On January 12, Zhu Yuhan, 3 years old and 9 months old, completed the first injection of spinal muscular atrophy (SMA) targeted drug injection in Qingdao, becoming the first patient in Qingdao after the SMA targeted drug was included in medical insurance. On January 1 this year, a 4-year-old boy in Zaozhuang, Shandong Province, received the first injection in the country after the SMA targeted drug was included in medical insurance.
On December 3 last year, the new version of the national medical insurance drug catalogue was announced, and the world's first precision-targeted therapeutic drug for the treatment of rare disease spinal muscular atrophy - Nocinasin sodium injection was listed among them, and since January 1 this year, the price of the drug has dropped from nearly 700,000 yuan / needle to 33,000 yuan / needle.
Difficult diagnosis, high medical expenses, lengthy nursing and rehabilitation... What is the solution to the dilemma of rare disease treatment? The inclusion of therapeutic drugs in Medicare is a big step forward. But this is not the end point, clinicians' awareness of rare diseases, rare disease screening, etc., are issues that need to be promoted for a long time.
When diagnosed, I felt that "the sky has fallen"
"From the beginning of pregnancy, every test of the girl was all the way to the green light, and there were no adverse reactions from the vaccination." Her mother, Zhang Li (not her real name), said she was alarmed when she was eight months old and could not climb. "The old saying goes, 'seven sittings and eight climbing,' let alone climbing, not to mention climbing, lying on your stomach and looking up, and you don't have the strength on both feet."
During the eight-month routine physical examination, the doctors of the local maternal and child health hospital said that they were stunted and needed rehabilitation training. "This child has a problem at first glance, intrauterine hypoxia may hurt the brain nerves, and need to do brain MRI."
These words are like thunderbolts on a sunny day. With the mentality of "big hospitals are more professional", Zhang Li and her husband took you to Jiangxi Children's Hospital for review. Experts suspect that the child has spinal muscular atrophy and ask them to have an electromyography.
Electromyography involves inserting concentric needle electrodes into the muscles. "Such a long needle plunged into the flesh, and it had to be energized, and the girl cried her heart and lungs." There is also blood collection, the child's blood vessels are not obvious, can only collect blood from the top of her head, and the needle is inserted into the top of her head, as if it is inserted into my heart. Zhang Li said.
After examination, in August 2021, the 9-month-old was diagnosed with spinal muscular atrophy type 2.
The rare disease spinal muscular atrophy, known as the number one genetic killer in infants and young children under 2 years of age, is a motor neuron disease that causes muscle weakness and atrophy. It is estimated that there are 1,200 new neonatal SMA patients in mainland China every year, and the stock of patients is about 30,000.
SMA causes damage to the muscles of the patient's whole body, mainly manifested by atrophy and weakness of the muscles throughout the body, the gradual loss of various motor functions of the body, and even breathing and swallowing, and respiratory failure is the most common cause of death. Based on the time of onset and the maximum motor function that can be achieved, patients are divided into four types: 1, 2, 3, and 4.
Among them, type 1 patients generally develop the disease within 6 months, cannot sit alone, have difficulty swallowing and feeding, need to use feeding tubes, and their lungs cannot be fully developed, and many patients need ventilators to help breathe. Patients with type 2 are generally onset at 6 to 18 months and may be able to stand but not walk independently with bracing or external force. Patients with type 3 usually become ill after 18 months and can stand and walk alone, but as the course of the disease progresses, some patients may lose the ability to walk. Type 4 is an adult onset of symptoms that begin after the age of 35, are insidious, progress very slowly, and the muscles used for swallowing and breathing are rarely attacked.
Zhang Li said that she can sit alone, cannot stand, breathing and swallowing are no problem, and others can't see any problems when they are hugged out.
Duoduo's condition is more serious than that of Duoduo. At the beginning of 2020, the 3-month-old Duoduo was diagnosed with spinal muscular atrophy type 1, which is the most serious classification. "It feels like the sky is falling." Duoduo's father, Yu Jianpeng, recalled.
