Personalized Prophylaxis with myPKFiT: A Real-World Cost-Effectiveness Analysis in Haemophilia A Patients.

This study aimed to assess the effectiveness and costs associated with pharmacokinetics-driven (PK) prophylaxis based on the myPKFiT device in patients affected by hemophilia A (HA) in Italy. An observational retrospective study was conducted in three Italian hemophilia centers. All patients with moderate or severe HA, aged ≥ 18 years, capable of having PK estimated using the myPKFiT device, and who had had a clinical visit between 1 November 2019 and 31 March 2022 were included.

Recent Advances in the Treatment of Hemophilia: A Review.

Progress in hemophilia therapy has been remarkable in the first 20 years of the third millennium, but the innovation began with the description the fractionation of plasma in 1946. The first concentrates followed the discovery of FVIII in the cryoprecipitate of frozen plasma and FIX in the supernatant in the early 1960s, which led to the initial attempts at replacement therapy. Unfortunately, the lack of screening methods for viral pathogens resulted in people with hemophilia (PWH) receiving concentrates contaminated by hepatitis A virus, hepatitis C virus, and human immunodeficiency virus, as these concentrates were made from large industrial pools of plasma derived from thousands of donors.

Practical considerations for nonfactor-replacement therapies in the treatment of haemophilia with inhibitors.

New therapeutic agents for haemophilia with inhibitors that are in development or already licensed are expected to provide transformative treatment options. Many of these new therapies are not based on simply replacing the missing factor; new strategies include bispecific antibody technology that mimics factor VIII coagulation function (emicizumab), and inhibition of anticoagulant proteins such as tissue factor pathway inhibitor (eg PF-06741086) and antithrombin (eg fitusiran). These agents are administered subcutaneously and should significantly reduce treatment burden and increase the ability to deliver prophylaxis for patients.

A Practical, One-Clinic Visit Protocol for Pharmacokinetic Profile Generation with the ADVATE myPKFiT Dosing Tool in Severe Hemophilia A Subjects.

Standard pharmacokinetic (PK) assessments are demanding for persons with hemophilia A, requiring a 72-hour washout and 5 to 11 timed blood samples. A no-washout, single-clinic visit, sparse sampling population PK (PPK) protocol is an attractive alternative. Here, we compared PK parameters obtained with a traditional washout, 6-sampling time point PPK protocol with a no-washout, single-clinic visit, reverse 2-sampling time point PPK protocol in persons with severe hemophilia A (SHA) receiving ADVATE.

Joint replacement for the management of haemophilic arthropathy in patients with inhibitors: A long-term experience at a single Haemophilia centre.

Introduction: The association between haemophilia and the so-called 'inhibitors', alloantibodies against the infused factor able to neutralize its clotting activity, is a very rare condition. Those sporadic patients suffer of an even more severe arthropathy and performing primary or revision arthroplasty become truly challenging. Literature about this topic is scarce, consisting in small case series, high rates of complications and mid-term follow-ups.

Pharmacokinetic characteristics of the triple inactivated plasma-derived Kedrion FIX concentrate: data from the KB037 clinical trial.

The pharmacokinetics data of phase I/II clinical trials (EudraCT Number: 2005-006186-14) of the new, triple inactivated plasma-derived Kedrion FIX concentrate was designed according to the recommendations of SSC-ISTH [1,2]: 11 post-infusion FIX/time points samples during the first 72 h. The PK data were also analysed by a modified, less dense, 9 FIX/time points, sample design. The outcomes of the safety and efficacy study and the pharmacokinetics' results have been previously and partially described [3,4].

Non-Compartment and compartmental pharmacokinetics, efficacy, and safety of Kedrion FIX concentrate.

Background: An open-label phase II, multicenter clinical trial was conducted at 11  Haemophilia Centres in  Italy, Romania, and Turkey, to evaluate the pharmacokinetics (PK), efficacy, and safety of high purity, plasma-derived, double virus inactivated and double nano-filtered factor IX (pd-FIX) concentrate (Kedrion FIX), EudraCT Number: 2005-006186-14.

