Abstract
Hemophilia is an X-linked inherited bleeding disorder characterized by a deficiency of coagulation factor VIII or IX, leading to recurrent bleeding and joint damage, and in severe cases, disability or death. While factor replacement therapy remains the cornerstone of treatment, the development of inhibitors in some patients significantly diminishes therapeutic efficacy, complicating management and increasing economic burden. Systematic investigations on the impact of inhibitor on treatment modalities and overall disease burden in Chinese hemophilia patients based on real-world data remain limited.
This study employed a cross-sectional questionnaire design, utilizing data collected via the “Hemophilia Home” mobile application developed by Beijing Hemophilia Home Rare Disease Care Center. Data from patients diagnosed with hemophilia up to December 31, 2022, were analyzed. A total of 543 patients were enrolled, including 110 individuals with inhibitors and 433 without inhibitors. The questionnaire encompassed demographics, clinical history, treatment modalities, healthcare resource utilization, costs, and health-related quality of life. Descriptive statistics and regression models were used to assess intergroup differences.
The mean age of participants was 26.0 ± 14.8 years, with 99.63% being male. No significant age or sex differences were observed between groups. Patients with inhibitors were more likely to have hemophilia A (94.55% vs. 86.37%, P = 0.018) and a higher prevalence of severe disease (93.64% vs. 76.56%, P < 0.001). Among patients over 30 years old, nearly 90% had varying degrees of disability, with 54.88% overall holding disability certificates. The mean annual bleeding rate was 32.39 ± 54.29 episodes, with patients with inhibitors experiencing more frequent bleeds, but the difference was not statistically significant (36.29 vs. 31.39, P = 0.399). Immune tolerance induction (ITI) therapy was associated with reduced bleeding frequency in patients with inhibitors (24.00 ± 27.84 episodes/year). Joint disease was reported in 73.48% of patients, with higher prevalence in the inhibitor-positive group (80.00% vs. 71.82%, P = 0.083), though surgical intervention was less frequent (19.09% vs. 32.33%, P = 0.007).
The average annual frequency of prophylactic treatment was 127.67 ± 57.64 episodes. However, the rate of prophylaxis usage was significantly lower in patients with inhibitors (54.55% vs. 81.99%, P < 0.001). Notably, patients with inhibitors received significantly higher per-weight doses of factor products for both prophylactic and on-demand treatments (33.76 IU/kg vs. 21.16 IU/kg, P < 0.001; 37.82 IU/kg vs. 28.04 IU/kg, P = 0.004, respectively).
The average annual per capita cost was CNY 520,415 ± 773,627, with direct medical expenses constituting 87.55% of total costs—primarily driven by medication. Patients with inhibitors bore significantly higher non-medical costs, including transportation (CNY 5,329 vs. 1,877, P < 0.001) and caregiver absenteeism (CNY 14,488.68 vs. 8,955.87, P = 0.005). HRQoL assessments indicated poor outcomes across the cohort, with patients with inhibitors scoring significantly lower on EQ-5D-5L (self-report: 0.472 vs. 0.575, P = 0.010; proxy-report: 0.481 vs. 0.597, P = 0.005) and SF-6Dv2 (0.377 vs. 0.459, P = 0.020). Particularly, greater impairments were observed in pain, mobility, and anxiety/depression domains.
In conclusion, the presence of inhibitors substantially exacerbates the complexity of hemophilia treatment, heightens disease and economic burdens, and significantly diminishes quality of life. Early intervention strategies, broader coverage of prophylactic regimens, and enhanced social support systems are urgently needed to improve the long-term prognosis of patients with inhibitors.
