DEPENDENCE OF THE SEVERE HEMOPHILIA A – RELATED QUALITY OF LIFE IN CHILDREN FROM THE REGIMENS OF PROPHYLAXIS TREATMENT

Background: Fitusiran, an investigational RNA interference treatment for people with hemophilia A or B (PwH), with or without inhibitors, has shown dose-dependent lowering of antithrombin, increase in thrombin generation, and decrease in bleeding frequency in clinical trials. The novel mechanism of action and long pharmacodynamic effect enables once-monthly subcutaneous administration. This sustained hemostatic protection and less burdensome administration may improve patient-reported outcomes (PRO). Objective: To evaluate changes in PRO in terms of patient-relevant improvements in health-related quality of life (HRQoL) in PwH with inhibitors (PwHI) on prophylactic fitusiran treatment. Methods: Fitusiran was evaluated in a phase 1 dose-escalation study (NCT02035605) followed by a phase 2 open-label extension (OLE) study (NCT02554773) with monthly subcutaneous fixed doses of 50 mg or 80 mg. HRQoL was assessed using the Haem-A-QoL and the EuroQol 5 Dimensions (EQ-5D) questionnaires at baseline and at end of study in a cohort of 17 PwHI (Hemophilia A, n=15; Hemophilia B, n=2) from the phase 1 study. Results: Subjects previously treated on-demand or prophylactically had a mean (standard deviation [SD]) age of 34.6 (10.3) years and a mean (SD) number of bleeding episodes in the 6 months before baseline of 16.6 (10.7). Mean (SD) changes from baseline to end of study (day 84 or later) in Haem-A-QoL total (-9.2 [11.2]) and physical health (−12.3 [15.1]) domain scores suggest clinically meaningful improvement (lower scores indicate better HRQoL). Numeric reduction (i.e., improvement) in all other domains appeared to be dose-dependent (greater improvement in the 80 mg group) (Table 1). Changes in EQ-5D utility and EQ-VAS scores were not clinically meaningful. Further analyses in PwH with and without inhibitors from the phase 2 OLE will be presented. Conclusions: Fitusiran prophylaxis may improve HRQoL - particularly the Haem-A-QoL 'Physical health' domain (painful swelling, joint pain, pain with movement, difficulty walking, and time to get ready) as shown in a cohort of 17 PwHI . Additional analyses from ongoing OLE and phase 3 studies are planned to quantify the patient-relevant changes with fitusiran treatment in all hemophilia patients over time. Disclosures Von Mackensen: Sanofi, Bayer, Sobi, Chugai, Kedrion, Spark: Consultancy; Biotest, Sobi, CSL Behring: Honoraria; Novo Nordisk, Sobi: Research Funding. Chowdary:BioMarin: Honoraria; Bayer, CSL Behring, Freeline, Novo Nordisk, Pfizer and Sobi: Research Funding; Chugai, CSL Behring, Novo Nordisk, Pfizer, Roche, Sobi: Speakers Bureau; Bayer, Chugai, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, Sanofi, Shire (Baxalta), Sobi, Spark: Membership on an entity's Board of Directors or advisory committees. Mangles:Roche, Takeda, Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sobi, Octapharma, Novo Nordisk, Shire and Roche/Chugai: Other: travel funding. Yu:Sanofi: Other: was an employee and stockholder of Sanofi, at the time of study; Albireo Pharmaceuticals, Inc: Current Employment. Mei:Sanofi: Current Employment, Current equity holder in publicly-traded company. Andersson:Sanofi: Current Employment, Current equity holder in publicly-traded company. Dasmahapatra:Sanofi: Current Employment, Current equity holder in publicly-traded company.

Download Full-text

Health-related quality of life in a cohort of adult patients with mild hemophilia A

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2008.02929.x ◽

2008 ◽

Vol 6 (5) ◽

pp. 755-761 ◽

Cited By ~ 43

Author(s):

M. WALSH ◽

D. MACGREGOR ◽

S. STUCKLESS ◽

B. BARRETT ◽

M. KAWAJA ◽

...

Keyword(s):

Quality Of Life ◽

Hemophilia A ◽

Adult Patients ◽

Health Related Quality ◽

Related Quality ◽

Health Related

Download Full-text

Problem Joints and Their Clinical and Humanistic Burden in Children and Adults with Moderate and Severe Hemophilia a: CHESS Paediatrics and CHESS II

Blood ◽

10.1182/blood-2020-140306 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Paul McLaughlin ◽

Cedric Hermans ◽

Sohaib Asghar ◽

Tom Burke ◽

Francis Nissen ◽

...

