PMID- 22476554
OWN - NLM
STAT- MEDLINE
DCOM- 20121016
LR  - 20211203
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 107
IP  - 6
DP  - 2012 Jun
TI  - Experience of Advate rAHF-PFM in previously untreated patients and minimally 
      treated patients with haemophilia A.
PG  - 1072-82
LID - 10.1160/TH11-09-0642 [doi]
AB  - 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(R)). 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.
FAU - Auerswald, Guenter
AU  - Auerswald G
AD  - Prof.-Hess-Kinderklinik, Klinikum Bremen-Mitte, St.-Juergen Str. 1, 28177 Bremen, 
      Germany. guenterauerswald@aol.com
FAU - Thompson, Alexis A
AU  - Thompson AA
FAU - Recht, Michael
AU  - Recht M
FAU - Brown, Deborah
AU  - Brown D
FAU - Liesner, Raina
AU  - Liesner R
FAU - Guzman-Becerra, Norma
AU  - Guzman-Becerra N
FAU - Dyck-Jones, Jacqueline
AU  - Dyck-Jones J
FAU - Ewenstein, Bruce
AU  - Ewenstein B
FAU - Abbuehl, Brigitt
AU  - Abbuehl B
LA  - eng
SI  - ClinicalTrials.gov/NCT00157157
PT  - Clinical Trial
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20120404
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies)
RN  - 0 (Hemostatics)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Antibodies/blood
MH  - Drug Administration Schedule
MH  - Ethnicity
MH  - Europe/epidemiology
MH  - Factor VIII/administration & dosage/adverse effects/immunology/*therapeutic use
MH  - Female
MH  - Hemophilia A/blood/complications/*drug therapy/ethnology
MH  - Hemorrhage/blood/*drug therapy/ethnology/etiology
MH  - Hemostasis/*drug effects
MH  - Hemostatics/administration & dosage/adverse effects/immunology/*therapeutic use
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Linear Models
MH  - Logistic Models
MH  - Male
MH  - North America/epidemiology
MH  - Odds Ratio
MH  - Prospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC6292131
COIS- Conflicts of interest The work presented is a Baxter-sponsored clinical study. 
      Several authors (N. Guzman-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.
EDAT- 2012/04/06 06:00
MHDA- 2012/10/17 06:00
PMCR- 2018/12/13
CRDT- 2012/04/06 06:00
PHST- 2011/09/15 00:00 [received]
PHST- 2012/03/10 00:00 [accepted]
PHST- 2012/04/06 06:00 [entrez]
PHST- 2012/04/06 06:00 [pubmed]
PHST- 2012/10/17 06:00 [medline]
PHST- 2018/12/13 00:00 [pmc-release]
AID - 11-09-0642 [pii]
AID - 10.1160/TH11-09-0642 [doi]
PST - ppublish
SO  - Thromb Haemost. 2012 Jun;107(6):1072-82. doi: 10.1160/TH11-09-0642. Epub 2012 Apr 
      4.