Association of factor expression levels with annual bleeding rate in people with haemophilia B

From Wiley via Jisc Publications RouterHistory: received 2022-01-13, rev-recd 2022-07-29, accepted 2022-08-08, pub-electronic 2022-11-04Article version: VoRPublication status: PublishedIntroduction: Gene therapy clinical trials measure steady‐state clotting factor expression levels (FELs) to evaluate the modulation of the bleeding phenotype, aiming to offer consistent protection against breakthrough bleeding events. The link between FELs and bleeding risk in people with haemophilia B (PwHB) is not well understood. Aim: We evaluated the association between FEL and ABR in PwHB. Methods: This cross‐sectional study extended the CHESS burden of illness studies in Europe and the United States. Recruitment of additional adult males with haemophilia B supplemented the existing CHESS sample size of PwHB and FELs. PwHB receiving prophylaxis were excluded, as fluctuating FELs may have confounded the analysis. Demographic and clinical characteristics were reported descriptively. Any recorded baseline FEL was reported by the haemophilia‐treating physicians according to the medical records. Generalised linear models with log link explored the association between changes in FEL and ABR. Results: The study included 407 PwHB and no inhibitors receiving on‐demand treatment. Mean age was 36.7 years; 56% from the EU, 44% from the United States. Mean baseline FEL was 9.95 IU/dl (SD, 10.47); mean ABR was 2.4 bleeds/year (SD, 2.64). After adjusting for covariates, the model showed that for every 1% increase in FEL the average ABR decreased by .08 (p < .001). Predicted number of bleeding events according to FEL showed a significant non‐linear relationship between FEL and ABR (p < .05). Conclusion: This analysis showed a significant relationship between FEL and ABR, where increases in FEL were associated with decreases in ABR among men with HB in Europe and the US

Patient preferences and priorities for haemophilia gene therapy in the US: A discrete choice experiment

From Wiley via Jisc Publications RouterHistory: received 2021-04-29, rev-recd 2021-06-23, accepted 2021-07-15, pub-electronic 2021-07-26Article version: VoRPublication status: PublishedAbstract: Introduction: Gene therapy has shown promise in clinical trials for patients with haemophilia, but patient preference studies have focused on factor replacement treatments. Aim: We conducted a discrete choice experiment (DCE) to investigate the relative importance and differential preferences patients provide for gene therapy attributes. Methods: We surveyed male adults with haemophilia in the United States recruited from patient panels including the National Hemophilia Foundation Community Voices in Research platform using an online survey over 4 months in 2020/21. Participants indicated preferences for gene therapy attributes including dosing frequency/durability, effect on annual bleeding, uncertainty related to side effects, impact on daily activities, impact on mental health, and post‐treatment requirements. The relative importance of each attribute was analysed overall and for subgroups based on haemophilia type and severity. Results: A total of 183 males with haemophilia A (n = 120) or B (n = 63) were included. Half (47%) had severe haemophilia; most (75%) were White. Overall, participants gave effect on bleeding rate the greatest relative importance (31%), followed by dose frequency/durability (26%), uncertainty regarding safety issues (17%), and impact on daily activities (11%). Dose frequency/durability had the greatest importance for those with haemophilia B (35%). Conclusion: People with haemophilia prioritised reduced bleeding and treatment burden; the former was more important in haemophilia A and the latter in haemophilia B, followed by safety and impact on daily life in this DCE of gene therapy attributes. These findings and differences can inform clinical and health policy decisions to improve health equity for people with haemophilia

Attitude toward organ donation: a survey in Pakistan

This study was conducted to get an insight into the knowledge, attitude, and practices of the people of Pakistan regarding organ donation (OD), and to understand the various factors that influence these. Systematic sampling was used to generate a sample size of 357. Data collection was carried out via a questionnaire in the outpatient units of our hospital. All kinds of medical and surgical patients were interviewed. Knowledge of ODs that occur in Pakistan and the rest of the world was found to be 65.5 and 72.8%, respectively. The percentage of those willing to donate their organ/s was 59.9%. Knowledge of OD was significantly associated with education and socioeconomic status. Willingness to donate had a significant association with gender. It also had a moderate association with education and socioeconomic status. Awareness of OD and the knowledge that OD can save lives was also significantly associated with the willingness to donate

Cardiovascular Risk Factor Burden in the United Arab Emirates (UAE): The Africa Middle East (AfME) Cardiovascular Epidemiological (ACE) Study Sub-Analysis

