A Descriptive Comparison of Disease Burden Between Hemophilia Patients with and without Inhibitors: Data from the CHESS Study

Introduction: The development of inhibitors is the most serious complication associated with the treatment of hemophilia. Prophylaxis remains the standard of care among non-inhibitor patients but the majority of inhibitor patients are managed on-demand. While it is generally accepted that inhibitor patients face a higher disease burden compared to non-inhibitor patients, limited comparative data exist in the literature.

Objective: This study compares disease burden between inhibitor and non-inhibitor patients.

Methods: Data were drawn from the Cost of Haemophilia across Europe - a Socioeconomic Survey (CHESS) study with data collected from January to April 2015. CHESS was developed as the first comprehensive, 'bottom-up' cost-of-illness study in severe hemophilia A & B (factor level <1%, over 18 years old) across five European countries (EU5): France, Germany, Italy, Spain, and the United Kingdom. A cross-section of 139 hemophilia specialists provided demographic and clinical information and retrospective 12-month ambulatory and secondary care activity for 1,285 patients via an online survey. Patient-reported health-related quality of life (QOL) was assessed via the EQ-5D. Impact on productivity was assessed based on self-reported number of days missed from work. This analysis was restricted to patients who currently had inhibitors and those who never had inhibitors. Analysis is descriptive and does not control for demographic, clinical, and other variables that could contribute to disease burden.

Results: Of the 1,285 surveyed patients, 58 (4.5%) currently had inhibitors and 1,091(84.9%) never had inhibitors. Mean (standard deviation; SD) age for the inhibitor and non-inhibitor patients was 41.9 (15) years and 35.2 (14.8) years, respectively. Mean (SD) number of bleeds for inhibitor and non-inhibitor patients was 8.3 (9.2) and 3.8 (5.4), respectively; 32.5% of bleeds for inhibitor patients were major versus 21.5% for non-inhibitor patients. Target joints were reported in 93.1% of inhibitor and 55.3% of non-inhibitor patients. Mean (SD) number of target joints for inhibitor and non-inhibitor patients was 2.2 (1.9) and 1 (1.3), respectively. Mean (SD) number of hemophilia-related consultations for inhibitor and non-inhibitor patients was 9.1 (5.1) and 6.5 (5.5), respectively. Mean hemophilia-related hospitalizations for inhibitor and non-inhibitor patients were 1.9 (1.9) and 0.6 (1.4), respectively. Moderate to severe pain was reported by 53.5% of inhibitor patients and 23.7% of non-inhibitor patients. Patients with inhibitors also reported lower QOL (i.e. mean (SD) EQ-5D: 0.5 (0.4) vs. 0.8 (0.3)) and more missed days from work (i.e. mean (SD) days: 30.1 (8.6) vs. 3.7 (24)) than non-inhibitor patients.

Conclusion: Data from the CHESS study suggest higher clinical and humanistic disease burden among hemophilia patients with inhibitors. Improving the standard of care for inhibitor patients, including the use of prophylaxis, may reduce the burden of disease in this population and improve health.