Case-Control Pilot Study of the Immune Modulating Effect of FEIBA® on Patients with Haemophilia a and Inhibitors

• Published in: Blood 2015-12, Vol.126 (23), p.4688-4688
• Main Authors: Fernandez Bello, Ihosvany, Álvarez Román, María Teresa, Jiménez Yuste, Victor, Martín Salces, Monica, Iruin, Gemma, Bonanad, Santiago, López Fernández, María Fernanda, Altisent, Carmen, García Candel, Faustino, Rivas Pollmar, María Isabel, Canales, Miguel, Butta, Nora
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V126.23.4688.4688

Background: Immune tolerance therapy (ITT) is the only available therapy for eliminating the inhibitor in patients with haemophilia and high-responding inhibitors. However, it is a very expensive treatment with an efficacy of up to 60%-75%. Factors influencing the outcome of ITT are not completely understood. Some studies have suggested that plasma derived factor VIII (FVIII) concentrates might offer certain advantages in the elimination of the inhibitor when compared with recombinant derivatives. The presence of von Willebrand factor (Auerswald et al,Haematologica 2003;88:EREP05; Kreuz et al,Haematologica 2001;86:16-20) and some molecules with immunomodulatory effect like anti-idiotype antibodies, transforming growth factor-β, HLA type I molecules and soluble FAS ligand in plasma derived concentrates may be involved in such effect (Berntorp et al,Haemophilia 2001;7:109-13; Hodge et al,Br J Haematol 2001;115:376-81; Hodge et al, Haemophilia 2006;12:133-9; Ghio et al, Thromb Haemost 2003;89:365-73). The activated prothrombin complex concentrate (FEIBA®) is a plasma derived product used for bleeding control in patients with haemophilia A and high-responding inhibitors. We hypothesize that FEIBA® may have an immunomodulatory activity due to its plasmatic origin. This effect might be observed in patients with intense treatment with FEIBA® (e.g. prophylaxis treatment) by the reduction in levels of antibodies against FVIII compared with patients on demand treatment with this product. Objective: The aim of this study was to compare levels of inhibitors in patients with severe haemophilia A and inhibitors on demand or under prophylactic treatment with FEIBA®. Methods and results: This was a prospective, observational and multicenter study. A total of 12 adult patients with severe haemophilia A and high-responding inhibitors (6 patients on demand and 6 patients under prophylaxis treatment with FEIBA®) were included. All patients had normal levels of serum creatinine, serum alanine aminotransferase and CD4+ lymphocyte counts at inclusion. Levels of inhibitors were determined by Bethesda assay. Levels of inhibitors in patients on prophylaxis with FEIBA® were lower than those observed in patients on demand treatment but differences were not statistical significant. In most of the patients on prophylaxis, levels of inhibitors went down along the prophylaxis regimen. TableMedical history of patients.Patient NºAgeType of treatmentUsual dose (IU/kg)FrecuencyTiter (BU)Time