Background: The Africa Middle East (AfME) Cardiovascular Epidemiological (ACE) study demonstrated that cardiovascular risk factors are highly prevalent among relatively young adult outpatients attending general practice clinics across AfME regions. Objective Based on broader AfME estimates from the ACE Study, this sub-analysis evaluated the prevalence of cardiovascular risk factors in the United Arab Emirates (UAE), particularly in rural and urban cohorts attending general practice clinics. Methods Data from the cross-sectional ACE study were used, comprising stable, adult outpatients attending general practice clinics in the UAE. The prevalence of six cardiovascular risk factors was analyzed: hypertension, diabetes, dyslipidemia, obesity, smoking, abdominal obesity. Rural populations were defined as living >50km from urban centers, or lack of transportation. Results In this cohort of 495 patients (aged 45.1 years; 49.8% female) from the UAE, a high prevalence of abdominal obesity (71.5%) and dyslipidemia (74.0%) was found. Nearly half of patients had hypertension (43.0%) and one-third diabetes (32.4%). Nearly all outpatients (92.9%) had ≥1 modifiable risk factor (74.9% had ≥1, 59.7% had ≥3). Observations were similar by gender, and across urban and rural centers. Many outpatients with pre-existing hypertension or dyslipidemia did not meet recognized blood pressure or low-density lipoprotein cholesterol goals. Conclusions Cardiovascular risk factors are prevalent among relatively young adult, clinically stable outpatients attending clinics across the UAE. These findings support targeted screening of outpatients visiting a general practitioner, which may provide opportunity for early discovery and ongoing management of risk factors, including recommending lifestyle changes. The ACE trial is registered under NCT01243138

Association of factor expression levels with annual bleeding rate in people with haemophilia B

From Crossref journal articles via Jisc Publications RouterHistory: epub 2022-11-04, issued 2022-11-04Article version: VoRPublication status: Publishe

Bleeding Data across Baseline FIX Expression Levels in People with Hemophilia B: An Analysis Using the 'Factor Expression Study'

From Crossref journal articles via Jisc Publications RouterHistory: ppub 2021-11-05, issued 2021-11-05Publication status: PublishedAbstract Introduction Complications such as spontaneous and trauma-related bleeding events typically experienced by people with hemophilia B (PWHB) are associated with long-term joint damage and chronic pain, and burdensome treatment with intravenous factor IX administration. Gene therapy, designed to enable the endogenous production of the missing clotting factor, has potential for curative benefit in PWHB (Dolan et al, 2018). Due to its link to risk for bleeding episodes, factor expression level (FEL) is commonly used as an endpoint in hemophilia gene therapy trials. However, little data currently exist linking FEL to bleeding risk in PWHB, most notably within the mild range. As such, the aim of this analysis was to examine the relationship between annual bleed rate (ABR) data across baseline FEL in PWHB. Methods Data from adult non-inhibitor PWHB, across Europe and the United States (US) who received clotting factor on-demand (OD), were drawn from the 'Cost of HaEmophilia in adults: a Socioeconomic Survey' (CHESS) studies. The CHESS studies are retrospective, burden-of-illness studies in people with hemophilia A or B, capturing the economic and humanistic burden associated with living with hemophilia. Additional data were collected to supplement the existing CHESS studies, particularly in people with exogenous FEL in the mild and moderate range. ABR was defined as the physician-reported number of bleed events experienced by the patient in the 12 months to study capture. A generalized linear model (GLM) was used to analyze variation in ABR data across FEL, adjusting for covariates age, body mass index (BMI), and blood-borne viruses. Following this, a multivariable restricted cubic spline (RCS) GLM regression was performed to create, model, and test for the potential non-linear relationship between FEL and ABR. The RCS regression employed 3 knots, located at baseline FEL values of 1, 5, and 10, and controlled once again for age, BMI, and blood-borne viruses. Results A total of 407 adult non-inhibitor PWHB, receiving an OD therapy regimen and with information on ABR, were profiled. The GLM provided adequate fit for the modeling of bleed data; the average marginal effect at the mean was computed from the GLM regression outputs. After controlling for the effects of all other model covariates, the regression analysis showed a significant association between FEL and ABR; for every 1% increase in FEL, the average ABR decreased by 0.08 units (p&amp;lt;0.001). The results of the RCS regression found a significant non-linear relationship between FEL and ABR, ceteris paribus (p&amp;lt;0.001). Conclusions The results of this analysis found baseline FEL to be significantly associated with ABR in PWHB; as baseline FEL increased, ABR reduced. This highlights the clinical importance of new hemophilia gene therapies potentially increasing FEL to that of the mild or non-hemophilic range in terms of reducing patient burden through the better prevention of bleeding events in PWHB. Disclosures Ali: UniQure: Current Employment. Li: UniQure: Current Employment. Konkle: Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. O'Mahony: BioMarin Pharmaceutical Inc.: Consultancy; Freeline: Consultancy; Uniqure: Speakers Bureau. Pipe: Apcintex: Consultancy; ASC Therapeutics: Consultancy; Bayer: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Octapharma: Consultancy; Shire: Consultancy

