"I don't want to bleed anymore, it hurts..."
On 17 April, World Hemophilia Day, Xiaoyou (pseudonym), a child with hemophilia A, bleeds for the third time in April. Because the inhibitors had already appeared, Xiaoyou's bleeding this time was more serious, and the accompanying pain was much more intense.
At night, the child can't sleep in pain, and the parents accompany them all night.
"As a hemophilia patient, I can personally feel that the damage caused to the body by each bleeding is huge, but what is even more helpless is that it is a slow, perennial process." Teacher Guan Tao, chairman of the Rare Disease Care Center of Beijing Blood Friends Home, said.
One patient had multiple poorly controlled bleeding, resulting in joint deformity and disability
Source: Courtesy of Blood Friends House
As an attending physician, I often feel that for patients who have inhibitors, it is really not enough to treat them only after their bleeding...
In addition to on-demand treatment, patients also require preventive therapy
In fact, in every 10 patients with severe hemophilia A, there may be inhibitors in 3 patients. The appearance of inhibitors will not only bring more serious bleeding and a higher risk of disability and death, but also make the originally imported coagulation factor (VIII.) complex completely ineffective, and the patient will return to a state without coagulation factor protection.
Teacher Guan Tao said that for a long time, patients with suppressors were not able to use medicine.
How is this part of the patient treated in the current clinic? In this regard, Lilac Garden contacted Wu Runhui, director of the Hematology and Oncology Center of the National Children's Medical Center and the Beijing Children's Hospital affiliated to Capital Medical University.
Director Wu told Lilac Garden that when exposed to exogenous coagulation factors, some patients will have antibodies (that is, inhibitors) due to the immune response, so the treatment should first remove these inhibitors and pay attention to controlling bleeding, so that coagulation factors can play a normal role. However, the mechanism of the emergence of inhibitors is not fully understood, and how to better remove them is also being explored.
"Inhibitor removal is usually a very slow process, months or even years, and the removal process requires the patient to maintain a good physical condition and try not to bleed. Obviously, on-demand treatment after bleeding is not enough." Director Wu added.
Teacher Guan Tao also said that the patients he was exposed to were drugged after bleeding, and he also faced the problem of recombinant human coagulation VII. The short half-life required repeated multiple infusions, and the use of prothrombin complex in large doses was at risk of thrombosis.
How to achieve no bleeding or even less bleeding during the clearance process of months or even years, reducing the treatment needed after bleeding?
"Preventive treatment." Director Wu said, "The 2018 domestic approved amyclizumab is a bispecific monoclonal antibody that can combine coagulation factor IX. (FIX.a) and coagulation factor X. (FX.) to mimic coagulation factor VIII. (FVIII.), so it will not be affected by the inhibitors of FVIII. and will not induce the production of FVIII. antibodies. It can play a better role in preventing bleeding in patients with hemophilia A and inhibitors."
Rather than the patient's identity, I prefer to see the image of their "bear child"
"The pain after bleeding is worse than death, often 3 or even 7 days of non-stop pain, unable to fall asleep, and not having the energy to do other things." 」 Talking about the pain when bleeding, Teacher Guan Tao said. "One of the children we came into contact with had 45 bleeding episodes in 2021."
Source: Courtesy of Blood Friends House
In contrast, in the cases of children with inhibitors mentioned by Guan Tao, the number of bleeding was significantly reduced, and some even reached an annualized bleeding rate of 0, and the pain caused by bleeding was also reduced.
From the research data of amissizumab, it is indeed possible for patients to achieve less bleeding.
Two randomized, multicenter, open-label clinical Phase III trials, HAVEN 3 (without patients with co-inhibitors) and HAVEN 4 (patients with comorbid inhibitors), showed a 96% to 97% reduction in bleeding events in patients receiving prophylaxis with emelizumab, and 90% of patients with ≤ 3 haemorrhage events per year over one year of follow-up.
The "zero" bleeding brought about by preventive treatment will also make patients with inhibitions less pain after bleeding and have more healing.
"The child is a child with severe hemophilia, and a particularly high inhibitor appears soon after treatment, and bleeds repeatedly. Later, with preventive treatment, there is little bleeding and there is no pain caused by bleeding. I am in good shape now, living and going to school like a normal child. Rather than being a patient, I would rather see the image of a "bear child" that they should have in their age." Director Wu shared a case.
