Inhibitor development against FVIII in previously treated patients with haemophilia A - A retrospective data collection
ABSTRACT In a retrospective study 118 haemophilia A patients from two treatment centres (Berlin and Muenster) were evaluated with respect to safety, i. e. inhibitor development, and efficacy of bleeding control of recombinant FVIII products. During approx. 57 thousand injections with more than 87 million I.U. rFVIII no de novo inhibitor was observed in patients previously treated with pFVIII after switch to a recombinant product. A total of 75 thousand injections with more than 111 million I.U. FVIII had been applied during the investigation period of 14 years. Before as well as after switch of the product type bleeding episodes could be controlled with one to two injections per bleed. Conclusion: According to our results equal safety and efficacy of plasma derived and recombinant FVIII products can be assumed.
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ABSTRACT: The development of neutralizing antibodies to factor VIII (FVIII) is the most serious complication of therapy for haemophilia A. There is now excellent documentation that a large number of both genetic and environmental factors contribute to the risk of FVIII inhibitor incidence. One of the environmental factors that has been proposed as an influence on this complication is the occurrence of FVIII product switching. There are only a small number of clinical studies that have addressed this question, and thus, the amount of objective information available to assess this association is limited. In this review, in addition to summarizing past evidence pertinent to this subject, we present the results of a complementary strategy, a Delphi analysis, to add to the considerations of product switching and FVIII immunogenicity. With the imminent arrival in the clinic of several new FVIII products, the haemophilia community must be prepared to collect prospectively controlled data to better address this important management issue.Haemophilia 03/2014; 20(2):200-6. DOI:10.1111/hae.12283 · 2.47 Impact Factor
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ABSTRACT: Switching between different therapeutic FVIII concentrate types has been postulated as a possible cause of inhibitor development in patient with haemophilia A. In this single-centre, retrospective study, the incidence, titre and duration of inhibitor development in multitransfused patients, defined as patients with more than 150 exposure days (ED), were analysed from January 1970 to December 2007 in relation to ED and the number of switches between different products. Inhibitor titre was assessed by Bethesda assay (before 1998) or Nijmegen assay (after 1998). Medical records of 167 patients were screened, of which 97 patients met the inclusion criteria. Fourteen products of plasmatic origin (different purities) and five recombinant (three generations) were used. Nine patients (9%) developed inhibitors, all transient, low-titre (1.41 ± 0.54 BU) after 323 ± 287 ED in average. Seventeen patients had no product switches of which four patients (23%) developed inhibitors (97 ED in average), whereas 13 patients (77%) did not (ED: 230). Fifty patients switched between plasmatic products only (median: 10 changes) of which five patients (10%) developed inhibitors (ED: 503), whereas 45 patients did not (ED: 932). Five patients switched between recombinant products only (seven changes) of which no patient developed inhibitors (748 ED). Twenty-five patients switched between plasmatic and recombinant products (13 changes) of which no patient developed inhibitors (ED: 1654). No statistically significant differences between patient groups were observed. Neither the number of different FVIII products administered nor the switching of products influenced the incidence of inhibitor in multitransfused patients.Haemophilia 04/2014; 20(5). DOI:10.1111/hae.12439 · 2.47 Impact Factor