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

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

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.