• Evidence of a Hemophilia Employment Gap: Comparing Data from CHESS US+ and the 2019 Current Population Survey

      Asghar, Sohaib; Burke, Tom; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; O'Hara, Jamie (American Society of Hematology, 2020-11-05)
      INTRODUCTION Severe hemophilia A (<1% normal FVIII activity) and B (<1% normal FIX activity) are congenital bleeding disorders characterized by uncontrolled bleeding, either spontaneously or in response to trauma or surgery. Recent commentary has identified a number of patient-important and patient-relevant outcomes that have been understudied, namely the challenges faced by people living with hemophilia to participate in the labor force. The socio-economic impact of hemophilia is comparatively less well understood than clinical outcomes and therapy-related costs. Under-employment and under-utilization have long-term consequences to individuals' job prospects and psychosocial health, as well as an economic cost to the society. The objective of the analysis is to compare labor market participation, among people with severe hemophilia from the US and the general population. This analysis draws on household data derived from the 2019 Current Population Survey (CPS), and on patient-reported data from a patient-centric study conducted in 2019 of people with severe hemophilia, in the US: the 'Cost of Severe Hemophilia Across the US: A Socioeconomic Survey' (CHESS US+). METHODS A patient-centric framework informed the design of CHESS US+ a retrospective (12 months prior to study enrollment), cross-sectional dataset of adults with severe hemophilia in the US. Conducted in 2019, the study used a patient-completed questionnaire to collect data on patient-relevant clinical, economic, and humanistic outcomes. This analysis examines labor market participation (full-time, part-time, unemployed), and corresponding general population data derived from the 2019 Current Population Survey (CPS). Data on the general population were sourced from the 2019 CPS 'Employment status of the civilian noninstitutional population'. Persons 'not in the labor force' in the 2019 CPS and retired persons in CHESS US+ were not included in the analysis. We present data on the civilian labor force, in CHESS US+ and in the 2019 CPS. Results are presented as mean (standard deviation) or N (%). RESULTS Of 356 patients profiled in the CHESS US+ study, 97 (27%) had severe hemophilia B and 257 (73%) had severe hemophilia A. Mean age and weight (kg) of the cohort was 34.99 (12.15) and 85.71 (22.81), respectively. The labor force participation rates of non-retired people with severe hemophilia in CHESS US+ (N = 340) and the general population (161,458) are described in Table 1. Examining aggregate data on employment status observed a higher proportion of people with severe hemophilia in part-time employment (24.4% vs. 15.7%). Differences in the labor force participation of people living with severe hemophilia compared to the general population were most pronounced in the full-time employment rate and the unemployment rate. Compared to 80.7% of the general population (Table 1), only 53.5% of people with severe hemophilia in CHESS US+ had a full-time job. Moreover, the unemployment rate (Table 1) in the 2019 CPS compared with the rate observed in CHESS US+ (3.7% vs. 22.1%) provides a stark contrast in the employment experiences of people living with severe hemophilia relative to the general population. CONCLUSIONS This analysis of CHESS US+ illustrates the impact of severe hemophilia on labor force participation. People with severe hemophilia were more likely than the general population to be unemployed, or in part-time employment. A notable contrast was observed in the rate of full-time employment and unemployment, among the general population compared to people living with severe hemophilia. These data illustrate the need to quantify the impact of hemophilia using a holistic approach that considers the cost of involuntary illness-related part-time and unemployment. Disclosures Asghar: HCD Economics: Current Employment. Burke:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy; University of Chester: Current Employment. Misciattelli:Freeline: Current Employment, Current equity holder in publicly-traded company. Kar:Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan:HCD Economics: Current Employment; uniQure: Consultancy. O'Hara:F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.
