This page contains a Flash digital edition of a book.
Factor VIII products


Recombinant versus plasma products


This article summarises the debate on whether recombinant products are more immunogenic than plasma products


H Marijke van den Berg Associate Professor, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, The Netherlands


Between 20 and 30 percent of patients with severe haemophilia A develop inhibitory antibodies against infused FVIII products. This makes usual treatment with FVIII and prophylaxis impossible, impairs the patient’s life expectancy and increases the burden of the disease.1


The risk that a patient will


develop an inhibitor depends on a variety of genetic and non-genetic risk factors.2–4 From the discovery of cryoprecipitate in the 1960s to the new generation of factor VIII and IX products with an extended half-life, much has been achieved.5


The human immune deficiency virus (HIV) tragedy in the 1980s has been a driving force in the introduction of new methods for viral inactivation. It has stimulated the rapid development of future generations of safe plasma products first for HIV and later also for hepatitis C.6,7


VIII and IX genes and the subsequent development of products of recombinant technology not only led to a future with safe products but also was a promise for sufficient supply.8


Systematic review of comparisons The focus of patients and physicians in


The elucidation of the factor


the 1980s and 1990s was towards safe products, and the prevention of transmittable pathogens had the highest priority. Before that time, plasma products were often produced locally and the authorisation was governed by local regulations, often with only small pre-licensing studies on


pharmacokinetics. In the early 1990s, the correlation between two particular plasma products and the development of inhibitors were recognised.9


This fuelled


interest in the importance of the occurrence of allo-inhibitory antibodies. With the introduction of recombinant products, regulators enforced stricter guidelines that necessitated larger studies before market authorisation could be conducted. Formal studies on previously undisposed patients (PUPs) were introduced and patients were tested at least every three months within the first 50 exposure days of factor VIII. This led to a clear increase in inhibitors


www.hospitalpharmacyeurope.com


3


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36