Ventilators, sputum coughers, suction machines... After Duoduo's diagnosis, her home became a small ICU.
"Because the child's breathing and swallowing are very weak, if the lungs are not treated cleanly, it is particularly easy to block the phlegm, and it will suffocate when it is blocked." Yu Jianpeng said that he would do two or three atomization treatments for Duoduo a day, help her suck up phlegm, and pat her on the back. The blossoms need 24 hours a day to take care of them. After the child was diagnosed, Yu Jianpeng and his wife slept no more than 4 hours a day, and the couple took turns to take care of the child.
In addition to daily care, we must also be vigilant against complications, the most serious of which is pneumonia. During May Day last year, Duo Duo was hospitalized for pneumonia and could not swallow, so she could only insert a gastric tube. In September, he was hospitalized with severe pneumonia, and the gastric tube was inserted again, and he did not get better for more than a month. As a last resort, Mr. and Mrs. Yu Jianpeng took their children and a large number of medical equipment from Gansu to Beijing for treatment.
"At present, we have registered more than 2,000 patients from all over the country in real names, the oldest is about 50 years old, and there are very few adult patients, accounting for only 1% to 2%." Mei'er SMA Care Center, a non-profit organization in the SMA field, said that the mortality rate of type 1 children is very high, and type 2 is the largest number of existing patients, and they can survive until about 30 years old without intervention. "In the absence of medicine, care must be done."
Medical equipment on a dobby bed. Courtesy of respondents
Diagnosis is not easy to treat
In October last year, 3-year-old Rui Rui was diagnosed with spinal muscular atrophy type 3, and Rui Rui's mother, Zheng Yan, cried in front of the doctor. When Rui Rui was two years old, Zheng Yan found that the child walked shakily, a bit "inner eight", and needed to slowly get up with his hands after squatting. At the age when other children jumped to kindergarten, Rui Rui could only be held by her grandmother, and often twitched her hands and feet when she slept at night, and her legs were sore and she woke up crying.
Zheng Yan initially found that the child walked abnormally and took the child to the hospital for examination, the doctor could not diagnose the diagnosis for a long time, and it was still the case to change a hospital. It wasn't until last August, when she returned to Wuhan with her child for medical treatment, that she got the answer that broke her heart. Similarly, after the family of Mi Yu was fruitless in the local maternal and child health hospital, she went to Jiangxi Provincial Children's Hospital to find experts for diagnosis and treatment, and finally the diagnosis was confirmed.
Huang Hui, head of clinical genetic counseling at Shenzhen BGI Gene, said that the diagnostic process of SMA is first of all clinical assessment, clinicians according to the medical history of physical diagnosis; followed by clinical testing, including blood muscle enzyme profile, creatine kinase (CK) value, electromyography, etc.; after suspecting that SMA, genetic testing auxiliary diagnosis, genetic testing price is generally 1000 yuan -3000 yuan.
During the clinical evaluation phase, it is important for doctors to understand rare diseases. According to the "2018 China Rare Disease Survey Report", 30% of doctors clearly stated that they did not understand rare diseases.
If the difficulty of diagnosis is the first difficulty on the way for SMA patients to seek medical treatment, then the more difficult is still in the treatment.
Ye Ping, the mother of an SMA child, sent a message to a number of people she knew last December, imploring them to click on a help video posted for her child on a fundraising website. Clicking into her circle of friends is basically all links to fundraising for children.
"There's a lot of pressure on the economy." Yu Jianpeng confessed, "I know that the parents of a child gave up when the child first became ill. When the price of the drug was not reduced, nearly 700,000 yuan a shot, but also had to be beaten all the time, which is a bottomless pit. "In addition to medicines, imported medical equipment such as ventilators and sputum coughers, as well as the cost of entering the ICU, are all economic burdens." In order to take care of the children, Duoduo's mother resigned at home; Zhang Li was also in a long-term leave of absence in order to take her to recover.
