Rare but not invisible. Challenges for the system

Rare and ultra-rare diseases are, as Deputy Health Minister Ursula Demkow stressed, a special area of European cooperation - only through the exchange of experience and information is it possible to maintain therapeutic standards for groups of patients, which sometimes number several or a dozen people nationwide. A special dimension of this cooperation is the network of expert centers dedicated to rare diseases. We have 44 of these in Poland, and the deputy head of the health ministry responsible for the area of rare diseases estimated that this is far too few, given that there are more than 2 million people with rare diseases. Even if there are therapeutic options for only a small fraction, the number of patients who seek or expect help exceeds the capacity of these centers. Ursula Demkow announced the establishment of more, which will not have to meet such stringent criteria as the centers in the European network (although they may evolve in that direction over time).

Developing centers for adult patients with rare diseases and transitional, twin centers where pediatric patients could be safely moved into the adult care system is also a challenge, she stressed. Advances in rare disease treatments that radically extend life in many disease entities also generate logistical challenges, and patients may even feel abandoned by doctors who have cared for them often as if they were their own children. - What we need is a transition model that would begin at age 16, for example. For two or three years, doctors would take care of patients together," explained Prof. Demkow.

An important system declaration that was made during the panel concerns the changes in AOS implemented by the National Health Service. - I am working to ensure that degression does not apply to patients with rare diseases, which specialist clinics cannot and should not transfer for treatment in AOS under pain of financial penalties, the deputy minister said. Good news both for patients and providers (hospitals) is the finalized work on a basket of diagnostic tests, which will be possible to bill together with hospitalization. It's a change that will allow hospitals to breathe financially, as they won't be charged for tests, and for patients it will mean accelerated diagnostics.

There is no doubt that financial issues affect (although they shouldn't) the accessibility of patients with rare diseases not only to diagnosis, but also to treatment. Pawel Voytovich, president of the Matio Foundation - Foundation for Helping Families and Patients with Cystic Fibrosis, stressed that a model of patient care has already been developed, based on small centers located outside of centers dedicated to rare diseases. The issue is, first and foremost, the safety of the patients themselves, who should not move around large hospitals where the risk of infections increases. The drug program is being implemented in these centers. - We are thankful for the inclusion of patients aged 2-12," he said, adding that in theory there should be no inequality, no barriers, in access to treatment at this time. However, this, he admitted, is not the case. Some directors are concerned about the financial risks associated with the drug program, with no assurance that the payer will pay the entire liability. - The idea is that patients should not have to look for hospitals that are in good or better financial shape, he said.

Hemophilia, like cystic fibrosis, is a long-recognized, genetically determined rare disease, the symptom of which is recurrent bleeding, both externally and into body cavities, joints, muscles which leads to disability. It is also a disease, in the public mind, that is well taken care of, as a health program has been in place since 2008, and thanks to this, patients have access to clotting factors. However, this does not mean that there are no unmet health needs. Ewelina Matuszak, president of the Sanguis Foundation - Hemophilia and Related Hemorrhagic Diathesis reminded what it means - from the point of view of the family, the parent, the child - to have to administer clotting factors intravenously every other day. - Each time, parents perform medical procedures on their children at home, she pointed out, reminding that such a number of insertions must lead to destruction of veins. Parents must regularly perform subsequent administrations, including when children ask and negotiate: - Not today!