    • Problem Joints and Their Clinical and Humanistic Burden in Children and Adults with Moderate and Severe Hemophilia a: CHESS Paediatrics and CHESS II

      McLaughlin, Paul; Hermans, Cedric; Asghar, Sohaib; Burke, Tom; Nissen, Francis; Aizenas, Martynas; Meier, Oliver; Dhillon, Harpal; O'Hara, Jamie (American Society of Hematology, 2020-11-05)
      Introduction Severe hemophilia A (SHA) is characterized by spontaneous (non-trauma related) bleeding episodes into the joint space and muscle tissue, leading to progressive joint deterioration and chronic pain. Chronic joint damage is most often associated with severe hemophilia, however more recent research has illustrated that people with moderate hemophilia A (MHA) also experience hemophilic arthropathy and functional impairment. The need to measure joint health in children as well as adults, is underscored by findings from the Joint Outcome Continuation Study, which found that FVIII prophylaxis was insufficient to protect joints from damage, from childhood through adolescence in severe HA (Warren et al., 2020). The objective of this analysis is to gain a more patient-centric understanding of the clinical, economic and humanistic burden associated with 'Problem Joints', a measure of joint morbidity developed in consultation with an expert panel to overcome limitations with existing measures, in people with MHA and SHA. Methods A descriptive cohort analysis was conducted, utilizing retrospective, cross-sectional real-world data from the 'Cost of Haemophilia in Europe: a Socioeconomic Survey' (CHESS Paeds and CHESS II), studies of adult and pediatric persons with hemophilia. The analysis population is comprised of children (17 and below) with MHA or SHA in CHESS Paeds, and adults aged 20 and over with MHA or SHA in CHESS II. To account for the possibility that persons aged 18 or 19 in CHESS II may have participated in CHESS Paeds, these individuals were excluded from the analysis. Physician-reported clinical outcome data and patient/caregiver-reported quality of life were analyzed. A problem joint (PJ) is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e. chronic synovitis and/or hemophilic arthropathy). Analyses were stratified by number of PJs: none, 1 PJ, and 2+ PJs. We report retrospective data of the 12 months prior to study enrollment, on annualized bleeding rate (ABR), prevalence of target joints (TJ), as defined by the International Society on Thrombosis and Haemostasis, and EQ-5D-/5L/Y/Proxy score. Results are presented as mean (standard deviation) or N (%). Results Among 785 participants (N = 464 SHA; N = 321 MHA) in CHESS Paeds, mean age and BMI were 10.33 (4.63) and 22.50 (17.07), respectively. Of 493 participants (aged 20 and above) in CHESS II (N = 298 SHA; N = 195 MHA), the mean age and BMI were 38.61 (14.06) and 24.55 (2.92), respectively. Current inhibitor to FVIII replacement was more prevalent in children than in adults (10% vs. 5%). In CHESS II, approximately 40% of people with MHA and 49% with SHA had one or more PJs, respectively [1 PJ (23% vs. 28%); 2+ PJs (16% vs. 21%)]. In CHESS Paeds, approximately 14% of children with MHA and 18% with SHA had at least one PJ, respectively [1 PJ (9% vs. 14%); 2+ PJs (5% vs. 3%)]. TJs were less prevalent with MHA in comparison to SHA, in both adults (24% vs. 45%) and children (13% vs. 22%). Clinical burden was higher among both children and adults with PJs compared to those with no PJs. ABR correlates with the number of PJs, in those with MHA and SHA in CHESS II (Figure 1). Similarly, PJs were associated with higher ABR across MHA and SHA in CHESS Paeds (Figure 2). Hemophilia-related hospitalizations were higher in both adult and pediatric participants with PJs. In CHESS II, MHA with no PJs had fewer [0.73 (1.23)] hospitalizations compared to having those with 1 PJ [1.38 (1.11)] or 2+ PJs [1.28 (1.25)]. Similarly, children with MHA with 2+ PJs had 1.60 (1.92) hemophilia-related hospitalizations, compared to 1.38 (1.92) with 1 PJ and 0.71 (1.14) with no PJs. PJs were associated with impaired quality of life. In CHESS II, MHA and SHA EQ-5D-5L values in persons with no PJs were 0.81 (0.19) and 0.79 (0.18), respectively, compared to 0.65 (0.16) and 0.62 (0.23) with 1 PJ, and 0.65 (0.14) and 0.51 (0.33) in with 2+ PJs. A similar trend was observed in EQ-5D-Y and EQ-5D-proxy scores in CHESS Paeds. Conclusions Data from CHESS Paeds and CHESS II demonstrate an association between chronic joint damage, as measured by the 'problem joint' definition, and worsening clinical and quality of life outcomes, across both MHA and SHA. Further analyses will seek to expand upon the initial results presented here, to investigate the wider elements of burden associated with compromised long-term joint health. Disclosures McLaughlin: BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Hermans:Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; WFH: Other; EAHAD: Other; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; LFB: Consultancy, Speakers Bureau. Asghar:HCD Economics: Current Employment. Burke:HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Nissen:GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Aizenas:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Dhillon:HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara:F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.
