Personalized Prophylaxis with Human-Cl Recombinant FVIII in HA Patients
Blood(2015)
Abstract
Abstract Background Prophylactic therapy aims to maintain sufficient factor VIII (FVIII) plasma levels to prevent bleeding. FVIII plasma trough level and time spent above a certain threshold are mainly determined by the half-life of the FVIII concentrate and the injection interval. Aims A clinical study was conducted to investigate the efficacy of individually PK-tailored prophylaxis with Human-cl rhFVIII. Methods This prospective, open-label, multicenter phase 3b study included previously treated immunocompetent adult patients with severe hemophilia A without past or present inhibitors. Each patient started with a PK evaluation (single dose of 60 ± 5 IU/kg) followed by 1-3 months of routine prophylaxis (i.e. 30-40 IU/kg every other day or 3 times per week, Phase I) until individual PK data was analyzed. It was calculated, which dose and injection interval would theoretically result in a trough FVIII level of ≥1%. Then, prophylaxis was continued for 6 months using the individually recommended treatment scheme (Phase II). Results The study enrolled 66 patents from 20 centers across 8 countries. The majority of patients (62.1%) had been treated on-demand only before study entry. Their median annualized bleeding rate (ABR) was 41. Key outcomes of the personalized prophylaxis are: The prophylactic injection interval was extended from usually 3 times per week in Phase-I to twice per week or less in 58% of patients.The median dosing interval was 3.5 days.73% of patients did not experience any bleeding episode.The mean ABR in phase-II was 1.45 (3.16 in Phase-I).The median weekly prophylactic dose decreased by nearly 10% compared to Phase-I.There were no inhibitors and related serious adverse events. Conclusion The data suggest that personalized prophylaxis with Human-cl rhFVIII results in a more convenient treatment for more than half of the patients with lower factor consumption and a lower ABR while remaining safe and efficacious. Disclosures Klamroth: Biogen and SOBI: Honoraria, Speakers Bureau; Bayer, Baxter, CSL Behring, Pfizer, Novo Nordisk, and Octapharma: Honoraria, Research Funding, Speakers Bureau. Rusen:Octapharma: Other: Investigator. Walter:Octapharma: Employment. Bichler:Octapharma AG: Employment. Pasi:Biogen, Octapharma, Genzyme, and Pfizer: Consultancy, Honoraria; Octapharma: Research Funding. Tiede:Octapharma: Other: Investigator, Speakers Bureau; Leo Pharma: Consultancy, Honoraria; SOBI: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria, Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Biogen Idec: Consultancy, Honoraria; Biotest: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Honoraria, Investigator, Research Funding; Baxter: Consultancy, Honoraria, Research Funding; Coachrom: Research Funding. Knaub:Octapharma: Employment.
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