations. For instance, Rodin is not a fully prospective controlled study and was predominantly comprised of a lower risk ethnic population (90% Caucasians) for inhibitor development.