Efficacy assessment of a new clotting factor concentrate in haemophilia A patients, including prophylactic treatment

Abstract

Currently, efficacy of a new factor concentrate is mostly judged by its ability to achieve haemostasis after a bleeding episode. However, in patients on prophylaxis, the effectiveness in preventing bleeds, and thus joint damage, is most important. An albumin-free recombinant factor VIII (FVIII) concentrate was introduced in the Netherlands in 2004. In this study, the efficacy of a new recombinant plasma/albumin-free FVIII concentrate (rAHF-PFM, Advate) was assessed by comparing bleeding frequency and factor consumption before and after switching to the new product, on both prophylactic and on-demand treatment. Eighty-two previously treated haemophilia A patients with at least 1-year clinical follow-up were included in this study. Data on 410 patient-years were analysed, including 165 patient-years on other clotting factor products, and 245 patient-years on the new concentrate. In total, 19 628 368 IU of other factor concentrates were administered, to treat 839 bleeds, including 578 joint bleeds and cover 104 years of prophylactic treatment. For rAHF-PFM 33 082 250 IU FVIII, were used to treat 1144 bleeds, including 734 joint bleeds and cover 175 years of prophylactic treatment. No inhibitors, seroconversions or other serious adverse events were observed. Annual FVIII consumption per kg and annual number of joint bleeds before and after switching to the new albumin-free recombinant factor concentrate were similar in all patients. In conclusion, rAHF-PFM is equally effective as other clotting factor concentrates for prophylactic treatment in severe haemophilia.

Can B‐domain deletion alter the immunogenicity of recombinant factor VIII? A meta‐analysis of prospective clinical studies

“…Twenty‐nine prospective clinical studies reported from 1990 to 2010 with 3012 total patients at risk for de novo inhibitor development were included in the meta‐analysis [10,14–16,32–60]. All were published.…”

Integrated analysis of safety data from 12 clinical interventional studies of plasma‐ and albumin‐free recombinant factor VIII (rAHF‐PFM) in haemophilia A

“…In most countries (including the United States since 2011), rAHF‐PFM is also indicated for prophylaxis to prevent or reduce bleeding. Early studies confirmed the efficacy of rAHF‐PFM . Iorio et al .…”

Phenotypic heterogeneity and evidence of a founder effect associated with G6PC3 mutations in patients with severe congenital neutropenia

“…It should be noted that this was an open label trial and was not randomized or blinded. A similar design was used in a clinical trial comparing the efficacy of a new FVIII concentrate (Advate) to that of previous treatment documented in the clinic's registry (Den Uijl et al, 2009). Nevertheless, additional data from a larger randomized and blinded clinical trial would be valuable to firmly support the findings of the current study.…”