Become a heavy burden behind the "bear child"
In fact, the case shared by Director Wu is only one side of the story, and the other side is that the family needs to do its best to afford the annual treatment costs of more than 100,000 to 200,000 yuan.
According to the survey data of the "White Paper on Chinese Hemophilia Patients", the average annual medical expenditure of children under the age of 12 is about 173,000 yuan, 281,000 yuan for patients aged 12 to 18 years old, and 276,000 yuan for patients over 18 years old. The "2020 China Hemophilia Drug Industry Boutique Report" shows that the cost of hemophilia A combined inhibitors is as much as 10 times higher than that of patients without inhibitors.
Hemophilia is not yet curable, and patients need lifelong medication, so drug affordability is one of the main factors affecting patient treatment.
Currently, coagulation factor VII.a for suppressor patients is included in Medicare. Coagulation factor VII.a is mostly used for on-demand treatment after bleeding, which meets the needs of patients to cope with acute bleeding. However, because these patients still have a high annual bleeding rate, they still face the threat of disability or even death, and the patient's family has added additional costs such as hospitalization, surgery, and rehabilitation.
"With emecilizumab for preventive treatment, a 10-kilogram child costs about 200,000 a year, a 20-kilogram child weighs about 400,000, and so on. There are no drugs available for prophylactic treatment in patients with hemophilia A suppressors within the scope of medical insurance. Many patients may not be able to bear 200,000 and can only abandon this treatment." Director Wu said.
Source: Courtesy of Blood Friends House
In summary, if patients with hemophilia A and suppressors can afford the cost of preventive treatment, and its effect of reducing bleeding or even "zero" bleeding, can it reduce the burden of medical treatment caused by repeated bleeding in these patients? Judging by the data, it is possible.
According to a cost-effect analysis of pharmacoeconomic evaluation reports in patients aged 12 years and older with hemophilia A in the United States who are under 12 years of age and 12 years of age, prophylactic treatment with emelizumab yields the most quality-adjusted life-year QALY and significant savings in treatment costs. For patients older than 12 years, an average of $1.85 million per patient per year can be saved, and for patients younger than 12 years, an average of $720,000 per patient per year.
Teacher Guan Tao told Lilac Garden, "For children with inhibitors, starting to use non-factorial treatment at a young age can prevent bleeding time and joint lesions, reduce the labor loss caused by the patient's illness, and reduce the opportunity cost of the caregiver to take care of the patient."
This means that if the accessibility of preventive therapy in patients with hemophilia A and suppressants increases, the financial burden on patients and the burden of medical care will be reduced.
The blessing of medical insurance policy is one of the keys to promoting the improvement of drug accessibility, and the support of society and enterprises is also very important. Teacher Guan Tao also said that his public welfare organization will raise funds so that patients with financial difficulties can maintain basic treatment.
Source: Station Cool Helo
Director Wu said, "As a hemophilia clinician, the greatest hope is that every child with hemophilia can grow up healthily."
yes. Helps often, heals occasionally. Prophylactic drugs provide more options for clinical treatment and give patients with hemophilia A and inhibitors the opportunity to return to normal life.
Teacher Guan Tao confessed that he had not been able to control it in time and effectively because of multiple bleeding, and finally sat in a wheelchair early. Therefore, he has always hoped that the current little blood friends can live a normal, healthy and unrestrained life free of wheelchairs through effective treatment.
At the same time, Teacher Guan mentioned that to achieve the treatment of a disease, in addition to the availability of drugs, payment protection is also essential. As a group of rare disease patients, it is hoped that the government, especially the medical insurance department, pharmaceutical enterprises, especially rare disease drug research and development enterprises, and social welfare organizations can form a synergy, see the real pain points of each special disease and the classification of patients in a single disease, and jointly explore a path of drug accessibility, affordability guarantee, and sustainable drug research and development. Finally, a virtuous circle of government, medical institutions, enterprise research and development, and patients is formed.
Every small group should not be abandoned, and it is also expected that in the treatment exploration of rare diseases, not only will there be a breakthrough in treatment methods to reduce their disease burden, but also to improve the accessibility of drugs as soon as possible, so that patients can use drugs and reduce their economic burden.
Content Planner: Janz
Legal Review: Wang Jie, Li Anqi
Title image source: DXY design
Illustration Source: Blood Friends Home Courtesy/Station Cool Helo
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