title: Safety of Switching Factor VIII Products in the Era of Evolving Concentrates: Myths and Facts.
abstract: Recent advances in the development of factor VIII (FVIII) concentrates offer patients with hemophilia the opportunity to switch to products considered safer or with improved properties. In some cases, product switch occurs due to side effects, convenience issues, or economic reasons affecting clinical choices. Reluctance to change FVIII concentrates is shown by patients and also by their physicians, because of concerns in particular about the risk of inhibitor development. A literature review was performed to retrieve the best evidence regarding safety issues of switching FVIII concentrate in patients with severe hemophilia A. Product switch was not associated with an increased inhibitor risk in four studies in patients during the first 50 to 75 exposure days, or in three studies reporting national switches in Canada and United Kingdom. The latter, the only available study comparing switcher and nonswitcher patients, showed an inhibitor incidence similar to that historically reported in the United Kingdom. In 16 phase III clinical trials and 6 postmarketing studies of FVIII concentrates, few de novo inhibitors were detected in previously treated patients, mostly transient and low-titer, with some additional recurrent inhibitors in patients with previous positive testing. On the whole, although rigorous controlled studies are lacking, literature data do not support increased risk of inhibitor development or other safety issues related to product switch. Therefore, in the presence of clinical needs, the advantages of switching FVIII products should not be missed because of perceived more than evidence-based challenges, in particular in this era of products with improved properties recently introduced or available in few years. Caution, however, is suggested in patients with high inhibitor risk, including in those in concomitance with surgery or intensive treatment. A careful inhibitor testing prior to and after product switch is always needed, to identify real de novo inhibitors and to gather further information in the current evolving scenario, in particular comparing switch and nonswitch patients.
authors.affiliation: Regional Reference Center for Coagulation Disorders, Federico II University Hospital Naples, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Coppola
authors.affiliation: Regional Reference Center for Coagulation Disorders, Federico II University Hospital Naples, Naples, Italy.
authors.forename: Emiliana
authors.initials: E
authors.lastname: Marrone
authors.affiliation: Regional Reference Center for Coagulation Disorders, Federico II University Hospital Naples, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Conca
authors.affiliation: Regional Reference Center for Coagulation Disorders, Federico II University Hospital Naples, Naples, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cimino
authors.affiliation: Regional Reference Center for Coagulation Disorders, Federico II University Hospital Naples, Naples, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Mormile
authors.affiliation: Hematology, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Erminia
authors.initials: E
authors.lastname: Baldacci
authors.affiliation: Hematology, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santoro
mesh_terms: D057915:Drug Substitution; D005169:Factor VIII / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy*; D006801:Humans
chemical_list: C078147:F8 protein, human; D005169:Factor VIII