Yesterday, the European Haemophilia Consortium (EHC) held its best attended Round Table meeting yet. Almost 80 people came from all over Europe to discuss an important study into inhibitors which is expected to be published very soon. The SIPPET Study is the largest randomized controlled trial every conducted in haemophilia. 216 people with haemophilia have been helping the researchers investigate whether there is a difference in the chances of developing an inhibitor depending on whether someone is being treated with a plasma derived or recombinant clotting factor product.
This issue is so important because inhibitors are the most significant problem with current treatments for haemophilia. They develop when the someones immune system reacts against the clotting factor product they have been treated with. Having an inhibitor means more bleeds, more joint damage, and even a increased risk of death while it persists.
Approximately 30% of people who receive regular treatment for haemophilia will develop an inhibitor. Of these roughly one third will clear it without treatment and two thirds will require treatment. Haemophilia Centres use Immune Tolerance Induction (ITI) to try to tackle inhibitors. This involves giving relatively large amounts of treatment to train the immune system to recognize the product without reacting against it. Even in Europe there are many countries where not everyone who needs ITI can get it. We are fortunate that Scotland is one of the countries with unrestricted access to ITI for those who need it. ITI is successful in 60%-80% of people. That leaves 20%-40% of people who get an inhibitor which can cause long term problems for them.
Although the SIPPET Study data has not been published the initial indications (based on the abstract which has been published) are that it will conclude that there is a higher risk of developing an inhibitor when using a recombinant product when compared with a plasma-derived product, although there is a risk with both classes of treatment. Without the relevant data, clinical organisations and patient groups haven’t yet been able to develop recommendations about how best to respond. However, there was some speculation at the meeting that any advice that was developed might look at using plasma-derived products for people at a higher risk of developing an inhibitor for other reasons (such as genotype, ethnicity, or family history). Most inhibitors develop between the 20th and 30th day that someone takes treatment. Any new approach might be expected to concentrate on that higher risk period. That means that these decisions could have the biggest impact for previously untreated people, like children or babies, and minimally treated people, such a adults with mild haemophilia. However, until the data is available these are just educated guesses.
There are several reasons that it might be unlikely that there will be recommendations to switch, wholesale, from recombinant to plasma-derived products. Not least of there is the concern that plasma-derived products are inherently more vulnerable to new blood borne pathogens such as viruses or prions. This consideration is particularly acute in Scotland, and the rest of the UK, because of concerns about vCJD. Although there are no cases of infections with a blood borne virus or vCJD from the products currently available in Scotland, nobody wants to be complacent. It is also worth remembering that the volumes involved in recombinant treatment are lower which has advantages when treating children.
What was very encouraging was that clinician after clinician at the meeting stressed the importance of giving patients and parents the information they need to understand their choices. There was also a strong commitment to developing any guidance or recommendations in partnership between clinicians and patients. In the UK, the United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO) Inhibitors Working Party will play a leading role. Here in Scotland, we will work through the new Scottish Inherited Bleeding Disorders Network to respond to changing knowledge about inhibitors and adapt any recommendations from UKHCDO, the EHC, or the World Federation of Hemophilia (WFH) for use in Scotland. There is currently no date for the publication of the SIPPET study but we will keep you informed as soon we know more.
CEO, Haemophilia Scotland