Pasca Samantha, MD, MSc1, Zanon Ezio, MD1, Pollio Berardino, MD 2, Ricca Irene, MD2, Marino Renato, MD3, Paolo Simioni, MD1
1Hemophilia Center, University Hospital of Padua; 2Regina Margherita Children Hospital of Turin; 3Haemophilia and Thrombosis Center, Giovanni XXIII Hospital of Bari
Backgroud
The appearance of inhibitors is the most serious complication in hemophilia A. The primary objective is their eradication. When the primary ITI fails, another ITI-R is often started. We report three cases of ITI-R with the human cell line-derived recombinant FVIII (human-cl rhFVIII), simoctocog-alfa.
Methods
Three previous treated patients with severe haemophilia A who developed high-titre inhibitors to different FVIII concentrates were treated with simoctocog-alfa for ITI-R. Complete success of ITI-R was assessed based on achievement of an undetectable inhibitor titre (<0.6 BU/mL), FVIII in vivo recovery (IVR) ≥66% and half-life ≥6 hours
Results
At the onset of ITI-R with human-cl rhFVIII two patients were children and one was a 48-year-old adult. The children had failed a previous ITI with the same FVIII concentrate that caused the inhibitor development, while the adult patient had failed two consecutive ITI performed with plasmaderived FVIII enriched by von Willebrand factor (pdFVIII/vWF), and with moroctocog-alfa, respectively. All patients presented at least three risk factors for a poor-prognosis ITI-R: previous ITI failed, age >7 years, more than 2 years since inhibitor diagnosis and ITI start. In all cases the peak historical inhibitor titre was ≥10 BU/mL, ITI-R treatment consisted of 200 IU/kg simoctocog-alfa daily for all three patients. One child has achieved complete tolerization, with an undetectable inhibitor titre, an IVR≥66% and a half-life ≥6 hours after 6 months. The remaining two patients presented an initial disappearance of inhibitors after 7 and 22 months, respectively, without IVR and half-life normalisation. The inhibitor titre subsequently increased, reaching 1.9 BU/ml and 1.0 BU/ml, respectively. In these two cases the ITI-R were then considered as a partial response to treatment.
Conclusions
A treatment with human-cl rhFVIII could be an important option in achieving a complete or a partial immune tolerance also in a population of patients with high-titre inhibitors, and presenting some risk factors for poor ITI.
References
1) Immune tolerance induction(ITI) in haemophilia A – patients with inhibitors – the choice of concentrate affecting success. Kreuz W et al. Haematologica 2001;
2) Immune tolerance induction in haemophilia A patients with inhibitors by treatment with recombinant factor VIII: a retrospective non-interventional study. Rivard GE et al. Haemophilia 2013;
3) The principal results of the International Immune Tolerance Study: a randomized dose comparison. Hay CR et al. Blood 2012;
4) Induction of immune tolerance inhaemophilia A inhibitor patients by the ’Bonn Protocol’: predictive parameter for therapy duration and outcome. Oldenburg J et al. Vox sanguinis 1999;
5) Immune tolerance induction in patients with severe hemophilia A with inhibitors. Ryu JE et al. Blood Res 2015.