Even so, several parents of the children interviewed did not give up. "Even if you sell a house and a car, you have to save your children." Zheng Yan said.
The drug Nocinasin sodium injection for the treatment of SMA was approved for marketing in China in 2019. Clinically, it has been found that it can significantly improve the patient's motor development and reduce the risk of infant death, becoming the first drug in China to treat SMA.
But the drug, also known as a "sky-high life-saving drug," was sold for 699,700 yuan when it was listed, and later dropped to 550,000 yuan. "The child gets 6 injections in the first year, and then 3 injections a year, for life." Mr. Yao said the China Primary Health Care Foundation could subsidize the full dose needed for a year with a single shot of money each year, but they also faced 550,000 yuan a year in drug expenses.
"Rare disease drugs are also known as orphan drugs, because of the difficulty of research and development, small audience, high price, and difficulty in promotion, many pharmaceutical companies are not willing to spend energy on the development of rare disease drugs." Huang Hui said. According to the 2019 China Rare Disease Access Report, there are more than 7,000 known rare diseases worldwide, and less than 10% of diseases have approved treatment drugs or regimens.
The high cost of treatment is followed by routine care and lengthy rehabilitation.
In order to receive better rehabilitation training, Zhang Li took her from Jiangxi to Anhui. She plans to stay in Anhui until the child can walk. "Every day in the hospital rehabilitation class, in layman's terms, is to do exercise. The father of the child is in Jiangxi, about once a month or two. ”
Such rehabilitation training does not have an accurate end time, and it is expected to be 3 years old. "The doctor said that it was no problem for you to walk after the girl, but the way she walked and her posture were not easy to say, so I tried my best to get her closer to the normal child."
When it comes to the future of his children, Yu Jianpeng carries some helplessness: "People say 'raising children and preventing the elderly', this concept I do not have. I just want to take care of her and not make her uncomfortable. Every day when I come home, I can see her smile at me, and I am very satisfied. ”
She was in the hospital for a recovery and stood up with the help of an assistive device. Courtesy of respondents
Try to break the game
In recent years, in order to solve the dilemma of rare disease treatment, all parties are actively working hard.
In 2016, the National Health Commission established an expert committee on rare disease diagnosis, treatment and protection, which made positive contributions to promoting the management of rare diseases in mainland China. In May 2018, the First Catalogue of Rare Diseases was released, including 121 rare diseases, and the diagnosis and treatment guidelines were formulated for all diseases in the catalogue one by one.
In October 2018, more than 50 medical institutions, universities, scientific research institutions and enterprises established the China Rare Disease Alliance, which actively promoted the development of China's rare disease cause.
In February 2019, the Notice on the Establishment of a National Rare Disease Diagnosis and Treatment Collaboration Network was released, establishing a rare disease diagnosis and treatment collaboration network covering 324 hospitals across the country. In addition, China's National Rare Disease Registration System is committed to forming a unified statistical technical specifications and standards for rare disease registration, and uniting the dominant units of national rare disease research to form a collaborative network.
Domestic rare disease drugs are also accelerating their listing.
In 2019, the newly revised Drug Administration Law of the People's Republic of China stipulates that the state encourages research and creation of new drugs, opens green channels for new drugs for rare diseases and children's drugs that are urgently needed clinically, and gives priority to review and approval; for new drugs that treat serious life-threatening diseases and have no effective treatment means, they can be conditionally approved under the condition that clinical trial data show efficacy and can predict clinical value.
The State Food and Drug Administration has established a priority review and approval procedure for rare disease drugs, and established a fast track for rare disease drugs that meet the requirements of clinical needs that have been listed overseas, and completed the approval within 60 days.
