Prophylaxis versus on-demand regimens to prevent arthropathy in real-life patients with hemophilia A

• Main Authors: Shi-JieLai, 賴仕杰
• Other Authors: Edward Chia-Cheng Lai
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/sc5ku5

碩士 === 國立成功大學 === 臨床藥學與藥物科技研究所 === 106 === Introduction Hemophilia is an inherited bleeding disorder resulting from the absence or deficiency of coagulation factors. There are two major types of hemophilia, hemophilia A and hemophilia B. Since the introduction of clotting factor concentrates, regular prophylaxis and more comprehensive care have led to an increased life expectancy of persons with hemophilia (PWH). The National Health Insurance Program has updated the reimbursement guideline for the use of prophylaxis therapy inpatient with hemophilia in 2014. However, there is no sufficient evidence to support what the implement status nowadays and how treatment behavior changed after new national guideline being introduced. Nonetheless, the effectiveness of prophylaxis regimen of hemophilic arthropathy in Taiwan remains unknown. Objective The objectives of the study are as the following: (1) To investigate population-based epidemiologic data of hemophilia in Taiwan, including prevalence, age distribution, incidence rate and mortality rate of hemophilia patients in Taiwan. (2) To analyze utilization patterns of coagulation factor for hemophilia patients including the dosage, cost, and utilization of healthcare resource, including the number of visits, and related medical costs. (3) To study health outcomes of patients with hemophilia including the annual bleeding rate of patients with hemophilia and the time of joint outcomes (e.g., arthropathy and joint replacement) for hemophilia patients from their birth date. (4) To explore the comparative risk of arthropathy between prophylaxis vs on-demand regimens. Materials and methods We used the Taiwan National health Insurance Research databases for the following studies. Firstly, we constructed cohorts from 2003 to 2015 of diagnosed hemophilia patients to explore the epidemiologic data. Secondly, we used data of male patients with hemophilia to conduct the research of utilization pattern of health care resource and factor concentrate. Thirdly, we estimated the health outcome of male patients with hemophilia A. Lastly, we used conditional logistic regression to compare the risk of arthropathy between patients with prophylaxis and patients with on-demand regimen. In this study, we used age and the different dosage group to match case and control. Results Firstly, we identified 1184 patients with hemophilia. The number of patients were 1040 in 2003 and increased to 1092 in 2015. The prevalence of patients with hemophilia was estimated 4.6 per 100,000 people, while male patients with hemophilia was estimated 7.3 per 100,000 male in 2015. The newborn incidence ranged from 1.9 to 10.3 per 100,000 newborn, while the male newborn incidence ranged from 3.6 to 19.5 per 100,000 male newborn. The number of deaths ranged from 5 to 12, and the standardized mortality ratio was1.8 in patients with hemophilia A and hemophilia B. In the second part, the total medical cost of male patients with hemophilia was 1.0 billion NTD to 3.3 billion NTD from 2003 to 2015. The median number of visits using factor concentrate in 2015 was 6 in PWHA and 7 in PWHB. The cost of factor concentrate and bypassing agents (Factor VII and aPCC) accounted for 96% to 98% of total medical cost. In addition, the mean bleeding rate of patients with hemophilia A was 4.5 (SD 12.5)in 2015. The mean age of first diagnosis of arthropathy in patients with hemophilia A was 30.9 (SD 17.9)years old. In the nested case-control analysis, we included 512 cases and 512 controls with male gender and hemophilia A. We then divided these patients of both cases and controls into prophylaxis groups and on-demand groups. There were 79 and 433 cases in prophylaxis and on-demand groups. We used conditional logistic regression model to compare the odds between cases and controls. We found that the point estimate was 4.44(95% CI:=0.26-7.63). We further analyzed the subgroup study population whose were between 2 and 12 years old, and we found that the point estimate was 0.7 (95% CI:= 0.27-1.84) Conclusions The results of the epidemiologic data, utilization pattern and health outcome were consistent with previous studies. The findings indicated the average ages of patients were older by years, which implicated the increased life expectancy of persons with hemophilia. Therefore, age-related disorders will be the possible issue in the future.We found the use of by passing agents was increase by years, which warrants attention on the effectiveness and related issues. As time passed by, we found the use of factor concentrate and the medical cost increased by years, which highlights the importance for assessing the effectiveness or cost-effectiveness for the replacement therapy. Although there was no statistical significance, we found prophylaxis regimen tended to have better effectiveness than on-demand regimen in patients aged 2 to 12 years, which may imply that the early use of the prophylaxis regimen may pose some benefits in patients with hemophilia. Key words: Hemophilia, Coagulant factor, Arthropathy, Prophylaxis regimen, Nested case control study.