Association of factor expression levels with annual bleeding rate in people with haemophilia B.

From PubMed via Jisc Publications RouterHistory: received 2022-01-13, revised 2022-07-29, accepted 2022-08-08Publication status: aheadofprintGene therapy clinical trials measure steady-state clotting factor expression levels (FELs) to evaluate the modulation of the bleeding phenotype, aiming to offer consistent protection against breakthrough bleeding events. The link between FELs and bleeding risk in people with haemophilia B (PwHB) is not well understood. We evaluated the association between FEL and ABR in PwHB. This cross-sectional study extended the CHESS burden of illness studies in Europe and the United States. Recruitment of additional adult males with haemophilia B supplemented the existing CHESS sample size of PwHB and FELs. PwHB receiving prophylaxis were excluded, as fluctuating FELs may have confounded the analysis. Demographic and clinical characteristics were reported descriptively. Any recorded baseline FEL was reported by the haemophilia-treating physicians according to the medical records. Generalised linear models with log link explored the association between changes in FEL and ABR. The study included 407 PwHB and no inhibitors receiving on-demand treatment. Mean age was 36.7 years; 56% from the EU, 44% from the United States. Mean baseline FEL was 9.95 IU/dl (SD, 10.47); mean ABR was 2.4 bleeds/year (SD, 2.64). After adjusting for covariates, the model showed that for every 1% increase in FEL the average ABR decreased by .08 (p < .001). Predicted number of bleeding events according to FEL showed a significant non-linear relationship between FEL and ABR (p < .05). This analysis showed a significant relationship between FEL and ABR, where increases in FEL were associated with decreases in ABR among men with HB in Europe and the US. [Abstract copyright: © 2022 HCD Economics. Haemophilia published by John Wiley & Sons Ltd.

Association of factor expression levels with health-related quality of life and direct medical costs for people with haemophilia B.

From PubMed via Jisc Publications RouterPublication status: ppublishGene therapy trials aim to provide a functional cure for patients with haemophilia B (HB), and treatment impact is analyzed by factor IX expression levels (FELs). We investigated the relationship of FELs with health-related quality of life (HRQoL) and costs. This was a retrospective cross-sectional analysis of the European (CHESS I-II) and US (CHESS-US) CHESS population studies. Physicians recruited consecutive patients and extracted information from the medical records; patients completed questionnaires between 2014 and 2015 (CHESS-I), 2018-2019 (CHESS-II) and 2019 (CHESS US). Patients with inhibitors were excluded. HRQoL was assessed using the EQ-5D-5L. Twelve-month haemophilia-related direct medical costs included office visits and hospitalizations based on country-level unit costs. A Tobit model was used to analyze FELs and HRQoL and generalized linear models for direct medical costs. A total of 191 men with HB completed the EQ-5D questionnaire; the mean age was 36.8 years, with a mean FEL of 10.1 IU/dL (median, 4.0). Mean EQ-5D was 0.77 (SD, 0.23). The Tobit model adjusting for age, body mass index and blood-borne viruses showed every 1% increase in FEL was associated with +0.006 points in the mean EQ-5D score (  = .003). Mean haemophilia-related direct medical costs excluding factor replacement therapy were €2,028/year (median, €919) in CHESS I-II (EU,  = 226), and $7,171/year (median,$586) in CHESS US (  = 181). Adjusted EU and US models showed every 1% increase in FEL was associated with a decrease in haemophilia-related direct medical costs of €108/year and $529/year, respectively. Direct medical costs were based on physician extraction of encounters from medical records, potentially underestimating costs of care. The voluntary nature of participation may have introduced selection biases. We observed a significant association of increases in FEL with increased HRQoL and decreased costs in Europe and the United States among men with HB and no inhibitors