And while the widespread availability of clotting factors has already protected an entire generation of hemophilia patients from disability, there are now new options available to patients in other European countries, while in Poland they are available to a small group of patients. The drug in question is subcutaneously administered emicizumab. t- The form of administration matters," Ewelina Matuszak stressed, pointing out the enormous psychological burden of turning one's home into a treatment room and involving family members in difficult (realistically difficult when there are problems with insertion, whether in children or, for example, adult patients, but even if they have mental disorders or intellectual disabilities) medical procedures. Matuszak also spoke of an intermediate way out, i.e., access to prolonged clotting factors, which would make it possible to dispense with, for example, one administration per week. This, too, is only a postulate for now. Admittedly, on July 1, 2024, the health ministry decided to reimburse emicizumab therapy for a selected group of children while three months later this group was slightly expanded. Subcutaneous treatment applied once every two or four weeks was given to the sickest young patients with severe hemophilia A. This, however, does not exhaust the problem. As recently as last fall, the Sanguis Hemophilia and Related Hemorrhagic Diathesis Foundation launched a petition by parents, relatives and friends of children with hemophilia to make emicizumab bleeding prophylaxis available to all children with severe hemophilia A from birth to age 18 without meeting additional criteria. - The petition has been signed by more than 100,000 people, she stressed.

Deputy Minister Ursula Demkow assured that the Health Ministry intends to move in the direction of expanding reimbursement, including to adult patients. She recalled that at the moment patients with hemophilia can benefit from short- or long-acting clotting factors, a subcutaneous drug, which, however, does not give equally good results in everyone, but soon there will probably be a gene therapy that will simply cure children. - Gene therapy is a matter of the future. Subcutaneous drugs in the here and now make a difference in the lives of both patients and their families," retorted Elzbieta Matuszak.

- The temperature of the discussion proves the importance of timing the implementation of solutions that are in line with current medical knowledge, i.e. with the diagnostic and therapeutic standards in force in Europe," assessed Dr. n. ekon. Malgorzata Galazka-Sobotka, director of the Institute of Healthcare Management at Lazarski University in Warsaw, stressing that as a system we should aim for the highest efficiency measured by treatment results, quality of life, but also costs. - We should aim to implement care regimens in line with the latest medical knowledge as soon as possible, she left no doubt. In her view, as the EU's sixth economy, a country that has achieved considerable success in many areas, it is simply inappropriate to stand apart in the area of health care. This is also evident in the area of rare diseases. - For decades, these patients remained on the margins. Today we have technologies, and there are advances in the organization of care," the expert admitted.

Dr. Galazka-Sobotka pointed out that in the treatment of hemophilia, a drug program and a health program coexist side by side. They differ organizationally, each of these solutions, she explained, has advantages and disadvantages. She pointed out that the advantage of the drug program is that it provides patients with coordinated and comprehensive care. - For the patient, the pathway does not matter much. What matters is if and when he will have access to what is already standard in other countries," she stressed, pointing out that the effectiveness of prevention includes not only the health problem itself, but also quality of life or reducing the impact of the disease on the ability to pursue social, family and professional goals. - This is an investment with a guaranteed rate of return, because with the use of such therapies it always turns out in the end that the payer's expenses for patient care decrease, she pointed out.

Among the thousands of rare diseases, there are those such as hemophilia or cystic fibrosis - high-profile and socially recognized, but there are others that only specialists, the patients themselves and their families know about. This group includes Alagille syndrome, a rare genetic disease. People struggling with Alagille syndrome suffer from, among other things, chronic cholestasis, which manifests itself in persistent itchy skin and jaundice, or papular skin lesions, caused by the deposition of cholesterol. Persistent cholestasis can develop into progressive liver fibrosis and lead to cirrhosis and complete failure of the organ. Up to one-third of patients may require liver transplantation while still in childhood, and eventually transplantation proves necessary in more than half of Alagille syndrome patients. The only "upside," explained Prof. Anna Liberek, MD, head of the Pediatric Department, COPERNICUS, St. Adalbert's Hospital in Gdansk, is the uncomplicated diagnosis. - These patients do not go through a diagnostic odyssey that lasts many months or years, she said. The development of molecular biology makes it possible to determine the causes of jaundice appearing in a child, and a set of clinical features - including characteristic facial features (widely spaced eyeballs, pointed chin, prominent forehead) , certain defects of the heart, vision and skeletal abnormalities make it possible to make a diagnosis of Alagille syndrome.

