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Clinical Trial
. 2012 Jun;107(6):1072-82.
doi: 10.1160/TH11-09-0642. Epub 2012 Apr 4.

Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A

Guenter Auerswald  1 , Alexis A Thompson, Michael Recht, Deborah Brown, Raina Liesner, Norma Guzmán-Becerra, Jacqueline Dyck-Jones, Bruce Ewenstein, Brigitt Abbuehl
Affiliations
Clinical Trial

Experience of Advate rAHF-PFM in previously untreated patients and minimally treated patients with haemophilia A

Guenter Auerswald et al. Thromb Haemost. 2012 Jun.

Abstract

We report a prospective trial of 55 previously untreated patients (PUPs) and minimally treated patients (MTPs) with severe/moderately severe haemophilia A (baseline factor VIII [FVIII] ≤2%) treated with a single FVIII replacement product. It was the objective of this study to evaluate the immunogenicity, efficacy, and safety of rAHF-PFM (Advate®). On-demand or prophylactic treatment regimens were determined at the discretion of the investigator. rAHF-PFM was also permitted for perioperative management. There were 633 bleeding episodes (BEs), including 517 treated, and 466 rated for efficacy. Haemostatic efficacy was considered excellent/good in 93% of 466 rated treatments. Of 517 treated BEs, 463/517 (90%) were managed with one (356/517 [69%]) or two infusions (107/517 [21%]). There were 27 surgeries. Intraoperative (n=22) and postoperative (n=25) haemostatic efficacies were considered excellent or good in 100% of rated surgeries. Related serious adverse events (SAEs) were inhibitor development in 16/55 (29.1%) subjects who received at least one infusion of rAHF-PFM. Non-serious, related adverse events (AEs) were few in number (14 in eight subjects). The odds ratio (OR [95% Confidence Interval, CI]) of developing inhibitors was significantly higher in subjects with a family history of inhibitor (4.95[1.29-19.06]), non-Caucasian ethnicity (4.18, [1.18-14.82]), and intensive treatment at high dose (4.5 [1.05-19.25]) within ≤20 exposure days (EDs). In conclusion, rAHF-PFM was safe and effective for the management and perioperative coverage of PUPs/MTPs with severe/moderately severe haemophilia A. This report supports previous findings from studies in which family history of inhibitor, non-Caucasian ethnicity, and high intensity treatment were associated with high risk of inhibitor development.

Trial registration: ClinicalTrials.gov NCT00157157.

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Conflict of interest statement

Conflicts of interest The work presented is a Baxter-sponsored clinical study. Several authors (N. Guzmán-Becerra, J. A. Dyck-Jones, B. M. Ewenstein, and B. E. Abbuehl) are employed by Baxter Healthcare, Inc. G. Auerswald, A. A. Thompson, M. Recht, D. Brown, and R. Liesner were investigators in the study and therefore their institutions received research support from Baxter Healthcare, Inc. In addition, G. Auerswald received grants for symposia or clinical studies and congresses from Baxter, Bayer, CSL-Behring, Novo Nordisk and Biotest. M. Recht also received institutional research support from Novo Nordisk and Biogen Idec, and R. Liesner previously received payment from Baxter for consultancies and honoraria.

Figures

Figure 1: Disposition of subjects (A) and distribution of bleeding episodes (B)
Figure 1: Disposition of subjects (A) and distribution of bleeding episodes (B)
. BE=bleeding episodes, Hgb=haemoglobin, n=number of subjects. a Of the 55 subjects dosed, 44 subjects received treatment for at least one BE and the remaining 11 subjects received rAHF-PFM for other reasons (e.g. recovery study infusion, surgical prophylaxis, prophylactic regimen, etc.) One subject did not meet eligibility criteria but was inadvertently dosed and subsequently withdrawn.
Figure 2: Cumulative incidence of inhibitor development
Figure 2: Cumulative incidence of inhibitor development
See this image and copyright information in PMC

References

    1. Tarantino MD, Collins PW, Hay CR et al.Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A. Haemophilia. 2004;10:428–437. - PubMed
    1. Blanchette VS, Shapiro AD, Liesner RJ et al.Plasma and albumin free recombinant factor VIII (rAHF-PFM): pharmacokinetics, efficacy and safety in previously treated pediatric patients. J Thromb Haemost. 2008;6:1319–1326. - PubMed
    1. Negrier C, Shapiro A, Berntorp E et al.Surgical evaluation of a recombinant Factor VIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients. Thromb Haemost. 2008;100:217–223. - PubMed
    1. Franchini M, Tagliaferri A, Mengoli C et al.Cumulative inhibitor incidence in previously untreated patients with severe hemophilia A treated with plasma-derived versus recombinant factor VIII concentrates: A critical systematic review. Crit Rev Oncol Hematol. 2012;81:82–93. - PubMed
    1. Iorio A, Halimeh S, Holzhauer S et al.Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: a systematic review. J Thromb Haemost. 2010;8:1256–1265. - PubMed

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