Inhibitors – What Have We Learned?

A medical session this afternoon chaired by Brigitte Keller-Stanislawski, of the Paul-Ehrlich-Institute and Mike Soucie, of the Centers for Disease Control and Prevention will ask the question, “Inhibitors, what have we learned?”

Inhibitors to FVIII are today the most serious complication of treatment for hemophilia but there is contradictory information about how best to avoid inhibitors, especially in previously untreated patients (PUPs), the most vulnerable group.

Most inhibitors develop within the first 50 exposure days but questions remain about whether the choice of treatment product during that period has an effect on the risk of developing inhibitors. The recently published SIPPET paper suggests that, in PUPs, the risk of developing an inhibitor when using certain recombinant FVIII products is higher than when using plasma-derived FVIII concentrates that contain von Willebrand factor. The study was the first prospective, randomized, multicenter open-label trial in this area. It compared PUPs treated with recombinant factor VIII (rFVIII) to those treated with plasma-derived factor VIII concentrate containing von Willebrand factor (pdFVIII/VWF). The results showed a higher rate of inhibitor (neutralizing antibody) development in the rFVIII-treated subjects compared to pdFVIII/VWF-treated subjects.

However, other datasets do not support the conclusion that the class of recombinant products carries a higher risk. This session will survey these contradictory studies and continue the debate. Dr. Keller-Stanislawski will describe an individual patient meta-analysis of the France coag, UKCHDO and PedNet/ RODIN studies on recombinant products. This analysis involves a very large cohort of PUPS all followed out to 50 exposure days or more. Other speakers will discuss the clinical and laboratory aspects of the immunologic basis of inhibitor development and further data related to the roles of product class and von Willebrand factor. Come to hear the latest thinking on this controversial and important topic.

The “Inhibitors, what have we learned?” session will be held today from 16:30 to 18:00.