Yazarlar : Lars Jorgensen

Yayın : DGNews

Yayın Yılı : 2014

Pubmed Linki : http://www.docguide.com/recombinant-factor-viii-prophylaxis-reduces-bleeding-children-haemophilia?tsid=5

Konu : Hemofili

Literatür İçeriği :  MILAN, Italy -- June 17, 2014 -- Infusions of long-acting recombinant factor VIII Fc-fusion protein (rFVIIIFc) demonstrate safety and efficacy in the treatment and reduction of bleeding episodes in young patients with severe haemophilia A, according to results from a phase 3 study presented here at the 19th Congress of the European Hematology Association (EHA).

Standard prophylactic factor VIII (FVIII) therapy is recommended to prevent bleeding and potential joint disease in severe haemophilia. However, some reports have shown the treatment to have a shorter half-life in children than in adults, requiring even more frequent dosing than the standard regimen.

A previous study of rFVIIIFc showed an increased half-life compared with standard FVIII in adolescents and adults with infusions of once or twice a week, stated lead author Guy Young, MD, University of California-Los Angeles, Los Angeles, California, on June 14.

Dr. Young and colleagues evaluated rFVIIIFc in previously treated paediatric patients in an open-label, multi-centre study dubbed Kids-A-LONG, which included 71 boys under the age of 12 years (including 36 children between 1 and 5 years) with severe haemophilia.

In all, 89% of patients received a prestudy FVIII prophylaxis regimen; 74.6% of them required ≥3 infusions per week. The researchers noted that “rFVIIIFc offers the potential of prolonged dosing intervals and fewer infusions for paediatric patients with severe haemophilia A.”

Patients were initially treated in the new study with twice-weekly prophylactic infusions of rFVIIIFc (25 IU/kg day 1, 50 IU/kg day 4), with dosing frequency increased as needed to as often as once every 2 days. The dose could also be increased to up to 80 IU/kg, as determined by the investigator.

With a median time in the study of 26 weeks, 61 of the patients had ≥50 days of exposure to rFVIIIFc. The median average weekly dose was 88.1 IU/kg, and the average dosing interval was 3.5 days.

Among the 94.4% of patients who completed the study, none developed inhibitors to the drug.

The mean terminal half-life in patients aged <6 years and between 6 and 12 years was 12.67 hours (95% confidence interval [CI], 11.23-14.11) and 14.88 hours (95% CI, 11.98-17.77), respectively, representing an increase over FVIII therapy that was similar to the 1.5-fold increase in half-life seen in the previous study of adults and adolescents.

The patients’ overall median annualised bleeding rate was 1.96 (interquartile range [IQR], 0.00-3.96), and the rate for spontaneous bleeds was 0.00.

Most (93.0%) bleeding episodes were controlled with 1 or 2 infusions, with a median dose per bleeding episode of 54.9 IU/kg.

“The increase in half-life compared with current FVIII and the safety profile were generally consistent with [those] observed in the phase 3 study in adults and adolescents,” the researchers concluded.

[Presentation title: Kids A-Long: Safety, Efficacy, and Pharmacokinetics of Long-Acting Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Paediatric Subjects With Haemophilia A. Abstract LB-6204]

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