Inhibitor clinical burden of disease: a comparative analysis of the CHESS data

Abstract

Background: Patients with hemophilia and inhibitors generally face greater disease burden compared to patients without inhibitors. While raising awareness of relative burden may improve the standard of care for patients with inhibitors, comparative data are sparse. Analyzing data drawn from the Cost of Haemophilia across Europe - a Socioeconomic Survey (CHESS) study, the aim of this study was to compare the clinical burden of disease in patients with severe hemophilia with and without inhibitors. Hemophilia specialists (N = 139) across five European countries completed an online survey between January-April 2015, providing demographic, clinical and 12-month ambulatory/secondary care activity data for 1285 patients. Patients with hemophilia who currently presented with inhibitors and those who never had inhibitors were matched on baseline characteristics via propensity score matching. Outcomes were compared between the two cohorts using a paired t-test or Wilcoxon signed-rank or McNemar's test.

Results: The proportion of patients who currently presented with inhibitors was 4.5% (58/1285). Compared to PS-matched patients without inhibitors, patients with inhibitors experienced more than twice the mean annual number of bleeds (mean ± standard deviation, 8.29 ± 9.18 vs 3.72 ± 3.95; p < .0001) and joint bleeds (2.17 ± 1.90 vs 0.98 ± 1.15; p < .0001), and required more hemophilia-related (mean ± standard deviation, 1.79 ± 1.83 vs 0.64 ± 1.13) and bleed-related hospitalizations (1.86 ± 1.88 vs 0.81 ± 1.26), hemophilia-related consultations (9.30 ± 4.99 vs 6.77 ± 4.47), and outpatient visits (22.09 ± 17.77 vs 11.48 ± 16.00) (all, p < .001). More than one-half (53.5%) experienced moderate/severe pain necessitating medication compared to one-third (32.8%) of patients without inhibitors (p = .01).

Conclusions: Patients with hemophilia and inhibitors exhibited greater clinical burden and higher resource utilization compared to their peers without inhibitors. Strategies for improving the standard of care may alleviate burden in this population.

Keywords: Disease burden; Hemophilia; Inhibitors.

Fig. 1

Physician-reported chronic hemophilia-pain by severity for PS-matched patients with and without inhibitors in CHESS study^a. ^aPatients with current inhibitors were matched to patients who had never developed an inhibitor based on demographics (age, BMI, race) and comorbidity status using propensity scores stratified by hemophilia type. Matching was performed using a preset caliper size of 0.035 to maintain the maximum sample size using the smallest caliper width. ^bP-value refers to the difference in the proportion of patients with moderate to severe pain between cohorts and was derived from the McNemar’s test for categorical variables; p < .05 indicates statistical significance. Abbreviations: BMI, body mass index; CHESS, Cost of Haemophilia across Europe – a Socioeconomic Survey; PS, propensity score

Fig. 2

HRU frequency over 12 months for PS-matched patients with and without inhibitors in CHESS study^a. ^a‘N’ pertains to number of patients in each cohort after PS-matching. Patients with current inhibitors were matched to patients who had never developed an inhibitor based on demographics (age, BMI, race) and comorbidity status using propensity scores stratified by hemophilia type. Matching was performed using a preset caliper size of 0.035 to maintain the maximum sample size using the smallest caliper width. ^bP-values were derived from a paired t-test or Wilcoxon signed rank test for continuous post-match variables; p < .05 indicates statistical significance. Abbreviations: BMI, body mass index; CHESS, Cost of Haemophilia across Europe – a Socioeconomic Survey; HRU, health resource utilization; PS, propensity score; SD, standard deviation