Keyword(s):

Quality Of Life ◽

Research Funding ◽

Hemophilia A ◽

Joint Damage ◽

Severe Hemophilia ◽

Publicly Traded ◽

Hemophilic Arthropathy ◽

Joint Health ◽

Humanistic Burden

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.

Download Full-text

The Effects of Hemophilia on Socialization

Blood ◽

10.1182/blood.v124.21.5968.5968 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5968-5968

Author(s):

Aric Parnes ◽

Christine Mitchell ◽

Wentz Rachel ◽

Federico Campigotto ◽

Latoya Lashley ◽

...

Keyword(s):

Quality Of Life ◽

Hemophilia A ◽

Assessment Scale ◽

Health Related Quality ◽

Clotting Factors ◽

Patient Reported ◽

Related Quality ◽

Health Related ◽

Joint Assessment

Abstract BACKGROUND: Hemophilia, a congenital bleeding disorder resulting from a deficiency in clotting factors, typically VIII or IX, results in a propensity for severe, sometimes life-threatening or disabling, bleeds. Severity is determined by the baseline level of factor in plasma. Patients often require regular intravenous infusions of factor to prevent or treat bleeding episodes. Joint bleeds can lead to disabling arthropathy and past contamination of blood products has resulted in an epidemic of HIV and hepatitis in this community. We hypothesize that these issues may result in declines in quality of life, psychosocial well-being, and socialization (integration into society) and that socialization correlates with health-related quality of life (HR-QoL). METHODS: We developed and conducted a socialization survey and interview of patients age >20 with hemophilia A (n=14) or B (n=4) and their spouses/significant others (SSOs) (n=9). The interviews were analyzed using PROMIS (patient-reported outcomes measurement information system-29) domains. Patients completed surveys in health-related quality of life measures including both A36 Hemofilia-QoL and WHOQOL-BREF. Patients were also scored according to the Colorado Joint Assessment Scale and Karnofsky Performance Scale. With the exception of the Colorado Joint Assessment Scale, higher scores in all surveys reflect better health status. IRB approval and informed consent were obtained. RESULTS: 19 patients were enrolled, but one withdrew. Ages ranged from 24-78. Nine patients had severe hemophilia, 5 had moderate disease, and 4 had mild disease. Four patients did not have SSOs (22%); these included two severe and two moderate patients, one with HIV, and three with hepatitis C. Five SSOs declined participation. For the WHOQOL-BREF, patients reported overall quality of life in the physical domain an average score of 60 (13-94), standardized 0-100, 66 (31-100) in the psychological domain, 66 (31-100) in the social relationship domain, and 81 (44-100) in the environmental domain. For the A36 Hemofilia-QOL, the median total score was 94 (43-132) out of a possible 144 adding the following domains: Physical health, daily activities, joint damage, pain, treatment satisfaction, treatment difficulties, emotional functioning, mental health, and relationships and social activities. Colorado Joint Assessment Scale-QOL provided average scores of 6.1 out of 19 for ankles without gait and 8.3 out of 21 with gait, 4.2 for knees without gait, 6.3 with gait, and 3.6 for elbows. Preliminary analysis of interviews reflects social support as a common domain in both patients and SSOs and high reports of anxiety amongst SSOs compared to patients. CONCLUSION: This study characterizes quality of life by different measures in a hemophilia population and may affect their ability to integrate socially. The study employed established instruments as well as novel questionnaires and interview structures, although the latter have not been validated. Analysis of interviews is ongoing, but preliminary results point towards higher levels of anxiety in SSOs compared to patients. Both health-related-QoL and disease severity appear to be associated with domains of socialization. Patients with more severe disease may be less likely to have SSOs. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Factor VIII Intron 22 Inversion Screening of Newborn Males for Hemophilia A: A Cost-Effectiveness Study

Blood ◽

10.1182/blood.v116.21.734.734 ◽

2010 ◽

Vol 116 (21) ◽

pp. 734-734

Author(s):

John W. Luiza ◽

Margaret V. Ragni ◽

Robert F. Sidonio ◽

Kenneth J Smith

Keyword(s):

