The results of the SIPPET (Survey of Inhibitors in Plasma-Products Exposed Toddlers)
study were presented at a plenary session of the recent American Society of Hematology (ASH) conference. SIPPET was a randomized study which took place between January 2010 and December 2014 that collected data on 251 children <6 years of age with severe hemophilia A from 14 countries in Africa, North and South America, Asia and Europe. The purpose of the study was to compare the incidence of factor VIII (FVIII) inhibitors in minimally treated and previously untreated patients (PUPs) treated with von Willebrand (VWF)-containing plasma-derived (pd) FVIII concentrates versus those treated with recombinant FVIII concentrates.
Following are a few important features of the study:
- The ASH presentation suggested that in PUPs, the combined risk of developing a high or low titer inhibitor within the first 50 exposure days (EDs) when using recombinant factors was 1.87-fold higher than when using VWF-containing plasma-derived factor concentrates. For high-titer inhibitors only, the risk was 1.7 fold higher for those using the recombinant class of products, but this difference did not reach statistical significance.
- SIPPET compared classes of products, not specific treatment products within or between classes. The comparison was between intermediate-purity pdFVIII products that contain VWF, not all pdFVIII products, vs. first through third generation recombinant products only. Newer products that have been brought to the market since the study began in 2010 were not included within SIPPET.
- The study only looked at the first 50 EDs and did not address the issue of product switching after 50 EDs.
While this is potentially an important study, the data are incomplete at this time, and it will be critical to review the full study report when it is published. We do not yet know when or where the study will be published.
There are numerous other studies that have been published or are ongoing that address the issue of inhibitor development in PUPS. The field is constantly evolving as is the availability of new treatment products that were not part of this study.
Other on-going studies may prove to have additional relevance in determining which product to begin treatment with for PUPS. In addition to product type, other factors of importance in determining inhibitor risk include whether there is a family history of inhibitors and whether the patient’s genotype is one that is associated with a higher risk of inhibitor development. All of these factors need to be taken into account when choosing a product for initiation of factor replacement in PUPS.
At this time, MASAC is recommending that families of minimally treated or previously untreated patients discuss the issues surrounding product selection with their hemophilia treater.
At its upcoming meeting in February, MASAC will carefully review the full study report, if published, as well as reports from other studies that have been published, before deciding whether to issue a revised recommendation on the use of recombinant products in PUPS.