The Impact of Pharmacokinetic-Guided Prophylaxis on Clinical Outcomes and Healthcare Resource Utilization in Hemophilia A Patients: Real-World Evidence from the CHESS II Study.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-01-01, epub 2022-09-19Publication status: PublishedBackground: Using a pharmacokinetic (PK)-guided approach to personalize the dose and frequency of prophylactic treatment can help achieve and maintain targeted factor VIII (FVIII) trough levels in patients with hemophilia A. Objective: Investigate clinical and healthcare resource use outcomes in patients with hemophilia A treated with or without PK-guided prophylaxis using data from the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) II database. Methods: CHESS II was a cross-sectional, retrospective, burden-of-illness study incorporating data from eight European countries. Patients were eligible for this analysis if they were male, ≥18 years of age, and diagnosed with congenital hemophilia A of any severity. The clinical endpoints included annualized bleeding rate (ABR), presence and number of problem/target joints, and occurrence of joint surgeries. Healthcare resource utilization endpoints included the number of hematologist consultations and bleed-related hospitalizations or emergency department admissions. Data from November 2018 to October 2020 were included and were stratified according to treatment regimen and use of PK-guided dosing. Results: Altogether, 281 patients on prophylaxis had available FVIII trough level data. Mean (SD) age was 35.7 (13.8) years. A specific FVIII trough level was targeted in 120 (42.7%) patients and 47 (39.2%) received PK-guided dosing. Patients receiving PK-guided dosing had a mean (SD) ABR of 2.8 (2.1) and target joint number of 0.5 (0.7), compared with 3.9 (2.7) and 0.9 (1.4), respectively, for patients receiving non-PK-guided treatment. The mean (SD) number of hematologist consultations was 7.1 (5.3) for patients receiving PK-guided dosing versus 10.7 (5.7) for those who were not. A higher proportion of patients in the non-PK-guided group required hospitalization during their lifetime compared with the PK-guided group.ConclusionThis analysis of real-world data suggests that PK-guided dosing for prophylaxis has a beneficial impact on clinical and healthcare resource utilization outcomes in patients with hemophilia A

The impact of bleeding event frequency on health-related quality of life and work productivity outcomes in a European cohort of adults with haemophilia A: insights from the CHESS II study

Background: Haemophilia A carries a substantial healthcare burden, affecting health-related quality of life (HRQoL). The Cost of Haemophilia in Men: a Socioeconomic Survey II (CHESS II), a retrospective real-world study, characterised the burden of haemophilia and its impact on HRQoL and work productivity. The current analysis explored the impact of bleeding events on HRQoL and work productivity in Europe. This analysis focused on data collected from males aged 18 to 64 years with haemophilia A without inhibitors who were receiving replacement factor products or a monoclonal antibody and were not participating in a clinical trial at the time of study recruitment. Descriptive statistics were analysed using scores from EuroQoL’s EQ-5D-5L index and EQ-VAS analogue scale and the Work Productivity and Activity Index Specific Health Problem (WPAI:SHP) percentage scores stratified by the number of annual bleeding events (ABs) 0, 1, 2, 3–4, or ≥ 5. Results: Of 918 males with haemophilia A in CHESS II, 318 met inclusion criteria and had data available for HRQoL measures; mean age (SD) was 33.8 (12.1) years and 96% were White. Mean (SD) ABs of 2.7 (2.9) occurred over the preceding 12 months: 20% had 3 or 4 ABs; 17% had ≥ 5 ABs. Mean EQ-5D-5L index scores for patients with 0, 1, 2, 3–4, or ≥ 5 ABs were 0.92, 0.76, 0.76, 0.71, and 0.56, respectively. Mean (SD) EQ-VAS scores were 86.9 (13.6), with 0 ABs versus 69.5 (19.1) for 3 or 4 ABs and 61.2 (17.2) for ≥ 5 ABs. Mean percentage of overall work productivity loss on the WPAI:SHP questionnaire ranged from 9.70 to 0 ABs to 47.65 for ≥ 5 ABs. Conclusions: In this European sample of adult men with haemophilia A, HRQoL and work productivity scores were lower among those reporting more AB events. Bleeding burden appears to affect HRQoL and productivity; however, this cross-sectional analysis limits the ability to draw firm conclusions on causality.Acknowledgements: Medical writing and editorial support were provided Marion James, PhD, CMPP, of Engage Scientific Solutions (Horsham, UK) and by Anna Battershill, MSc, and Michael Morren, RPh, MBA, of Peloton Advantage, LLC, an OPEN Health company, and funded by Pfizer. The authors thank Leona Markson (Pfizer Inc, Collegeville, PA, USA) for her critical review of the early drafts of this manuscript.Pfizer; doi: http://dx.doi.org/10.13039/100004319; Grant(s): Pfize

