83 (95% CI: 0.46–1.52) for pooled FL-rFVIII and BDD-rFVIII; 0.42 (0.19–0.93) for pooled FL-rFVIII; and 2.61 (1.21–5.53) for pooled BDD-rFVIII (Fig. 1). Once again, however, the generalisability of the results of this meta-analysis is limited by the quality of the Tamoxifen mw studies available for inclusion. The actual number of patients with inhibitors was small (35 in total) and the confidence interval for the pooled BDD-rFVIII result was particularly large. Such limitations introduce the possibility of type 1 error when interpreting the findings. Perhaps the main message to emerge from this meta-analysis is that the incidence of de novo inhibitors in PTPs receiving any rFVIII concentrate (either

full length or B-domain deleted) is about 1%, which is substantiated by the narrow confidence interval (0.46–1.52) and is similar to that reported in other analyses. However, whether a real difference exists between full-length and BDD-rFVIII continues to remain uncertain FK506 [12]. At present, clotting factor therapy is relatively inconvenient because prophylaxis is done on a large scale and tends to involve repeated intravenous infusions, generally 2–3 times weekly or even daily by patient choice. On the other hand, there is a genuine need to consider the various challenges to innovation of haemophilia treatment as patient satisfaction with the current range of products is already quite high.

On this note, clinical trial protocols prescribed by regulatory agencies are becoming increasingly demanding which presents a very real obstacle to the design and conduct of randomized, controlled trials – especially within the context of a rare disorder such as haemophilia B – and in light of the high costs associated with conducting clinical trials. The potential also exists for neo-antigenicity to emerge as a result of molecular manipulation

which often comes to light only once the product has passed through clinical trial stage and is used in the wider population. check details The current range of FVIII products has an approximate plasma half-life of 10–12 h (longer for FIX) which underlies the need for repeated infusions. As such, it is not surprising that approaches to prolong its half-life have been leading attempts to improve factor replacement therapy for patients with haemophilia. The potential benefits of longer-acting factors include extended protection from bleeding, reduced infusion frequency, and the possibility of avoiding a central catheter for venous access and its attendant issues. The first approach attempted to prolong plasma half-life was to attach FVIII to a ‘sustained-release’ delivery vehicle (e.g. liposomes), but this proved unsuccessful and has since been abandoned. Current approaches under investigation involve hydrophilic polymer conjugation (e.g. PEGylation) and variant protein generation (e.g. fusion factors).