Introduction
The development of an anti‐FVIII inhibitor is the most serious complication of haemophilia A occurring in up to 30% of severe haemophilic patients. The current management of haemophilia ...A with inhibitor uses bypassing agents (BPA) and represents a significant therapeutic burden together with a limited adherence to prophylactic treatment. Emicizumab is the first monoclonal antibody developed in haemophilia A approved for the prevention of bleeding episodes in patients with anti‐FVIII inhibitor.
Aim
The purpose of this study is to evaluate the incremental cost‐effectiveness ratio (ICER) of emicizumab versus BPAs.
Methods
A Markov model was developed over a five‐year time horizon to estimate the comparative costs and benefits of the different therapeutic approaches in this rare disease. Model inputs were clinical, including annual bleeding rate and quality of life, and economical including mainly costs of prophylaxis, bleeds and adverse events.
Results
Emicizumab treatment is dominant, ie lest costly and more effective, in the base‐case analysis saving 234 191 € for a gain of 0.88 QALY. This is confirmed by both the deterministic and probabilistic sensitivity analyses. The main limit of the study remains the absence of long‐term clinical data allowing to relate treatment consumption to clinical benefit, especially in the progression of haemophilic arthropathy.
Conclusion
Our results show that emicizumab is a cost‐effective treatment allowing to consider an easy to implement prophylactic treatment for haemophilia A patients with anti‐FVIII inhibitors.
To describe clinical characteristics, factor consumption, and events of interest in patients with haemophilia A without inhibitors receiving prophylaxis in France, and the clinical impact of ...switching to Elocta® in this population.
This retrospective, observational study using the Système National des Données de Santé database, analysed data from patients with haemophilia A without inhibitors using prophylactic factor VIII (FVIII) replacement therapy during 2016-2019. Clinical characteristics, treatment patterns and switches, factor consumption, and rate of events of interest were determined. In a sub-cohort of patients treated with Elocta®, clinical characteristics, factor consumption, and rate of events of interest before and after switching to Elocta® were compared.
For 545 patients, with mean age (standard deviation SD) 25.4 (17.8) years, Elocta® was the most used treatment. Bleeding events and articular non-bleeding events leading to hospitalization occurred in 15.4% and 13.9% of patients, respectively, and 9.9% of patients had surgeries or procedures related to haemophilic arthropathy. The mean (SD) FVIII product consumption was 344 (93) IU/kg/month for extended half-life treatment, and 331 (98) IU/kg/month for standard half-life products. For the sub-cohort of 146 patients, bleeding events (SD) decreased from 0.32 (2.2) to 0.09 (0.42) events/patient/year (
= 0.227) after switching to Elocta®. There was no statistically significant difference in rates of factor consumption or articular non-bleeding events before and after initiation of Elocta®.
This study provides real-world insights that advance the understanding of treatment patterns and events of interest in patients with haemophilia A on prophylactic regimens in France.
Background
Turoctocog alfa is a recombinant Factor VIII used in patients with hemophilia A. The aim is to assess the real‐life evidence of turoctocog alfa in surgery.
Study Design and Methods
Data ...were extracted from a national database.
Results
Turoctocog alfa was used for 86 surgeries (49 major and 37 minor) in 56 patients. The results are expressed as medians (interquartile range).
Six (10.7%) patients had severe hemophilia A, four (7.1%) moderate, and 46 (82.2%) mild. For patients who underwent major surgeries, basal plasma FVIII coagulant activity (FVIII:C) levels were 15 IU.dL−1 (8–22). Eight (5–14) infusions were given, at a preoperative loading dose of 40.0 (35.0–45.5) IU.kg−1 and a total dose of 253.3 (125.0–507.0) IU.kg−1. In patients who underwent minor surgeries, basal FVIII:C levels were 18 IU.dL−1 (9–31). Two (1–3) infusions were required, at a preoperative loading dose of 34.0 (28.8–38.5) IU.kg−1 and a total dose of 73.7 (37.6–122.1) IU.kg−1. The overall clinical efficacy was judged excellent/good in 77 procedures (89.5%) and fair/poor in nine (10.5%). The fair/poor efficacy concerned seven patients (six mild hemophilia and one severe), for four urological surgeries, two dermatological procedures, one heart surgery, one ear‐nose‐throat procedure, and one dental avulsion in the patient with severe hemophilia. Three out of those seven patients received antiplatelet therapy. No thromboembolic events, anti‐FVIII antibodies, or adverse events were reported.
Discussion
The efficacy and safety of turoctocog alfa were confirmed for the management of surgery in patients with hemophilia A. No adverse events were observed and overall efficacy was good.
IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to ...avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration number NCT02866526; Pre-results.
Summary
Constitutional thrombocytopenias are rare disorders, often difficult to discriminate from acquired thrombocytopenias. More than 80 genes have been described as being at the origin of these ...diseases. Among them, several variants of the glycoprotein Ib platelet subunit alpha (GP1BA) and glycoprotein Ib platelet subunit beta (GP1BB) genes, coding for the GpIb‐IX‐V glycoprotein complex, have been reported in the literature. The study reported here aimed at describing newly identified monoallelic anomalies affecting the GP1BA and GP1BB genes on a clinical, biological and molecular level. In a cohort of nine patients with macrothrombocytopenia, eight heterozygous variants of the GP1BA or GP1BB genes were identified. Five of them had never been described in the heterozygous state. Computer modelling disclosed structure/function relationships of these five variants.
Introduction
In addition to traditional means, topical haemostatics are currently used to avoid haemorrhage during surgery. Although they have been reported to be effective, there is a low level of ...proof of their clinical efficacy, which is at odds with their levels of use. This study used two methods to better understand their in vitro mechanism of action.