The high concentration of bile acids in the blood, caused by cholestasis, leads to liver damage, but a huge problem is also the persistent itching of the skin all over the body. - It's a real torture," the expert said. Lack of sleep at night, depression, suicidal thoughts and attempts - this is the reality of patients for whom, until now, only conservative treatment, administered outside of registration indications, has been possible. . - Rysio would wake up several or more times during the night, scratching himself until he bled. Initially, the medications administered did not bring any relief, nor did the cooling pajamas with hand pads we found on the Internet to reduce scratching and the formation of further wounds on the skin," said Magdalena Monastyrska-Kryczmanik of the Liver Association for Sick Children, mother of the little patient. The now six-year-old boy did not go to kindergarten, his mother had to give up her job. The situation was changed when the boy became eligible for a clinical trial of a European-registered drug in the ileal bile acid transporter (IBAT) inhibitor group. The improvement was rapid, within a few months the pruritus had completely disappeared , the boy went to kindergarten and his mother was able to return to work. IBAT inhibitors, Prof. Liberek said, effectively reduce the absorption of bile acids responsible for the occurrence of pruritus. - This is simply unbelievable - within weeks the concentration of bile acids decreases, the itching of the skin subsides, and we hope that in the long run patients will not require liver transplantation, the expert stressed. Drugs in this group are currently available in Poland for narrow groups of patients under the Rescue Access to Drug Technologies ( RDTL). - We are fighting to include patients with Alagille syndrome in the drug program, which will provide coordinated care and allow patients to qualify for treatment based on clear criteria, Prof. Liberek stressed. - What I would like for all children with Alagille syndrome is for them to have access to modern therapies, because they produce results. The family can function fairly normally, it really changes a lot," added little Lynx's mother.

Persistent itching of the skin, combined with chronic fatigue, is also one of the problems of adult patients, especially female patients (90%), suffering from Primary Biliary Cholangitis (PBC). The disease affects people over the age of 40In this group, said Maciej Janik, MD, from the Department of Hepatology and Internal Medicine at WUM, early diagnosis would be of great importance. It is not complicated - it consists in performing the so-called liver panel, which should include, among other things, determination of alkaline phosphatase (ALP) concentration in the bloodThe expert stressed that primary care physicians can issue a referral for ALP testing, but in practice it is ordered very rarely. As a result, patients wait several months or even several years for a diagnosis. - We have advocated that the determination of the liver marker ALP be included in the "My Health - Adult Health Balance" program in the group of people over 40. This is not an expensive test, and its use would be helpful in catching liver diseases that, if untreated, cause complications including cirrhosis, leading to the need for organ transplantation, Dr. Janik said. The Health Ministry has not decided to take this step. However, the hepatology community is hoping for further dialogue on the issue, stressing that attaching ALP testing to the prevention program would be crucial in terms of effective diagnosis of various liver diseases, including primary cholangitis.

As Dr. Janik stressed, the situation of patients with primary cholangitis in terms of quality of life associated with persistent itching of the skin and chronic fatigue is extremely difficult. Adapting to the disease, the symptoms of which force a reduction in social and professional activity, if only because constant scratching is associated with a lack of hygiene, and fatigue takes away the strength to function on a daily basis, is a major challenge. - The disease stigmatizes and suicide attempts also occur in this group, the expert said. Although a lot of good things have happened in the field of rare diseases in recent years, as experts stressed during the discussion, the expectations and needs of patients are even greater. That's why, as Stanislaw Maćkowiak, president of the Federation of Polish Patients and the National Forum for Rare Disease Therapy ORPHAN, said, work is currently underway on a law on rare diseases, which will outline the framework for institutions responsible for health policy and, above all - strengthen the position of patients. The team, chaired by Stanislaw Maćkowiak, has taken as a reference point Italy, which in many respects (for example, in the area of screening) is regarded as a model country for dealing with challenges in the area of rare diseases. - We have to do it," stressed Stanislaw Maćkowiak.