Exploring the relationship between condition severity and health-related quality of life in people with haemophilia A across Europe: a multivariable analysis of data from the CHESS II study

Background: Haemophilia A (HA; Factor VIII deficiency) is a congenital X-linked bleeding disorder characterized by trauma-related or spontaneous bleeding events, most notably arising within the intraarticular space and resulting in chronic inflammation and degeneration of affected joints. Endogenous clotting factor activity relative to normal levels determines the severity of HA symptoms, as mild (> 5–40%), moderate (1–5%), or severe (< 1%). Within the current environment of rapid evolution in HA management, we seek to understand the interplay of condition severity and health-related quality of life (HRQoL) to characterise and differentiate unmet needs among people with HA (PwHA). Methods: A generalised linear regression model (GLM) was developed to explore the relationship between HA severity and EQ-5D-5 L index score from adult HA patients sampled in the “Cost of Haemophilia across Europe – a Socioeconomic Survey II” (CHESS II) cross-sectional, retrospective burden of illness study among adults with hereditary haemophilia A or B from eight European countries. HA patients of any severity with no active inhibitors during the 12 months prior to data capture and a completeEQ-5D-5 L response were included. A base GLM model was specified with covariates for demographic and clinical characteristics (age, body mass index, country, employment, HA severity, annual bleeding rate, problem joints, and chronic pain). Results: Of 381 evaluable patients, 221 (58.0%) had severe HA, 96 (25.2%) had moderate HA, and 64 (16.8%) had mild HA. Among the covariates included in the GLM model and after controlling for haemophilia-related outcomes, a significant association was observed between mild HA and higher EQ-5D-5 L index score (average marginal effects, 0.084; p = 0.016) relative to severe HA. Patient country of residence and magnitude of HA-related chronic pain were also associated with significant differences in index scores, with the latter showing a negative relationship with HRQoL outcomes. Conclusions: Condition severity and chronic pain are significant predictors of HRQoL in PwHA. Durable bleeding protection and effective management of chronic pain have the potential to address unmet treatment needs in this population.Unfunde

Economic and Humanistic Burden of Moderate and Severe Hemophilia A and B in Spain: Real-World Evidence Insights from the CHESS II Study

