Effectiveness of Prophylactic Coagulation Factor Replacement Therapy in Patients with Severe Hemophilia A in Taiwan – A Population-Based Study

Abstract

Purpose

Taiwan launched reimbursement of prophylactic coagulation factor replacement therapy (CFRT) for patients with severe hemophilia type A (severe PWHA) in 2014. However, since then, the effectiveness of prophylactic CFRT in real-world practice has not been evaluated thoroughly. This study aimed to evaluate the effectiveness of prophylactic CFRT in severe PWHA cases on the outcome of bleeding risks.

Patients and Methods

We included male, severe PWHA cases from a nationwide, population-based database in Taiwan. Given that the database lacked details of the dosing regimen for prophylactic CFRT, we applied group-based trajectory modeling using the proportion of days covered (PDC) by CFRT from 2014 to 2015 in order to classify patients. A high PDC level corresponded to a greater proportion of time under CFRT, thus implying that the patient was probably receiving prophylactic therapy. We followed up patients from January 01, 2016 until occurrence of any bleeding events, death or December 31st 2017.

Results

We identified a total of 420 severe PWHA and classified them into high- (n = 88), medium- (n = 181) and low- (n = 151) PDC groups. The mean (±SD) PDC values of the three groups were 0.78 (±0.1), 0.40 (±0.1) and 0.12 (±0.1), respectively. Using Cox regression models with propensity score adjustment, we found patients with medium- (hazard ratio: 0.69; 95% CI: 0.56–0.89) or high-PDC (0.45; 0.36–0.68) under CFRT had reduced risks of any bleeding, compared to the low PDC group.

Conclusion

The findings demonstrated the effectiveness of prophylactic CFRT in the prevention of bleeding events in real-life severe PWHA.

Keywords:

• hemophilia
• coagulation factor replacement therapy
• prophylaxis
• proportion of days covered

Abbreviations

CFRT, Coagulation factor replacement therapy; CI, Confidence interval; CIC, Catastrophic Illness Certificates; FVIII, Coagulation factor VIII; GBTM, Group-based trajectory modeling; NHID, National Health Insurance Database; PDC, Proportion of days covered; PWHA, Patients with hemophilia A; SD, Standard deviation; WFH, World Foundation of Hemophilia.

Data Sharing Statement

Data are not available due to legal restrictions for privacy protection of susceptible populations under the regulations of Taiwan.

Ethics Approval and Consent to Participate

This study was conducted in accordance with the ethical standards of the Institutional Review Board and the Declaration of Helsinki. Research ethics approval was given by the IRB of National Cheng Kung University Hospital (ID B-ER-108-390), whereby the IRB waived the written informed patient consent requirement due to the retrospective nature of the study design and because all individual identifiers were encrypted and thus not personally identifiable.

Acknowledgments

We are grateful to Health Data Science Center, National Cheng Kung University Hospital for providing administrative and technical support. Miyuki Hsing-Chun Hsieh and Shyh-Shin Chiou are co-first authors for this study.

Author Contributions

All authors made a significant contribution to the work reported, whether in conception, study design, execution, acquisition of data, analysis or interpretation. They took part in drafting, revising or critically reviewing the article; they all gave final approval of the version to be published and agreed on the journal to which to submit the article. All authors have agreed to be held accountable for all aspects of the work.

Disclosure

The authors had received research funding from Takeda Pharmaceutical Company and Ministry of Science and Technology. However, the funders had no roles in study design, analysis or interpretation. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study received a grant from Takeda Pharmaceutical Company and Ministry of Science and Technology (107-2320-B-006-070-MY3), which had no role in design, conduct, or data interpretation of the study.