Jiangxi's medical insurance policy has given the family a lot of support. "We bought Jiangxi Wei Huibao, and after reimbursement, a needle of more than 100,000 yuan." Zhang Li said that this kind of insurance has an annual premium of 120 yuan per person, and the annual cumulative maximum reimbursement is 2 million yuan.
Such an inclusive supplementary medical insurance is not the first in Jiangxi. Starting from the first half of 2020, various localities have successively launched similar medical insurance for the benefit of the people. At the two sessions of the National People's Congress in 2021, some delegates and members suggested that we focus on new insurance types such as "huimin insurance" and "long-term care insurance", and strive to build a multi-level protection system while jointly building a new pattern of inclusive insurance innovation and sustainable development.
In addition, some social forces are also supporting the families of children with these rare diseases. The Duoduo family received a lot of strange kindness and support, and the foundation helped them release a message for help. In the "Loving Mother Group" of nearly 300 people, mothers from all over the world raised funds for Duoduo, bought daily life and medical supplies for their children, and inquired about Duoduo's condition every day. "Without the help of these people all the way, we would not be able to persist now." Yu Jianpeng said.
In December last year, the National Medical Insurance Bureau released a new version of the national medical insurance drug catalogue, which gave a sigh of relief to the family who were preparing to sell their houses to raise funds. In the video of the drug negotiation scene that attracted the attention of the whole network, after an hour and a half of difficult negotiations, the price of Nocinasin sodium injection dropped from 550,000 yuan to 33,000 yuan, and some of the 33,000 yuan was paid by the medical insurance fund.
"On the day the report came out, everyone in the patient group was particularly excited. I didn't expect to enter medical insurance, and I am particularly grateful for the national policy. Recalling the situation of the day, Yu Jianpeng's voice carried an irrepressible happiness.
It is reported that the medication of rare disease patients has always been the key variety in the process of adjusting the national medical insurance drug list, and since the normalization of the national medical insurance drug list in 2019, there will be rare disease drug varieties entering the medical insurance directory through negotiation every year, and the cumulative number has reached 45. In 2021, a total of 7 rare disease drugs were successfully negotiated, and high-value rare disease drugs appeared in the catalogue for the first time.
Medicare is not the end
"Before we heard that Nosinasin sodium injection entered the preliminary list of the medical insurance directory, it can be negotiated, but for the final 'negotiation', we all feel unlikely, after all, it is too expensive." Zhang Li recalled.
Today, the once "sky-high price life-saving drug" is no longer difficult to reach.
The staff of Mei'er SMA Care Center said that the drug is very useful for patients, especially for young patients, if the child can get the drug treatment earlier, they can prolong life and improve the quality of life. Behind a child is a family, which actually changes many families.
"Rare diseases seem to be a niche thing, but they are not far away from us. For example, in SMA, 50 people have a gene carrier. If both parents are carriers, the child has a 1/4 chance of getting sick. Other diseases have similarities. Said the above-mentioned staff.
Huang Hui believes that the inclusion of rare disease treatment drugs, including SMA treatment drugs, into medical insurance is a win-win measure for patients and enterprises. "It can alleviate the economic pressure on the families of rare disease patients, prolong the life of patients, improve the attention of society to rare disease groups, and is also of great significance for enhancing the willingness of enterprises to develop and accelerating the entry of rare disease drugs into the market."
SMA therapeutics are of great significance to Medicare, but this is not the end point.
Huang Hui introduced that 95% of SMA patients are caused by the homozygous deletion of exon 7 of THE MN1 gene, and genetic testing methods can be used to diagnose SMA patients and screen potential carriers. "The vast majority of rare diseases are genetic diseases, for rare diseases, prevention is greater than treatment, through genetic screening and prenatal diagnosis to avoid the occurrence of diseases as much as possible is to reduce the rate of birth defects, improve the national physical fitness and happiness, reduce the family and social medical burden of effective means."
Beijing News reporter Zhan Shengjie intern Ye Hongmei
Edited by Bai Shuang proofread by Liu Yue