Working together against rare diseases

Patients with a rare disease are often not easy to recognise on the basis of symptoms, precisely because they are so rare. "That's why it usually takes a long time for these patients to get the right diagnosis," says Alberto Pereira Arias, professor of Internal Medicine, in particular Endocrinology, at Amsterdam UMC. "After that, it is a matter of looking for the right treatment, because it often involves complex syndromes involving multiple specialisms. That makes patients with a rare disorder extra vulnerable." 

Nevertheless, patients with a rare disease are certainly not rare. With more than 6,000 different rare diseases, there are easily about 36 million people in Europe, twice the entire Dutch population that have a rare disease. Partly due to an active lobby of patient associations, the European Commission stated in 2011 that 'every patient with a rare disease has the right to choose care within the EU countries and to be reimbursed by public or private healthcare providers'. In other words, every patient in the EU, regardless of their place of residence, is entitled to the same treatment. 

Together with patients 

"That was the impetus for the establishment in 2017 of 24 European Reference Networks, or ERNs for short," says Arthur Wilde, emeritus professor of Cardiology. From that moment on, every rare disease fell under one of those 24 ERNs. Wilde became coordinator of the Reference Network for Rare Heart Diseases (GUARD-Heart), Pereira of the Endo-ERN, which includes rare hormone and metabolic diseases. The EU funds the organisation of the networks, in which only centres of excellence in the member countries can participate. 

Wilde sees the high level of involvement of patient organisations as a direct result of the ERNs. "Leaflets were made in layman's terms for every rare heart disease. Websites in everyone's language were launched with up-to-date and reliable information. Patients participated in meetings and the development of guidelines. I see that great involvement as a great result." 

Immediately afterwards, he mentions the design of the Clinical Patient Management System (CPMS). Whereas in the past there were sometimes peer consultations by e-mail, now difficult problems of patients are discussed together by international experts on a protected platform in a privacy-proof way. To finalise a diagnosis, to determine a treatment, or to determine what alternative options are if a treatment does not work well. "Without the ERNs, such a CPMS probably would not have come about," says Wilde. 

Better care 

The fact that every patient has the right to the same optimal treatment does not mean that health care in every country must be brought to the same level. Rather, it is the case that the available expertise is made accessible to everyone. The CPMS makes a strong contribution to this. Pereira cites as an example a Greek boy with Cushing's syndrome in whom the tumor could not be found. He was taken to the Netherlands, operated on here and then further cared for in Greece. Another CPMS example, the operation of a Bulgarian girl with Turner syndrome in another country, did lead to consequences for healthcare in Bulgaria itself. "The team that brought the girl in for consultation has since grown into Bulgaria's center of expertise that other domestic centers now refer to. In this case, we did see an improvement in care in the country itself," says Pereira. 

Knowledge building 

An important consequence of the ERNs is also the introduction of patient registrations, the databases in which the data of patients with rare diseases are stored. "This way you get much more data about these diseases than if each country did it individually," says Pereira. These growing registrations are valuable for better diagnoses, more insight into both the natural course and treatment of the diseases, the development of treatment guidelines, and not to forget the increasing opportunities for research into all those rare diseases. "This makes the position of the ERNs increasingly important," says Wilde. "By now, every healthcare institution knows which national centers of expertise to turn to for patients with a certain rare disease. 

These centres also provide access to the ERNs. In any case, rare diseases are becoming increasingly important for academic hospitals such as Amsterdam UMC. A few years ago, about 30 percent of our hospital activities were already focused on this. That will only increase. So the ERNs are also gaining more and more weight in economic terms." 

This can also be seen in the research, because scientific research is increasingly being published on the basis of patient registries. Pereira: "Simply because that's where an important part of the knowledge building takes place. If you want to do research into rare diseases, you can no longer ignore the ERNs. Not a member? Then it will soon be difficult to obtain European subsidies for research into rare diseases." Wilde sees something similar happening in healthcare: "All kinds of new treatments are appearing for rare diseases, such as mRNA therapy, CRISPR-Cas, CAR T-cell therapy. Chances are that you can only start using such therapies if you are an ERN-member. Training and knowledge transfer? Within the ERN."