    • Prophylactic Treatment in People with Severe Hemophilia B in the US: An Analysis of Real-World Healthcare System Costs and Clinical Outcomes

      Noone, Declan; Pedra, Gabriel; Asghar, Sohaib; O'Hara, Jamie; Sawyer, Eileen K; Li, Nanxin (Nick) (American Society of Hematology, 2019-11-13)
      Introduction The treatment paradigm for people with severe hemophilia B in the US typically involves prophylaxis with factor IX (FIX) replacement therapy, the primary aim of which is to provide sufficient FIX levels to reduce the frequency of bleeding events. The clinical benefits of FIX prophylaxis are well understood, however the cost of FIX products as well as costs associated with healthcare resource utilization present a significant burden to the healthcare system. Substantive costs may also accrue in patients who continue to bleed while on prophylaxis, due to the impact on both short and long-term joint-related outcomes. In the absence of existing data in the US, the 'Cost of Hemophilia Across the USA: a Socioeconomic Survey' (CHESS US) study was conducted to establish a population-based estimate of the real-world US healthcare system burden associated with severe hemophilia. Using data drawn from the CHESS US study, this analysis examines the real-world healthcare system costs and clinical outcomes of people with severe hemophilia B on FIX prophylaxis. Methods CHESS US, a retrospective, cross-sectional dataset of adults with severe hemophilia in the USA, gathered information on patient cost via a patient record form. Data on the following parameters are included in this analysis: FIX consumption, annualized bleeding rate (ABR), the presence of one or more chronically damaged joints ("problem joint"), as well as costs associated with annual (prophylactic) factor consumption and hospitalizations (i.e., number of admissions, number of day cases, total inpatient days, and total intensive care unit [ICU] days). All variables report retrospective data of the 12 months prior to enrolment in the study. Results are presented as mean (± standard deviation) or N (%). Results In total, 132 of 576 patients profiled in the CHESS US study had severe hemophilia B. Among them, 77 patients were on FIX prophylaxis, of whom 44 patients reported FIX dosing regimen and were included in the current analyses. Among them, 20 patients were treated with conventional FIX and 24 patients with extended half-life (EHL) FIX products. The cohort has a mean age of 27.64 (± 11.05) and mean weight (kg) of 75.71 (± 13.41). In the last 12 months, the mean number of international units (IU) prescribed for FIX prophylaxis across the full cohort was 257,216 IU (± 213,591), with an associated annual cost of $610,966 (± $495,869). Among patients treated with conventional FIX, mean prescribed FIX was 287,141 IU (± 264,906) at an annual cost of $397,491 (± $359,788), while patients treated with EHL FIX reported a mean prescribed FIX of 232,278 IU (± 160,914) at an annual cost of $788,861 (± $529,258). The cohort reported a mean ABR of 1.73 (± 1.39); 8 (18%) were reported to have a target joint meeting the International Society on Thrombosis and Haemostasis (ISTH) definition; and 11% were reported to have had at least one chronically damaged joint (i.e., problem joint). Healthcare resource utilization associated with bleed events were reported as follows: hospital admissions days [0.18 (± 0.62)]; inpatient days [0.34 (± 1.22)]; and ICU days [0.23 (± 0.86)]. The direct medical cost to the healthcare system was $2,885 (± $7,857; excluding FIX cost) and $614,886 (± $498,839; including FIX cost). Discussion Data from the CHESS US study showed substantial costs and resource utilization among patients with severe hemophilia B receiving FIX prophylaxis, of which the cost of FIX replacement therapy constituted most of the total cost to healthcare system. Although the ABR observed in the analysis population was low, bleed-related hospitalizations comprised a significant non-drug cost to the healthcare system. A proportion of patients also still experienced joint arthropathy. Such substantial clinical and economic burden highlights that unmet needs remain in patients with severe hemophilia B on FIX prophylaxis in the US. Disclosures Noone: HCD Economics: Employment. Pedra:HCD Economics: Employment. Asghar:HCD Economics: Employment. O'Hara:HCD Economics: Employment, Equity Ownership. Sawyer:uniQure Inc.: Employment. Li:uniQure Inc.: Employment.
    • Understanding minimum and ideal factor levels for participation in physical activities by people with haemophilia: An expert elicitation exercise.

      Martin, Antony P; orcid: 0000-0003-4383-6038; Burke, Tom; Asghar, Sohaib; Noone, Declan; Pedra, Gabriel; orcid: 0000-0002-2023-5224; O'Hara, Jamie (2020-04-08)
      The benefits of physical activity (PA) for people with haemophilia (PWH) may include improvements in joint, bone and muscle health. However, the factor VIII activity level required to avoid a bleeding episode associated with PA is unknown. To elicit the opinion of clinical experts on the minimum level and ideal factor VIII activity ('level') required to avoid a bleeding episode during participation in different types of PA for PWH. Based on the 2017 National Hemophilia Foundation PA descriptions, clinical experts estimated a minimally acceptable and an ideal factor level at which a bleed could be avoided. The uncertainty around estimates was quantified using an approach to construct a probability distribution to represent expert opinion. Minimum and ideal factor level increased with higher risk PA, whether or not joint morbidity was present, as did the experts' uncertainty in their estimates (ie the range between lowest and highest estimates for minimum and ideal levels). Mean minimum levels ranged from 4% to 48% for low to high risk for people without joint morbidity, and from 7% to 47% for those with joint morbidity. For ideal factor levels, corresponding figures were 9%-52% and 12%-64%, respectively. To support a patient-centric outcome, expert opinion indicates that the clinical norm of 0.01 IU/mL (1%) trough level is insufficient. It is anticipated that introducing a more targeted approach to meet the needs of patients who are increasingly physically active will benefit patients further in addition to recent treatment advances. [Abstract copyright: © 2020 John Wiley & Sons Ltd.]