Background: Hemophilia is a congenital disorder characterized by deficiency or absence of clotting factor VIII in hemophilia A (HA) or clotting factor IX in hemophilia B (HB), resulting in frequent, repeated, and prolonged spontaneous or traumatic bleeding into joints or soft tissue. Severity is classified by the patient’s baseline level of clotting factor activity as mild (&gt;5%-40%), moderate (1%-5%), or severe (&lt;1%). In Spain, there is limited information on the societal economic burden of disease. Objective: To estimate the economic and humanistic burden of disease in adult patients with non-inhibitor moderate and severe HA and HB in Spain. Methods: Spanish data from the CHESS II study (2018-2020) on patients’ clinical characteristics, health-related quality of life (HRQoL) and hemophilia-related healthcare resource utilization were analyzed. Economic burden was determined by estimating condition-related annual per-patient direct (medical and nonmedical) and indirect costs, stratified according to hemophilia type and severity and presented as 2022 Euros. HRQoL was assessed via the EQ-5D-5L. Results: Of 341 patients in the Spanish CHESS II cohort, 288 patients met the inclusion criteria: 181 had HA (37% [n = 66] moderate and 63% [n=115] severe) and 107 had HB (26% [n = 28] moderate and 74% [n = 79] severe). Mean annual direct cost was higher in HB than in HA, and higher in severe than in moderate patients, resulting in an annual cost/patient of €17 251 (moderate HA), €17 796 (moderate HB), €116 767 (severe HA) and €206 996 (severe HB). The main direct cost component in all groups except moderate HA was factor replacement therapy. Mean per-patient indirect cost was €4089 (moderate HA), €797 (moderate HB), €8633 (severe HA) and €8049 (severe HB). Finally, the mean total cost (direct and indirect) for moderate and severe patients were €91 017 (HA) and €163 924 (HB). EQ-5D-5L [SD] scores were lower in patients with severe HA (0.77 [0.18]) and severe HB (0.70 [0.22]) compared with patients with moderate HA (0.81 [0.15]) and moderate HB (0.86 [0.17]). Conclusions: Independently of the type of hemophilia, greater condition severity was associated with increased costs and a decrease in HRQoL

Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-02-01, epub 2022-02-02Publication status: PublishedFunder: Albireo Pharma, Inc.BackgroundProgressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included.ResultsThe PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30-49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient's PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days).ConclusionsThe PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances

Real-world clinical and psychosocial outcomes among people with mild or moderate haemophilia A treated on-demand in the Italian CHESS II cohort: a real-world data analysis

© 2024 Giancarlo Castaman et al., published by SciendoBackground: The burden of severe haemophilia A (HA) has been studied extensively owing to the higher bleeding frequency and associated treatment requirements, leaving a clear unmet need for research focused on the burden of mild and moderate HA. Aims: This study sought to characterise the clinical and psychosocial burden of mild and moderate HA in the Italian cohort of the CHESS II study. Methods: This was a retrospective analysis of clinical and psychosocial outcomes in a cohort of male adults (≥18 years old) with mild or moderate HA who participated in the cross-sectional CHESS II study (October 2019-November 2020). Treatment patterns, acute and chronic clinical outcomes and mental health indicators were collected via physician-completed forms. Psychosocial outcomes related to impact of HA on social activities, exercise, opportunities, and lifestyle were collected via a participant self-complete questionnaire. All results were reported descriptively. Results: A total of 113 people with haemophilia A (PwHA) were included, 79 (70%) with moderate HA and 34 (30%) with mild HA, with mean age of 41.4 and 36.6 years, respectively. No one in the sample was receiving a prophylaxis at the time of data capture, with factor VIII use in the 12 months prior reported in 30% and 29% of moderate and mild PwHA, respectively. Ninety-one PwHA (81%) experienced ≥1 bleeding event in the preceding 12 months. People with moderate HA had higher mean annual bleed rate (2.9 vs. 1.1, respectively) and higher prevalence of chronic pain (74% vs. 35%), anxiety (20% vs. 12%), and/or depression (15% vs. 3%). Target joints were reported in 22% and 12% of moderate and mild PwHA, and problem joints in 51% and 12%, respectively. Of 113 participants, 44 (39%) completed the self-complete form (moderate HA, 57%; mild HA, 43%). Overall, 40% vs. 10% of those with moderate vs mild HA reported reducing or giving up social activities, 44% vs. 21% reducing or giving up exercise, 36% vs. 26% missing out on opportunities, and 48% vs. 26% reported HA impacted their lifestyle. Conclusion: Moderate PwHA from the Italian CHESS II cohort appeared to have greater clinical morbidity and lifestyle impact than mild PwHA. Psychosocial outcomes were also worse among moderate PwHA, but significant burden was also observed among mild PwHA. These findings, and the absence of prophylactic treatment in the sample examined, highlight that improving management for potentially undertreated mild/moderate PwHA may aid the avoidance long-term clinical morbidity and negative psychosocial impact.Acknowledgements: This paper reports a retrospective study in which no human participants or animals are directly involved. Medical writing/editorial support was provided by Jeff Frimpter, MPH, funded by HCD Economics. This analysis was funded by Roche SpA, Rozzano, Italy. Roche were involved in the analysis conception, design and interpretation of results, as well as drafting and submission of the manuscript. EFG, TB1, and TB2 are employees of HCD Economics. LS, RT and SB are employees of Roche SpA

Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study

From Springer Nature via Jisc Publications RouterHistory: received 2021-11-02, accepted 2022-01-16, registration 2022-01-18, pub-electronic 2022-02-02, online 2022-02-02, collection 2022-12Publication status: PublishedFunder: Albireo Pharma, Inc.Abstract: Background: Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included. Results: The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30–49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient’s PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days). Conclusions: The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances

The Impact of Pharmacokinetic-Guided Prophylaxis on Clinical Outcomes and Healthcare Resource Utilization in Hemophilia A Patients: Real-World Evidence from the CHESS II Study.

From PubMed via Jisc Publications RouterHistory: received 2022-02-23, accepted 2022-08-30Publication status: epublishUsing a pharmacokinetic (PK)-guided approach to personalize the dose and frequency of prophylactic treatment can help achieve and maintain targeted factor VIII (FVIII) trough levels in patients with hemophilia A. Investigate clinical and healthcare resource use outcomes in patients with hemophilia A treated with or without PK-guided prophylaxis using data from the Cost of Haemophilia in Europe: A Socioeconomic Survey (CHESS) II database. CHESS II was a cross-sectional, retrospective, burden-of-illness study incorporating data from eight European countries. Patients were eligible for this analysis if they were male, ≥18 years of age, and diagnosed with congenital hemophilia A of any severity. The clinical endpoints included annualized bleeding rate (ABR), presence and number of problem/target joints, and occurrence of joint surgeries. Healthcare resource utilization endpoints included the number of hematologist consultations and bleed-related hospitalizations or emergency department admissions. Data from November 2018 to October 2020 were included and were stratified according to treatment regimen and use of PK-guided dosing. Altogether, 281 patients on prophylaxis had available FVIII trough level data. Mean (SD) age was 35.7 (13.8) years. A specific FVIII trough level was targeted in 120 (42.7%) patients and 47 (39.2%) received PK-guided dosing. Patients receiving PK-guided dosing had a mean (SD) ABR of 2.8 (2.1) and target joint number of 0.5 (0.7), compared with 3.9 (2.7) and 0.9 (1.4), respectively, for patients receiving non-PK-guided treatment. The mean (SD) number of hematologist consultations was 7.1 (5.3) for patients receiving PK-guided dosing versus 10.7 (5.7) for those who were not. A higher proportion of patients in the non-PK-guided group required hospitalization during their lifetime compared with the PK-guided group. This analysis of real-world data suggests that PK-guided dosing for prophylaxis has a beneficial impact on clinical and healthcare resource utilization outcomes in patients with hemophilia A. [Abstract copyright: © 2022 Ferri Grazzi et al.

The impact of bleeding event frequency on health-related quality of life and work productivity outcomes in a European cohort of adults with haemophilia A: insights from the CHESS II study.

