Integrated analysis of safety data from 12 clinical interventional studies of plasma‐ and albumin‐free recombinant factor VIII (rAHF‐PFM) in haemophilia A. (25th May 2015)

• Record Type: Journal Article
• Authors: Shapiro, A. D.; Schoenig‐Diesing, C.; Silvati‐Fidell, L.; Wong, W. Y.; Romanov, V.
• Is Part Of: Haemophilia. Volume 21:Number 6(2015:Nov.)
• Page Start: 791
• Page End: 798
• Publication Date: 2015-05-25
• Subjects: Hemophilia -- Periodicals; 616.1572005
• DOI: 10.1111/hae.12724
• Languages: English
• ISSNs: 1351-8216

Abstract

<abstract abstract-type="main" id="hae12724-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hae12724-sec-0001" sec-type="section"> <title>Introduction</title> <p>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.</p> </sec> <sec id="hae12724-sec-0002" sec-type="section"> <title>Aim</title> <p>To evaluate rAHF‐PFM safety [including adverse events (AEs) and inhibitor incidence] from 12 interventional studies spanning >10 years.</p> </sec> <sec id="hae12724-sec-0003" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="hae12724-sec-0004" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="hae12724-sec-0005" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>