Quality of life in a large multinational haemophilia B cohort (The B-Natural study) - Unmet needs remain.

Introduction: The B-Natural study is a multicentre, multinational, observational study of haemophilia B (HB) designed to increase understanding of clinical manifestations, treatment and quality of life (QoL).

Aim: To characterise and compare QoL in HB across disease severity groups and individuals with inhibitors to identify gaps in treatment.

Methods: A total of 224 individuals from 107 families were enrolled from a total of 24 centres in North America (n = 16), Europe (n = 7) and Asia (n = 1).

Plasma-derived factor X concentrate compassionate use for hereditary factor X deficiency: Long-term safety and efficacy in a retrospective data-collection study.

Background: Coagadex is a high-purity plasma-derived factor X concentrate (pdFX) developed to treat hereditary factor X deficiency (FXD).

Objective: Evaluate the efficacy and safety of pdFX administered to patients with hereditary FXD.

Methods: This was an open-label, multicenter, retrospective analysis of patients receiving pdFX for compassionate use.

Final results of the PUPs B-LONG study: evaluating safety and efficacy of rFIXFc in previously untreated patients with hemophilia B.

PUPs B-LONG evaluated the safety and efficacy of recombinant factor IX Fc fusion protein (rFIXFc) in previously untreated patients (PUPs) with hemophilia B. In this open-label, phase 3 study, male PUPs (age <18 years) with hemophilia B (≤2 IU/dL of endogenous factor IX [FIX]) were to receive treatment with rFIXFc. Primary end point was occurrence of inhibitor development, with a secondary end point of annualized bleed rate (ABR).

The B-Natural study-The outcome of immune tolerance induction therapy in patients with severe haemophilia B.

Introduction: Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher.

Aim: To evaluate the use and outcome of ITI in patients with HB and inhibitors.

Diagnosis, therapeutic advances, and key recommendations for the management of factor X deficiency.

Factor X deficiency is a rare coagulation disorder that can be hereditary or acquired. The typology and severity of the associated bleeding symptoms are highly heterogeneous, adding to the difficulties of diagnosis and management. Evidence-based guidelines and reviews on factor X deficiency are generally limited to publications covering a range of rare bleeding disorders.

Feasibility, safety and acceptability of select outcome measures in a physiotherapy study protocol for boys with haemophilia.

Background: There is a lack of functional performance measures for children and young people with haemophilia (CYPwH) with associated control data from typically developing boys (TDB). The literature advocates development of a core set of outcome measures for different chronic conditions. As medical treatment improves, CYPwH are experiencing better outcomes; therefore, more challenging measures are required to monitor physical performance.

Validation of a perioperative population factor VIII pharmacokinetic model with a large cohort of pediatric hemophilia a patients.

Aims: Population pharmacokinetic (PK) models are increasingly applied to perform individualized dosing of factor VIII (FVIII) concentrates in haemophilia A patients. To guarantee accurate performance of a population PK model in dose individualization, validation studies are of importance. However, external validation of population PK models requires independent data sets and is, therefore, seldomly performed.

Assessing thrombogenesis and treatment response in congenital thrombotic thrombocytopenic purpura.

Despite clinical remission and normal platelet counts, congenital TTP (cTTP) is associated with non-overt symptoms. Prophylactic ADAMTS13 replacement therapy such as plasma infusion (PI) prevents acute episodes and improves symptomatology. There is no current method to investigate disease severity or monitor the impact of treatment.

Simoctocog Alfa (Nuwiq) in Previously Untreated Patients with Severe Haemophilia A: Final Results of the NuProtect Study.

Introduction:  FVIII inhibitor development is the most serious contemporary treatment complication in haemophilia A, particularly in previously untreated patients (PUPs). No inhibitors developed in clinical trials in previously treated patients treated with simoctocog alfa (Nuwiq), a fourth-generation recombinant FVIII produced in a human cell line.

Methods:  The NuProtect study investigated the immunogenicity of simoctocog alfa in PUPs.

