Consensus over the definition of recombinant factor VIII (rFVIII) product classification in haemophilia A is lacking. rFVIII products are often classified as standard half-life (SHL) or extended ...half-life (EHL); despite this, no universally accepted definition currently exists. One proposed definition includes half-life, area under the curve, and technology designed to extend half-life; however, the International Society on Thrombosis and Haemostasis defines activity over time as the most intuitive information for building treatment regimens and the World Federation of Hemophilia describes rFVIII product classification in terms of infusion frequency.
To summarise published data on the clinical and pharmacokinetic criteria used to define rFVIII product classification.
PubMed and EMBASE database searches of English-language articles (2002-2022) were conducted using search strings to identify the relevant population, intervention, and outcomes (e.g., clinical and pharmacokinetic parameters). Articles then underwent title/abstract and full-text screens.
Among 1147 identified articles, 62 were included. Half-life was the most widely reported outcome with no clear trends or product groupings observed. No clear groupings emerged among other outcomes, including infusion frequency, consumption, and efficacy. As activity over time was reported in few articles, further investigation of its relevance to rFVIII product classification is warranted.
The findings of this systematic literature review suggest that parameters other than half-life might be important for the development of a comprehensive and clinically relevant rFVIII product classification definition. There seems to be an opportunity to consider parameters that are clinically meaningful and useful for shared decision-making in haemophilia A treatment.
Prophylaxis treatment is the current standard of care for patients with severe hemophilia. Factor concentrates with improved pharmacokinetics have offered more options for individualizing treatment. ...The treatment focus may be on increased protection, aiming for higher trough factor levels or longer dosing intervals to reduce the burden of hemophilia. Both aspects can have long-term effects on joint health. Products, such as rVIII-SingleChain and rIX-FP have been developed to reduce the treatment burden for patients with hemophilia and optimize prophylactic efficacy. The objective of this report is to provide a summary of the clinical experience of different Hemophilia Treatment Centers in managing the switch to rVIII-SingleChain or rIX-FP in patients with hemophilia.
This report summarizes a selection of patient cases presented at the 3rd Alliance for Coagulation Academy Meeting in October 2020. The cases from the participating centers provide examples of the clinical experience in managing patients' switch to rVIII-SingleChain and rIX-FP, including which types of patients are suitable for switching, and practical steps in managing a switch.
It is important to take into consideration the physical and social fulfillment of the patient when deciding to switch to rVIII-SingleChain or rIX-FP. The physician plays an important role in the motivation of patients as they understand not only the patient's needs but the potential benefits of the new treatment.
The selected patient cases reported here demonstrate that patients may wish to switch factor products for a variety of reasons; therefore, it is critical to understand why patients switch and what they expect from switching.
rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment ...and prevention of bleeding episodes in patients with hemophilia A.
To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis.
This interim analysis includes data, collected between January 2018 - September 2021, from patients treated with rVIII-SingleChain prophylaxis at French Hemophilia Treatment centers. Data on annualized bleeding rates, dosing frequency, and consumption before and after switching to rVIII-SingleChain were recorded. A population PK analysis was also conducted to estimate PK parameters.
Overall, 43 patients switched to prophylaxis with rVIII-SingleChain either from a previous prophylaxis regimen or from on-demand treatment. Following the switch to rVIII-SingleChain, patients maintained excellent bleed control. After switching to rVIII-SingleChain, most patients maintained or reduced their regimen. Interestingly, a majority of patients treated >2 ×/weekly with a standard half-life FVIII reduced both injection frequency and FVIII consumption with rVIII-SingleChain. A PK analysis revealed a lower clearance of rVIII-SingleChain (1.9 vs. 2.1 dL/h) and a longer half-life both in adolescents/adults (
= 28) and pediatric (
= 6) patients (15.5 and 11.9 hours, respectively vs. 14.5 and 10.3 hours) than previously reported.
Patients who switched to rVIII-SingleChain prophylaxis demonstrated excellent bleed control and a reduction in infusion frequency. A population PK analysis revealed improved PK parameters compared with those reported in the clinical trial.
To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Introduction
Health of people with severe haemophilia (PwSH) improves thanks to the advancements in haemophilia care, giving them more opportunities in occupational integration. However, there is ...little literature on the occupational integration of PwSH.
Objectives
The main objective of our study was to assess the occupational integration of PwSH and to compare it with that of the general population. The secondary objective was to study the association between individual characteristics (sociodemographic, clinical and psycho‐behavioural) and occupational integration of PwSH.
Methods
A multicentre, non‐interventional, cross‐sectional study was conducted in 2018–2020 on PwSH, aged over 18 and under 65 years and included in the FranceCoag registry. Measurements included indicators of occupational integration, sociodemographic, clinical and psycho‐behavioural characteristics. The indicators of occupational integration were compared with those of the general population, using indirect standardization. The data of the general population were available from the National Institute of Statistics and Economic Studies (INSEE). Determinants of occupational integration were explored using structural equation modelling.
Results
Of 1262 eligible people, 588 were included. PwSH had a lower employment rate than the general population (standardized ratio, .85; 95% CI, .77–.94). There were more PwSH at tertiary education level than expected (standardized ratio, 1.38; 95% CI, 1.17–1.61). HIV infection, poor physical health and mental health concerns were associated with a higher risk of unemployment in PwSH.
Conclusion
Employment rate of PwSH is lower than that of the general population despite their higher education level. Target interventions focusing on determinants of difficult occupational integration could be helpful for PwSH.
Abstract Introduction The value and challenges of long-term prophylaxis (LTP) in adolescents and young adults need further characterisation. Aim To determine the proportions of adolescents and young ...adults with severe or moderately severe haemophilia in France under LTP and treatment on demand (OD). Methods Patients 15 to 25 years old with haemophilia A or B, factor VIII/IX ≤ 2% and no current inhibitor could be included if they had been under factor VIII/IX treatment at least 12 months and kept a treatment and bleeding diary. Results LTP was administered to 169/212 patients (79.7%) and OD treatment to 40/212 patients (18.9%). The most frequent reasons for initiating LTP were joint bleeding, target joints and frequent bleeds; whereas OD treatment was most often selected on the basis of mild bleeding phenotype or because of constraints on LTP. The mean annual bleed rate (ABR) in the OD group (6.33) was higher than in the LTP group (3.07, p < 0.001). Mean ABR did not differ significantly between age strata (15
–
18, > 18
–
21 and > 21
–
25 years), but was significantly higher for patients with severe haemophilia (4.02) as compared to those with moderate haemophilia (1.97, p = 0.002). No significant difference was observed in mean ABR for joint bleeds between the LTP and OD groups. Physician reported LTP compliance was good or excellent in 97.0% of patients. Conclusion LTP is the predominant factor VIII/IX treatment among adolescents and young adults with severe or moderately severe haemophilia in France. LTP was associated with low ABR and high compliance.
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