From PubMed via Jisc Publications RouterHistory: received 2022-12-12, accepted 2023-04-02Publication status: epublishHaemophilia A carries a substantial healthcare burden, affecting health-related quality of life (HRQoL). The Cost of Haemophilia in Men: a Socioeconomic Survey II (CHESS II), a retrospective real-world study, characterised the burden of haemophilia and its impact on HRQoL and work productivity. The current analysis explored the impact of bleeding events on HRQoL and work productivity in Europe. This analysis focused on data collected from males aged 18 to 64 years with haemophilia A without inhibitors who were receiving replacement factor products or a monoclonal antibody and were not participating in a clinical trial at the time of study recruitment. Descriptive statistics were analysed using scores from EuroQoL's EQ-5D-5L index and EQ-VAS analogue scale and the Work Productivity and Activity Index Specific Health Problem (WPAI:SHP) percentage scores stratified by the number of annual bleeding events (ABs) 0, 1, 2, 3-4, or ≥ 5. Of 918 males with haemophilia A in CHESS II, 318 met inclusion criteria and had data available for HRQoL measures; mean age (SD) was 33.8 (12.1) years and 96% were White. Mean (SD) ABs of 2.7 (2.9) occurred over the preceding 12 months: 20% had 3 or 4 ABs; 17% had ≥ 5 ABs. Mean EQ-5D-5L index scores for patients with 0, 1, 2, 3-4, or ≥ 5 ABs were 0.92, 0.76, 0.76, 0.71, and 0.56, respectively. Mean (SD) EQ-VAS scores were 86.9 (13.6), with 0 ABs versus 69.5 (19.1) for 3 or 4 ABs and 61.2 (17.2) for ≥ 5 ABs. Mean percentage of overall work productivity loss on the WPAI:SHP questionnaire ranged from 9.70 to 0 ABs to 47.65 for ≥ 5 ABs. In this European sample of adult men with haemophilia A, HRQoL and work productivity scores were lower among those reporting more AB events. Bleeding burden appears to affect HRQoL and productivity; however, this cross-sectional analysis limits the ability to draw firm conclusions on causality. [Abstract copyright: © 2023. Institut National de la Santé et de la Recherche Médicale (INSERM).

Anxiety and depression among adults with haemophilia A: Patient and physician reported symptoms from the real-world European CHESS II study.

From PubMed via Jisc Publications RouterHistory: received 2023-11-01, revised 2024-03-01, accepted 2024-03-04Publication status: aheadofprintFunder: SanofiFunder: BioMarin PharmaceuticalFunder: TakedaThe physical pain and disability affecting many people with haemophilia A (PwHA) are known detractors from psychological wellbeing. While psychosocial support is considered a core tenet of the haemophilia comprehensive care structure, the extent to which mental health challenges are detected and monitored by the individuals treating haematologist remains relatively unexplored. To describe prevalence of anxiety and depression in a real-world cohort of adult PwHA and evaluate the congruence in reporting of anxiety or depression (A/D) between PwHA and their treating physicians. Data for PwHA without inhibitors was drawn from the European 'Cost of Haemophilia: A Socioeconomic Survey II' (CHESS II) study. Haematologist-indicated comorbidities of anxiety and depression were unified into a single A/D indicator. The EQ-5D-5L health status measure was used to characterise self-reported A/D, with individuals stratified into two non-mutually exclusive subgroups based on level of A/D reported (Subgroup A: 'some' or above; Subgroup B: 'moderate' or above). Of 381 PwHA with evaluable EQ-5D-5L responses, 54% (n = 206) self-reported at least some A/D (Subgroup A) and 17% (n = 66) reported at least moderate A/D (Subgroup B). Patient-physician congruence in A/D reporting was 53% and 76% for Subgroups A and B, respectively. Descriptive analysis suggested that individuals with physician- and/or self-reported A/D experienced worse clinical outcomes (bleeding events, joint disease, chronic pain). While adverse clinical outcomes appear to correlate with A/D, self-reports of moderate-severe symptoms occasionally lacked formal recognition from treating physicians. Cross-disciplinary surveillance of mental health issues could improve both psychological and clinical outcomes among PwHA. [Abstract copyright: © 2024 John Wiley & Sons Ltd.