Safety and efficacy of nonacog alfa for the treatment of haemophilia B in children younger than 6 years of age in a routine clinical care setting: the EUREKIX registry study.

Introduction: European regulatory authorities request postmarketing safety and efficacy data for factor IX (FIX) products.

Aim: Collect additional clinical data from routine nonacog alfa use in children aged <6 years with haemophilia B.

Methods: The EUREKIX registry included retrospective and prospective data collection phases.

Product type and the risk of inhibitor development in nonsevere haemophilia A patients: a case-control study.

Inhibitor development is a major complication of treatment with factor VIII concentrates in nonsevere haemophilia A. It has been suggested that plasma-derived factor VIII (FVIII) concentrates elicit fewer inhibitors than recombinant FVIII concentrates, but studies in severe haemophilia A patients have shown conflicting results. We designed a case-control study to investigate the clinical and genetic risk factors for inhibitor development in nonsevere haemophilia A patients.

Inhibitor incidence in an unselected cohort of previously untreated patients with severe haemophilia B: a PedNet study.

The incidence of FIX inhibitors in severe hemophilia B (SHB) is not well defined. Frequencies of 3-5% have been reported but most studies to date were small, including patients with different severities, and without prospective follow-up for inhibitor incidence. Study objective was to investigate inhibitor incidence in patients with SHB followed up to 500 exposure days (ED), the frequency of allergic reactions, and the relationship with genotypes.

A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors.

Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor IX (FIX) and FX to restore the function of missing activated FVIII in hemophilia A. Emicizumab prophylaxis in children with hemophilia A and FVIII inhibitors was investigated in a phase 3 trial (HAVEN 2). Participants, previously receiving episodic/prophylactic bypassing agents (BPAs), were treated with subcutaneous emicizumab: 1.

Perioperative laboratory monitoring in congenital haemophilia patients with inhibitors: a systematic literature review.

: Although the use of clotting factor concentrates is the mainstay of haemophilia care, the development of inhibitors complicates disease management. Perioperative management of patients with inhibitors is therefore a challenge. A systematic literature review was performed to identify literature reporting on the perioperative monitoring and management of haemophilia.

Efficacy and safety of simoctocog alfa (Nuwiq®) in patients with severe hemophilia A: a review of clinical trial data from the GENA program.

Simoctocog alfa (human-cl rhFVIII, Nuwiq®) is a 4th generation recombinant FVIII (rFVIII), without chemical modification or fusion with any other protein/fragment. Nuwiq® is produced in a human embryonic kidney cell line (HEK293F), which ensures human-specific post-translational protein processing. Nuwiq® was evaluated in seven prospective clinical studies in 201 adult and pediatric previously treated patients (PTPs) with severe hemophilia A.

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab.

Introduction: As a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non-factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed.

Aim: The Future of Immunotolerance Treatment (FIT) group was established to contemplate, determine and recommend the best management options for patients with haemophilia A and inhibitors.

Discussion And Conclusions: Despite the considerable success of emicizumab in the management of inhibitor patients, the FIT group still sees the importance of eradicating inhibitors.

Characterization and treatment of congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years.

Genotype analysis and identification of novel mutations in a multicentre cohort of patients with hereditary factor X deficiency.

: The objective was to examine the genotypic and phenotypic characteristics of individuals with hereditary factor X deficiency (FXD), a rare autosomal recessive bleeding disorder caused by mutations in the F10 gene located on chromosome 13q34-ter. To date, 149 F10 mutations have been identified as contributory to FXD. Three open-label phase 3 trials enrolled individuals with mild, moderate, or severe FXD.

Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery.

Essentials Factor IX (FIX) dosing using body weight frequently results in under and overdosing during surgery. We aimed to establish a population pharmacokinetic (PK) model describing the perioperative FIX levels. Population PK parameter values for clearance and V1 were 284 mL h70 kg and 5450 mL70 kg.

Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee.

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment.

Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate.

Background: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years.

Aim: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD.