The European Haemophilia Consortium (EHC) have organised another one of there excellent Round Table meetings. These events give patient representatives an invaluable chance to hear from some of the leading clinicians on a key issue facing people with bleeding disorders in Europe.
The March 2015 meeting tackled the issue of inhibitors in Haemophilia A. If your immune system responds to a clotting factor product and stops it working it is called an inhibitor. About 30% of people who regularly take clotting factor products will develop an inhibitor.
A lot of the discussion was about whether different types of products or treatment regimes had any impact on the risk of developing an inhibitor – especially when someone hasn’t had treatment before. Previously Untreated Patients are often abbreviated to PUPs in these discussions.
Recombinant or Plasma Derived Products
We heard that the largest retrospective study, the Rodin Cohort Study, does not show a conclusivly whether there is a difference in inhibitor risk between plasma derived or recombinant products.
Therefore, a randomised clinical trial, known as the SIPPET Study, has been started. SIPPET has looked at an effective sample of 270 people with Haemophilia from all over the world. It found a 29% of people developed an inhibitor. It is testing the idea that plasma derived products might be half as likely to cause an inhibitor. However, the study is still ongoing and hasn’t produced an answer yet.
Second or Third Generation Products
The Rodin Study indicated that there might be an increased inhibitor risk from second generation products with a full length molecule. Studies have been conducted in France, the UK, and Canada to try and confirm the finding. The combined studies showed a statistically significant increased risk for previously untreated patients who were on Kogenate. However, this data needs further checking for potential bias so the results are being treated with a lot of caution. Haemophilia Scotland were informed about this issue at the annual meeting with the Scottish Haemophilia Centres and assured that Kogenate is not and will not be used for previously untreated patients in Scotland. At the moment there isn’t a clear explanation for why there might be an increased risk. One of these studies also suggested a risk associated to ReFacto AF but the low numbers of people on the product means that these figures aren’t secure and need further investigation.
The EUHASS project looks at the question of inhibitors a different way. It is a Europe wide adverse events surveillance system. The Centres which talk part regularly report on the number of inhibitors and the number of patients reaching their 50th treatment (as an indication of how many people are at risk of an inhibitor). They found a slightly lower rate of inhibitors at about 26%.
There was a suggestion that it would take a trial which randomly assigned products to previously untreated patients to give stronger results. However, concerns were raised about whether this would be possible while still giving patients fully informed choice.
Patients and Patient Organisations
Thomas Sannie, from the Association Francaise des Hemophilies (AFH) argued that patients are vital to surveillance after market authorisation of any product. This requires engaged and well informed patients who are prepared to make reports. He described the work of the AFH on a project that developed tools to help make reporting adverse events, including inhibitors, part of the culture of the bleeding disorders community in France. This includes a new website which guides patients through the process.
In Scotland the YellowCard Centre Scotland accepts reports of adverse events and side effects from patients and healthcare professionals. However, the system could certainly learn from how the French project has made their equivalent much more user friendly.
You can find out more about this meeting on the EHC website.