Methods
Two clinical biology assays were used to measure the action of topical haemostatics on primary and secondary haemostasis. Calibrated samples of collagen sponges and polypropylene non‐woven gauze were tested. Platelet aggregation was assessed using a multichannel aggregometer. A thrombin generation assay (TGA) was used with a fluorogenic readout. Tissue factor solutions were used to activate coagulation.
Results
In terms of primary haemostasis, collagen sponges stimulated platelet aggregation, in particular between 2 and 5 min after incubation with platelet‐rich plasma and with no dose effect. In regard to coagulation, the kinetics of thrombin generation was enhanced. Polypropylene non‐woven gauze did not exhibit any effect on platelet aggregation, although it did have a weak effect on the kinetics of thrombin generation.
Conclusion
Collagen is well known to exert a haemostatic effect due to its action on platelet aggregation. By contrast, polypropylene non‐woven gauze has not been shown to have any effect on platelet aggregation other than a minor impact on thrombin generation. The results obtained with the devices tested are in agreement with the literature. Platelet aggregation biological assays and TGA measurements appear to be suitable for evaluation of these medical products.
Background
Efmoroctocog alfa, the first recombinant factor VIII fusion protein with extended half‐life (rFVIII‐Fc), has been hypothesized to lower FVIII consumption in patients with severe ...Haemophilia A (pwSHA), without reducing clinical efficacy. What about real life?
Method
MOTHIF‐II was a noninterventional, multicentre, before/after study, via the collection of retrospective data from July 2015 to June 2016 (called T1), and from July 2017 to June 2018 (called T2), in 7 French haemophilia treatment centres. We examined the prescriptions and dispensations of factor VIII and the Annual Bleeding Rate (ABR), in pwSHA without current inhibitors on prophylaxis, before and after the introduction of rFVIII‐Fc. The data gathered from the BERHLINGO research database and from the French Healthcare claims database with a determinist pairing process based on the national unique identification number.
Results
A total of 156 pwSHA were included in the prescription cohort and 83 in the ABR cohort. For switched patients, the mean amounts of prescribed FVIII were significantly higher during T1 compared to T2 (4333 (2052) vs. 3921 (2029) IU/kg/year/patient, p: 0.028); a significant decrease in their ABR was also observed between T1 and T2 (6.3 (6.0) vs. 4.4 (5.4), p: 0.047). These patients had a more severe bleeding profile centred on haemarthrosis.
Conclusion
The results are related to those of the pivotal clinical trials for the reduction in FVIII consumption following the switch to rFVIII‐Fc, with a significant improvement in the haemorrhagic phenotype for pwSHA.
Background
Patients with symptomatic von Willebrand disease (VWD) should be offered long‐term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and ...safety of Voncento®, a plasma‐derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP.
Methods
We included patients from the OPALE study (May 2016 to April 2021), a French multicenter observational study following patients with inherited VWD, who received a Voncento® LTP during the study period.
Results
Among the 130 OPALE‐study patients, 23 patients (12 women) received a LTP and were therefore included. The median (range) age was 16 (1–85) years; 16 patients were type 3, 1 was type 2A, 6 were type 2B. Before inclusion, 19 (83%) were under LTP and 4 (17%) received on‐demand (OD) treatment. The indications for initiating prophylaxis in the overall population were joint bleeding (43%), ear, nose, and throat (ENT) bleeding including epistaxis or oral bleeding (39%), and recurrent muscle hematoma (22%). The medians (ranges) dose of Voncento® per infusion, frequency, and weekly dose were 45 (33–109) IU/kg, 2 infusions per week, and 96 (44–222) IU/kg/week, respectively. The median (range) annualized bleeding rate (ABR) was 0.8, 0.7 (0–3.5), and 0 (0–2.3) for type 2A, 2B, 3 patients, respectively. There was no difference regarding to the dose, frequency of infusion, or in terms of ABR in 9/19 patients who replaced previous concentrates with Voncento®. During the study period, no adverse event was reported.
Conclusion
These results suggest that Voncento® is effective to prevent recurrent bleedings in patients symptomatic VWD.
Introduction
Von Willebrand Disease is a common inherited haemorrhagic disorder due to a deficiency of Von Willebrand Factor (VWF). In case of surgical procedures in patients who are not responsive ...or have contraindications to desmopressin, replacement therapy with VWF concentrates is indicated. Until recently, only plasma‐derived VWF concentrates were available. A new recombinant VWF (rVWF) concentrate that contains no Factor VIII (FVIII) but a high amount of high molecular weight VWF multimers has been available in France since 2018.
Aim
Describe real‐world experience of using rVWF in surgical procedures.
Methods
Sixty‐three surgeries for 55 patients were retrospectively analysed in 7 French haemostasis centres.
Results
During minor surgeries, the median (range) number of infusions was 1 (1–8) with a preoperative loading dose of 35 (19–56) rVWF IU/kg and a total median dose of 37.5 IU (12–288). During major surgeries, the median (range) number of infusions was only 3 (1–14) with a median preoperative loading dose of 36 IU (12–51) rVWF IU/kg, and a total median dose of 108 IU (22–340) rVWF IU/kg. The overall clinical efficacy was qualified as excellent/good in 61 of the procedures (97%), moderate in 1 (1.5%) and poor in 1 (1.5%). There was no accumulation of VWF or FVIII during postoperative monitoring. No thromboembolic events, anti‐VWF antibodies or adverse events were reported.
Conclusion
This French ‘real‐world’ experience shows that a few infusions and low doses of rVWF provided effective prevention of bleeding in major and minor surgeries in inherited VWD, with no clinically significant safety concerns.
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