Quality Of Life ◽

Cost Effectiveness ◽

Factor Viii ◽

Hemophilia A ◽

Severe Hemophilia ◽

Pcr Screening ◽

Intron 22 Inversion ◽

Screening Cost ◽

The Cost

Abstract Abstract 734 Background: Severe hemophilia A is an X-linked congenital bleeding disorder occurring in 1:5,000 male births. Among neonates with severe hemophilia A, failure to recognize hemophilia and associated bleeding may result in severe blood loss anemia from circumcision, central nervous system (CNS) bleeding during the birth process or with head trauma and associated neurologic sequelae, and unrecognized joint bleeding that, when recurrent, increases the risk of joint damage which may lead to chronic disability. In at least one-third of cases, the disease arises as a spontaneous mutation: yet, even among the two-thirds with a family history, most carriers do not undergo carrier testing or prenatal diagnosis, leaving only a minority in whom cord blood screening is performed. About half of newborns with severe hemophilia A have a factor VIII (F.VIII) intron 22 inversion mutation, readily detected by PCR screening. We, therefore, sought to determine the effects of newborn screening by F.VIII intron 22 inversion PCR on early diagnosis in children with severe hemophilia A, specifically, on prevention of early life bleeding and associated cost, morbidity, and quality of life. Methods: We constructed a decision tree model to evaluate the cost effectiveness of newborn F.VIII intron 22 screening for severe hemophilia A. We assumed all newborn males were tested as part of screening, and that treatment modifies the likelihood of bleeding but not bleeding associated morbidity. Rates of major and minor CNS, joint, and procedural/surgical bleeding, including circumcision, morbidity and mortality, cost, and quality of life utilities were obtained from the literature. We assumed the cost of intron 22 PCR testing to be $3.00 per newborn male, that test results were available within 2 days of screening, and that clotting factor was infused prior to procedures and at the first sign of joint bleeding or head trauma. The probability of severe bleeding requiring hospitalization or red blood cell transfusion was estimated to be 5% or less in children with severe hemophilia A. The cost of F.VIII concentrate was based on the average wholesale price, and transfusion and hospitalization costs were based on local data. Outcomes included medical costs for each bleeding event, effectiveness measured as quality-adjusted-life-years (QALY), and the incremental cost-effectiveness ratio (ICER) over the first two years of life. Sensitivity analysis was used to test the robustness of analysis results. Results: Compared to no screening, screening for hemophilia had an ICER of $96,918/QALY, a value considered economically reasonable. Results were sensitive to variation of screening cost and overall detection of hemophilia A by PCR screening (base case 50%). Effects of varying both these parameters in a two-way sensitivity analysis are shown in the Figure. Using a $100,000 per QALY cost-effectiveness criterion over the depicted ranges for both parameters, screening was favored if screening cost ≤$3 or if ≥56% of all newborns with hemophilia A were detected by screening. Conclusion: It is cost effective to perform factor VIII intron 22 PCR screening to identify severe hemophilia A in newborn males in order to prevent bleeding morbidity, if the cost of the test does not exceed $3.00. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

PSY47 Evaluating the Cross-over Effect on Health-related Quality of Life in a Randomized Cross-over Study of Hemophilia-A Patients

Value in Health ◽

10.1016/j.jval.2011.08.1019 ◽

2011 ◽

Vol 14 (7) ◽

pp. A418-A419

Author(s):

H. Jo ◽

A. Gringeri ◽

C. Leissinger ◽

L. Mantovani ◽

P. Cortesi ◽

...

Keyword(s):

Quality Of Life ◽

Hemophilia A ◽

Health Related Quality ◽

Related Quality ◽

Health Related ◽

The Cross

Download Full-text

Health status and quality of life in patients with severe hemophilia A: A cross-sectional survey

Hematology Reports ◽

10.4081/hr.2019.7894 ◽

2019 ◽

Vol 11 (2) ◽

Cited By ~ 1

Author(s):

Majid Davari ◽

Zahra Gharibnaseri ◽

Roya Ravanbod ◽

Abolfazl Sadeghi

Keyword(s):

Quality Of Life ◽

Hemophilia A ◽

Clinical Information ◽

Cross Sectional Study ◽

Adult Patients ◽

Severe Hemophilia ◽

Cross Sectional Survey ◽

Cross Sectional ◽

The Mean

Among different groups of hemophiliacs, those suffering from Severe Hemophilia A (SHA) are most vulnerable to the complications of the disease. This study investigated the Health-Related Quality of Life (HR-QoL) among adult patients with SHA. A cross-sectional study was designed to gather demographic and clinical information from adult patients with SHA. Patients with inhibitors were excluded. The remaining were asked to complete the HR-QoL questionnaire after being examined for joint health using the Hemophilia Joint HealthScore (HJHS). The HR-QoL and joint conditions were measured in 38 patients. The mean EQ-5D value scores were 0.46 (SD=0.23) while the mean Visual Analogous Scale score was 50 (SD=18.7). The clinical examination of patients indicated that the HJHS were as follows: eight patients had a score of 55-75, 12 patients had a score of 40-55, 7 of them (25-40) and 11 patients had a score of 10-25. The results obtained from this study showed that HR-QoL in hemophilia patients was considerably low. Pain, anxiety/depression, and motion limitations were the main causes of the disutility for these patients respectively.

Download Full-text