Hervé Chambost

Desmopressin is often administered to correct factor VIII (FVIII) levels in female hemophilia A carriers (HAC). However, the post-desmopressin FVIII pharmacokinetic profiles have been reported only in small case series in this population. Therefore, this study analyzed the post-desmopressin FVIII and von Willebrand factor response in 361 HAC included at 14 French hemophilia treatment centers. A population pharmacokinetic/pharmacodynamic model was developed to analyze the VWF and FVIII levels by taking into account the F8 gene variants (n=143, 39.6%, with null, and n=218, 60.4%, with non-null variants), demographic and laboratory covariates. The prior/after desmopressin mean basal, peak and recovery FVIII:C levels were 0.34 IU.mL-1 (0.08-0.65), 1.13 IU.mL-1 (0.19-2.69), and 2.85 (1.06-7.13), respectively. Peak FVIII:C was ≥0.5 IU.mL-1 in 95.6% (345/361) and ≥0.8IU.mL-1 in 78.7% (284/361) of patients. The covariate analysis showed a poorer desmopressin FVIII response for null than non-null F8 variants: lower mean peak (1.04 vs 1.23 IU.mL-1, p<5.10-5) and lower percentage of patients with normalized FVIII:C (91.6% vs 98.1%, p=0.0068), higher mean clearance (5898.83 vs 2704.06 IU.h-1, p=1.58.10-15), lower mean AUC0-12h (7.73 vs 9.06 IU.mL-1.h, p<5.10-6), and shorter mean time with FVIII:C ≥0.8 IU.mL-1 (1.9 vs 4.1h, p<6.10-6). HAC with body weight <35 kg had lower peak FVIII:C, higher FVIII clearance, lower AUC0-12h, and shorter time with FVIII:C ≥0.8 IU.mL-1 than HAC with body weight 35-70 kg. The ABO blood type did not influence the response to desmopressin. In HAC, the post-desmopressin FVIII response is strongly influenced by the F8 genotype and body weight.

Background: More real-world data are needed to complement existing phase III studies on the efficacy and safety of recombinant factor IX Fc fusion protein (rFIXFc) in people with haemophilia B. Objectives: We report final data from the B-SURE study, evaluating the real-world usage and effectiveness of rFIXFc in France. Methods: Previously treated patients (all ages/severities) received on-demand or prophylactic rFIXFc during B-SURE. Annualised bleeding rate (ABR), injection frequency (IF) and factor consumption (FC) were prospectively evaluated for patients on rFIXFc prophylaxis (primary endpoints). Six months of retrospective factor IX (FIX) data were collected for comparison; patients with ⩾3 months of treatment pre- and post-switch to rFIXFc were analysed. Design: B-SURE was a 24-month, prospective, non-interventional, real-world study across haemophilia treatment centres in France. Results: Ninety-one male patients enrolled across 21 centres (34% n = 63); mean IF and FC were reduced by 38.20 injections/year and 1008 IU/kg/year ( n = 57). In patients with prior FIX on-demand ( n = 15), mean ABR reduced by 84% on rFIXFc prophylaxis ( n = 14), mean IF reduced by 2.13 injections/year and mean FC increased by 381.8 IU/kg/year ( n = 15). Most physicians and patients were satisfied/highly satisfied with rFIXFc prophylaxis. rFIXFc was well tolerated with no new safety concerns. Conclusion: Findings support the safety and effectiveness of rFIXFc, with reduced IF and FC while maintaining/improving bleed protection. Trial registration : NCT03655340.

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.

Summary: This FranceCoag network study assessed 33 patients with congenital factor XIII (FXIII) deficiency presenting FXIII levels versus 3/16 with prophylaxis. In patients exhibiting FXIII levels <10 iu/dl, prophylaxis could be discussed at diagnosis and at pregnancy. Further controlled prospective studies are needed.

Introduction: Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity.Aim: The aim of the analysis was estimating the risk of high‐titre inhibitor associated with the second‐generation full‐length product compared to third‐generation full‐length product and other recombinant FVIII (rFVIII).Methods: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A.Results: A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high‐titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high‐titre inhibitor. The combined analysis indicated a lower risk of high‐titre inhibitor development for the third‐generation rFVIII product compared to the second‐generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third‐generation product compared to the second‐generation product.Conclusion: The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified.

The first Team Haemophilia Education (THE) Meeting was held on 7-8 May 2015 in Amsterdam, The Netherlands. It aimed to promote the optimal care of patients with haemophilia through education of the multidisciplinary treatment team. This was achieved by reviewing the latest developments in haemophilia management, considering how these can be implemented in the clinic to improve patient care and providing a platform for networking and debate for all haemophilia treatment team members. The second THE Meeting was held on 19-20 May in Frankfurt, Germany, and participants included doctors, nurses, physiotherapists, patient representatives and data management staff from 20 different countries. Topics covered the role of the multidisciplinary team in delivering the best haemophilia care, challenges in the management of haemophilia across Europe, available clotting factor treatments, future treatments and the use of genetics in advising carriers of haemophilia. This report is a summary of the key developments in haemophilia care presented by various investigators and healthcare professionals at THE Meeting 2016.