Integrated analysis of safety and efficacy of a plasma- and albumin-free recombinant factor VIII (rAHF-PFM) from six clinical studies in patients with hemophilia A

Abstract

Background: Hemophilia A is an X-linked bleeding disorder that results from insufficient levels of factor VIII (FVIII) coagulant activity. Objective: To evaluate the efficacy and safety of ADVATE^® rAHF–PFM (Baxter Healthcare Corporation), a recombinant FVIII concentrate manufactured without human or bovine blood-derived additives, and to assess the effect of compliance with prophylactic use in preventing bleeding episodes (BEs). Methods: Clinical data were integrated from six prospective studies. Two hundred thirty-four hemophilia A subjects (FVIII levels ≤ 2%) (median age 14.7 (range: 0.02 – 72.7) years) were included. Results: BEs were managed with one or two infusions and nearly all (1953/1956) responded to treatment. Compliance with a prophylactic treatment regimen significantly reduced the incidence of BEs (p = 0.0061) and prevented non-traumatic joint BEs (median annualized BE rate was 0). One previously treated subject developed an inhibitor; no other safety concerns were observed. Conclusions: These results reinforce the efficacy and safety of rAHF-PFM and suggest that compliance is an essential contributor to the effectiveness of prophylaxis in the treatment of hemophilia A.

Keywords::

• efficacy
• factor VIII
• hemophilia A
• prophylaxis
• rAHF-PFM
• safety

Acknowledgements

The authors would like to recognize the investigators who participated in these studies that were conducted in their respective countries: T Abshire, MD (Atlanta, GA), C Altisent, MD (Barcelona, Spain), A Angiolillo, MD (Washington, DC), S Arkin (New Hyde Park, NY), G Auerswald, MD (Bremen, Germany), D Becton, MD (Little Rock, AR), E Berntorp, MD, PhD (Malmo, Sweeden), V Blanchette, MD (Ontario, Canada), HH Brackmann, MD (Bonn, Germany), D Brown, MD (Chicago, IL), H Chambost, MD (Marseille, France), P Collins, MD (Cardiff, United Kingdom), J DiPaola, MD (Iowa City, IA), B Ewenstein, MD, PhD (Boston, MA), D DiMichele, MD (New York, NY), A Dunn, MD (Atlanta, GA), K Fukutake, MD (Tokyo, Japan), P Giangrande, MD (Oxford, United Kingdom), J Gill, MD (Milwaukee, WI), A Gringeri, MD (Milano, Italy), R Gruppo, MD (Cincinnati, OH), H Hanabusa, MD (Suginami-ku, Japan), Y Hatae, MD (Hokkaido, Japan), CRM Hay, MD (Manchester, United Kingdom), F Hernandez, MD (Madrid, Spain), K Hoots, MD (Houston, TX), AM Hurlet-Jensen, MD (New York, NY), J Ingerslev, MD (Aarhus, Denmark), E Kakishita, MD (Hyogo, Japan), W Kreuz, MD (Frankfurt, Germany), R Kulkarni, MD (East Lansing, MI), M Kurth, MD (Minneapolis, MN), T Lambert, MD (Bicetre, France), C Leissinger, MD (New Orleans, LA), C Lee, MD (London, United Kingdom), R Liesner, MD (London, United Kingdom), C Male, MD (Vienna, Austria), M Manco-Johnson, MD (Aurora, CO), C Manno, MD (Philadelphia, PA), PM Mannucci, MD (Milano, Italy), PW Marks, MD, PhD (Boston, MA), J Mimaya, MD (Shizuoka, Japan), C Negrier, MD (Lyon, France), R Nuss, MD (Aurora, CO), I Ortiz, MD (San Juan, Puerto Rico), I Pabinger, MD (Vienna, Austria), P Petrini, MD (Stockholm, Sweden), C Philipp, MD (Bew Brunswick, NJ), S Pipe, MD (Ann Arbor, MI), H Pollmann, MD (Munster, Germany), MV Ragni MD (Pittsburgh, PA), M Recht, MD (Phoenix, AZ), B Ritchie, MD (Alberta, Canada), C Rothschild, MD (Paris, France), H Sakai, MD (Miyagi, Japan), I Scharrer, MD (Frankfurt, Germany), F Shafer, MD (Philadelphia, PA), A Shapiro, MD (Indianapolis, IN), M Shima, MD (Nara, Japan), A Shirahata MD (Fukuoka, Japan), M Siimes, MD (Helsinki, Finland), J Takamatsu, MD (Aichi, Japan), M Taki, MD (Kanagawa, Japan), M Tarantino, MD (Peoria, IL), A Thompson, MD (Chicago, IL), A Thompson, D (Seattle, WA), M Trossaert, MD (Nantes, France), M van den Berg, MD (Utrecht, Netherlands), J Vermylen, MD (Leuven, Belgium), I Walker, MD (Ontario, Canada), I Warrier, MD (Detroit, MI), C Wermes, MD (Hannover, Germany), and WY Wong, MD (Los Angeles, CA).

The following Baxter employees made significant contributions to the manuscript: N Guzman-Becerra, and G Spotts. Four of the six studies described in this report are registered: NCT00157053, NCT00157040, NCT00157105 and NTC00157157; two studies were conducted prior to the registration requirement.

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