Update #4: MASAC Issues Recommendation on SIPPET

On June 28, 2016, the National Hemophilia Foundation’s Medical and Scientific Advisory Committee (MASAC) issued a recommendation following the published results of the Survey of Inhibitors in Plasma Products Exposed Toddler (SIPPET) The SIPPET study was published in the New England Journal Of Medicine (NEJM) in May 2016. The full text of the SIPPET study is available for a fee to the NEJM.
MASAC’s recommendation consists of five (5) points:

“Based on currently available evidence, MASAC makes the following recommendations:
1. Individuals with greater than 50 exposure days to any recombinant product (i.e. Previously Treated Patients or PTPs) should consider remaining on their current product, since multiple clinical studies have shown that their risk for inhibitor development with any FVIII product is markedly diminished after 50 EDs.
2. Individuals with more than zero and less than 50 exposure days should consider staying on their current recombinant FVIII product, since the differences between SIPPET and numerous other studies may not warrant switching patients who have already initiated a treatment regimen.
3. Newly diagnosed individuals and their caregivers should consider the new data from the SIPPET study in the context of all the accumulated data on inhibitor formation in PUPs and the pathogen safety risk/benefit of the two product classes and consider the following options:
     a. Initiate therapy with a pdFVIII/VWF product in all PUPs.
     b. Initiate therapy with a rFVIII product as previously recommended by MASAC (6).
     c. Initiate therapy with a newer rFVIII product.
4. Regardless of which option is chosen, all PUPs should be enrolled in the ATHN data collection system or a clinical trial to assess outcomes.
5. For all classes of treatment products, the risk for inhibitor formation in PUPs is unacceptably high. All efforts by government, HTCs, patient advocates, and industry should be directed at reducing the risk of inhibitor formation.”

Read the full MASAC recommendation here.
HFA encourages you to have an active role in your own health care and to speak with your doctors regularly on questions of treatment therapy.



  • Inhibitors are antibodies that the immune system develops in response to a clotting factor product used to treat a person with hemophilia.
  • In the SIPPET study, previously-untreated patients (PUPs) were patients under the age of six-years old with severe hemophilia A who had never received factor VIII concentrates before. 250+ PUPs from 14 countries and across five continents were studied.
  • In the SIPPET study, investigators found that in a randomized study, when previously-untreated patients (PUPs) were treated with recombinant factor VIII, there was an 87% higher incidence of inhibitor development than when treated with plasma-derived factor VIII.
  • Donna DiMichele, MD of the National Institutes of Health (NIH) wrote in an editorial in the NEJM entitled Hemophilia Therapy – Navigating Speed Bumps on the Innovation Highway” that this new data must be integrated when making product decisions for children with severe hemophilia A.


Given the importance of this study, and the implications that it could have for PUPs, HFA has taken the following steps:

  1. We are consulting with our Medical Advisory Committee to disseminate available information to our community.
  2. After the release of the abstract in December 2015, we formally reached out to the Medical and Scientific Advisory Council (MASAC) of the National Hemophilia Foundation (NHF) to request that they conduct a full review of this study when it became available.
  3. We requested that MASAC consider the temporary suspension of recommendations (or portions thereof) that state any preference for recombinant factor products until the results of the full SIPPET study could be reviewed.
  4. We have provided three (3) previous updates as information has become available so that patients can discuss their treatment options with their medical provider to make decisions.


While SIPPET focused on previously untreated toddler patients, HFA encourages all patients to maintain an active role in their health care.

  1. Ask Questions: Talk to your doctor about this study, your risk for forming an inhibitor, and about the overall care you receive. Because every patient with hemophilia is at risk of forming an inhibitor, regardless of therapy product, the Centers for Disease Control encourages each patient to be tested annually for one.
  2. Be Involved: Recognize that you play a vital  role in your health care. You have the right to ask questions, make requests, and learn about all your options.
  3. Take Action: Learn more about this study, and share it with your friends and family.

HFA asks every member of the bleeding disorders community to join us as we advocate every day for safe treatments. We will continue to provide updates to the community as we learn more. Together, we are resilient.