PMID- 26010678
OWN - NLM
STAT- MEDLINE
DCOM- 20160809
LR  - 20151023
IS  - 1365-2516 (Electronic)
IS  - 1351-8216 (Linking)
VI  - 21
IP  - 6
DP  - 2015 Nov
TI  - Integrated analysis of safety data from 12 clinical interventional studies of 
      plasma- and albumin-free recombinant factor VIII (rAHF-PFM) in haemophilia A.
PG  - 791-8
LID - 10.1111/hae.12724 [doi]
AB  - INTRODUCTION: Antihaemophilic factor (recombinant), plasma/albumin-free method 
      (rAHF-PFM) is a human recombinant full-length factor VIII (FVIII) approved 
      worldwide for the control and prevention of bleeding episodes, routine 
      prophylaxis and perioperative management in adults and children with haemophilia 
      A. AIM: To evaluate rAHF-PFM safety [including adverse events (AEs) and inhibitor 
      incidence] from 12 interventional studies spanning >10 years. METHODS: The study 
      population comprised 418 treated patients (median age = 18.7 years) with FVIII 
      levels </=2% of normal, including 55 previously untreated or minimally treated 
      patients (PUPs/MTPs) from all rAHF-PFM phase I-IV studies, excluding 
      observational safety studies. RESULTS: Most AEs were non-serious; only 93 AEs in 
      45 patients (10.8%) were related to rAHF-PFM. A total of 106 serious AEs (SAEs) 
      occurred in 69 patients (16.5%); the most common were FVIII inhibitors (4.1%), 
      device-related infection (1.0%) and pyrexia (0.7%). The 17 SAEs considered 
      related to treatment consisted of FVIII inhibitors in 1 previously treated 
      patient (PTP) (</=5 Bethesda Units [BU]) and 16 PUPs/MTPs [7/55 high titre (>5 BU), 
      12.7%; 9/55 low titre (</=5 BU), 16.4%]. Overall, the incidence of FVIII inhibitors 
      was 0.36% in PTPs and 29.1% in PUPs/MTPs. No deaths or cases of hypersensitivity 
      related to rAHF-PFM occurred. CONCLUSION: This integrated safety analysis 
      evaluated the safety and tolerability of rAHF-PFM in children and adults with 
      moderately severe or severe haemophilia A in all interventional studies completed 
      to date. It was important to review consolidated evidence as some AEs are rare. 
      There were no new safety signals in a wide variety of clinical settings.
CI  - (c) 2015 John Wiley & Sons Ltd.
FAU - Shapiro, A D
AU  - Shapiro AD
AD  - Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA.
FAU - Schoenig-Diesing, C
AU  - Schoenig-Diesing C
AD  - Global Medical Affairs, Baxter Healthcare, Westlake Village, CA, USA.
FAU - Silvati-Fidell, L
AU  - Silvati-Fidell L
AD  - Biostatistics Department, Baxter Healthcare Corporation, Westlake Village, CA, 
      USA.
FAU - Wong, W Y
AU  - Wong WY
AD  - Research and Development, Baxter Healthcare, Westlake Village, CA, USA.
FAU - Romanov, V
AU  - Romanov V
AD  - Global Medical Affairs, Baxter Healthcare, Westlake Village, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150525
PL  - England
TA  - Haemophilia
JT  - Haemophilia : the official journal of the World Federation of Hemophilia
JID - 9442916
RN  - 0 (Recombinant Proteins)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - *Clinical Trials as Topic
MH  - Factor VIII/adverse effects/antagonists & 
      inhibitors/pharmacokinetics/*therapeutic use
MH  - Hemophilia A/*drug therapy
MH  - Humans
MH  - Infant
MH  - Recombinant Proteins/adverse effects/pharmacokinetics/*therapeutic use
MH  - *Safety
OTO - NOTNLM
OT  - ADVATE
OT  - antihaemophilic factor (recombinant), plasma/albumin-free method
OT  - factor VIII
OT  - haemophilia A
OT  - inhibitors
OT  - integrated safety analysis
EDAT- 2015/05/27 06:00
MHDA- 2016/08/10 06:00
CRDT- 2015/05/27 06:00
PHST- 2015/04/15 00:00 [accepted]
PHST- 2015/05/27 06:00 [entrez]
PHST- 2015/05/27 06:00 [pubmed]
PHST- 2016/08/10 06:00 [medline]
AID - 10.1111/hae.12724 [doi]
PST - ppublish
SO  - Haemophilia. 2015 Nov;21(6):791-8. doi: 10.1111/hae.12724. Epub 2015 May 25.