The SIPPET Study

SIPPET Study Shows Potential Difference in Inhibitor Rates

ASH 2015 (Orlando, December 5-8) The SIPPET (Survey of Inhibitors in Plasma-Product Exposed Toddlers) study was conducted to compare the occurrence of factor VIII (FVIII) inhibitors in minimally treated and previously untreated patients (PUPs) treated for 50 exposure days (EDs) with locally-available VonWillebrand-containing plasma-derived FVIII (pdFVIII-VWF) concentrates versus those treated with recombinant FVIII (rFVIII) concentrates in each country.  It took place between January 2010 and December 2014 with information collected on 251 children less than 6 years of age with severe hemophilia A, from 14 countries in Africa, North and South America, Asia, and Europe. According to data presented in an oral abstract session at the American Society of Hematology (ASH) 2015 Annual Meeting, the study screened 303 patients and only 251 patients met the study criteria. They randomly assigned 125 to pdFVIII-VWF and 126 to rFVIII; patients received treatment between 1 and 50 exposure days, with half having only 1-22 exposure days of the planned 50. There were 76 patients who developed inhibitors (35%); the risk of developing an inhibitor was 1.87 fold higher using locally-available rFVIII than compared to those using pdFVIII-VWF. The study results are limited in that it only compared classes of factor products (all rFVIII versus all pdFVIII), not specific treatment products, it did not include the same products in all countries even within these classes, and it did not include the many newer standard or extended half-life rFVIII products that have been brought to the market since the study began in 2010. Also, the study only looked at the period of up to the first 50 exposure days to which patients were exposed and did not address the issue of changing factor products after 50 exposure days. It is also important to remember that there may be other factors such as family history of inhibitors, genotypes associated with higher risk of inhibitor development which may influence the individual’s inhibitor risk in addition to the product type which have not been reported yet in the communication of results at the ASH meeting. National Hemophilia Foundation’s Medical and Scientific Advisory Committee (NHF-MASAC) has stated that the data presented is incomplete and should be reviewed fully once it is published.