Our study is the first to use CHIRA database to study the use of prophylactic treatment in PWH in China and its relationship with treatment costs. We found that the proportion of hemophilia A patients and hemophilia B patients using prophylactic treatment in urban China was 3.2% and 3.4%, respectively. In addition, PWH in urban China have a heavy financial burden. The total annual per capita medical expenses for hemophilia A patients were ¥31022, of which 69.0% (¥21400) was caused by hemophilia. And the total annual per capita medical expenses for hemophilia B patients were ¥46084, of which 91.5% (¥42055) was caused by hemophilia. OOP costs from hemophilia account for more than 30% of per capita disposable income. Meanwhile, we found that there was a statistically significant difference in total annual costs between patients with and without prophylactic treatment. The cost of medical care for PWH who used prophylactic treatment is 16 times that of those who did not use it.
We found that the rate of prophylactic treatment in hemophilia was as low as less than 4%, which is close to the figure (3.6%) in a previous study in Shanxi province, China. Between 1999 and 2010, prophylaxis use in the US increased from 31% to 59%, and 75% of children and youths (<20 years) received prophylaxis treatment in 2010. Besides, a study in the Netherlands showed that 29% of Dutch PWH received prophylactic treatment in 2001.9 Thus, the proportion of hemophilia patients receiving prophylactic treatment in China is far lower than that in some developed countries. The reasons for the low proportion of prophylactic treatment maybe as follows. Firstly, at present China's domestic production of clotting factor Ⅷ products far cannot satisfy the needs of patients. In addition, because of the high drug storage requirements, most blood products and injectable drugs are only available in the tertiary hospitals. This may result in high indirect costs, including the time spent waiting in the hospital, the costs of travelling to and from the hospital, etc. Furthermore, according to the current regulations of medical insurance, injections are not allowed to be discharged with drugs, and the requirements for blood products are more stringent. So if a patient needs prophylactic treatment they should go to the hospital every time.
The total annual per capita medical expenses for hemophilia A patients and hemophilia B patients were ¥31022 and ¥46084, of which 69.0% and 91.5% was caused by hemophilia, respectively. A European study estimated the mean per-patient annual direct cost of severe hemophilia ranges from EUR 116963 to EUR 313068, approximately 34 to 87 times higher than the mean per-capita health expenditure. And the clotting factor replacement therapy accounted for 99% of the total costs. WHO reported that the average annual cost of prophylaxis for PWH is USD100000 per individual, with prophylactic consumption of pdFVIII being 1900-8200 IU/kg/year in developed countries., While according to a report by the WHF, the annual per capita consumption of coagulation factors by PWH in China is more than six-times lower than that of the minimum adequate treatment levels as established by the WFH. The medical costs and the proportion of clotting factor usage of hemophilia patients in China are lower than those in developed countries, which may indicate that most hemophilia patients in China have not been adequately treated.
The general superiority of prophylactic treatment over on-demand treatment has been demonstrated that prophylactic treatment can greatly improve the average life expectancy and quality of life of hemophilia patients.  But due to the high cost, most PWH in China cannot afford the prophylactic treatment, resulting in their poor quality of life. Although hemophilia treatments are covered by China's medical insurance coverage, under the pressure of the control assessment of drug proportion and total medical insurance amount, doctors' prescription of drugs is constrained, and the reimbursement policy of drugs is almost useless. However, on January 30, 2019, China abolished the single drug proportion assessment. With the elimination of the assessment of drug proportion, the pressure on hospital procurement and physician prescription of hemophilia drugs will be further alleviated.
In fact, hemophilia is a rare disease with a clearly effective treatment. And once hemophilia patients get effective prevention and treatment, their life expectancy and quality of life will be greatly improved. Therefore, we hope that Chinese pharmaceutical companies can accelerate the development of domestic hemophilia drugs, and medical institutions can increase the reserves of hemophilia drugs to ensure that hemophilia patients can have drugs available. In addition, we call on the Chinese government to further increase the reimbursement level for hemophilia, so that hemophilia patients can afford routine treatment for hemophilia. With the socio-economic development of China, we also believe that through the joint efforts of all parties, more and more PWH can gradually understand the benefits of prophylactic treatment and use prophylactic treatment.
Limitation of this study
Due to our small sample size, the extension of the study to PWH nationwide may be limited. The CHIRA only included patients with URBMI and UEBMI, while PWH covered by the NRCMS were excluded because our data did not provide relevant information. Because hemophilia is a rare disease with small number of patients, it is difficult to obtain sufficient sample size data. And the definition of prophylactic treatment may introduce some bias. We determined whether PWH used prophylaxis by observing their medication behavior and the dose of coagulation factors. The results obtained by this method may not be accurate.