Material And Methods: 16 previously treated patients (PTPs) with severe or moderately severe haemophilia B were enrolled in the study. At enrolment, 14 underwent the first PK assessment (PK I), and the second PK (PK II) assessment was performed after six months of treatment (5 on-demand and nine prophylaxis) at the end of the study.

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.

Pharmacokinetic and safety considerations when switching from standard to extended half-life clotting factor concentrates in hemophilia.

: Plenty of new FVIII/IX concentrates have been developed and entered the market of hemophilia treatment. Others are going to end the long/demanding procedures for approval. Changes of the FVIII molecule (single chain), pegylation of B-domain deleted FVIII, and fusion with Fc succeeded to improve the FVIII half-life, about 4 hours.

Patient satisfaction and acceptability of an on-demand and on-prophylaxis device for factor VIII delivery in patients with hemophilia A.

Background: FuseNGO is a relatively new device consisting of a prefilled dual-chamber syringe (DCS) that was recently introduced for the reconstitution of recombinant factor VIII. Herein, the DCS device was assessed using five questionnaires with the primary aim of evaluating patient perceptions and preferences.

Methods: An observational, non-interventional, longitudinal study on 86 patients with a confirmed diagnosis of hemophilia A was carried out at 21 sites in Italy.

A phase III study comparing secondary long-term prophylaxis versus on-demand treatment with vWF/FVIII concentrates in severe inherited von Willebrand disease.

Background: There is a lack of prospective clinical trials specifically designed to evaluate the benefits of prophylaxis with vWF/FVIII concentrates in patients with inherited von Willebrand disease (vWD). The aim of the study was to compare efficacy of secondary long-term prophylaxis (PRO) with vWF/FVIII in the prevention of bleeding episodes in severe vWD patients to standard of care (on-demand treatment; ODT).

Materials And Methods: In this 12-month, phase III, open-label study (PRO.

Safety of recombinant coagulation factors in treating hemophilia.

Introduction: During the last decade, new FVIII/IX concentrates have been developed for the treatment of patients affected by hemophilia A/B. Significant progress has been achieved regarding their half-life, but the old issue of immunogenicity and new concerns about safety need to be addressed.

Areas Covered: After the implementation of virucidal methods, both plasma-derived and recombinant clotting factor concentrates achieved a very safe profile.

Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients.

The standard therapy for patients with haemophilia is prophylactic treatment with replacement factor VIII (FVIII) or factor IX (FIX). Patients who develop inhibitors against FVIII/FIX face an increased risk of bleeding, and the likelihood of early development of progressive arthropathy, alongside higher treatment-related costs. Bypassing agents can be used to prevent and control bleeding, as well as the recently licensed prophylaxis, emicizumab, but their efficacy is less predictable than that of factor replacement therapy.

Practical aspects of extended half-life products for the treatment of haemophilia.

Haemophilia A and haemophilia B are congenital X-linked bleeding disorders caused by deficiency of coagulation factor VIII (FVIII) and IX (FIX), respectively. The preferred treatment option for patients with haemophilia is replacement therapy. For patients with severe disease, prophylactic replacement of coagulation factor is the treatment of choice; this has been shown to reduce arthropathy significantly, reduce the frequency of bleeds and improve patients' quality of life.

Diagnosis and care of patients with mild haemophilia: practical recommendations for clinical management.

Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU/mL and is characterised by traumatic bleeds.

Simoctocog alfa for the treatment of hemophilia A.

Hemophilia A is the most frequent inherited bleeding disorder and most challenging coagulation disorder. To combat this, a number of new improved rFVIII/IX concentrates have recently been approved. Some of them are derived from protein fusion biotechnology or pegylation to extend their half-life (HL).

Haemophilia B: Where are we now and what does the future hold?

Research has been lacking on the natural history, complications, and treatment of haemophilia B, which is less common than haemophilia A and was recognized as a distinct clinical entity in 1947. Although the two diseases share the same clinical manifestations, they differ in causative mutation, risk of inhibitor development, and patient quality of life. Frequently debated is whether haemophilia B is as clinically severe as haemophilia A, with much of the published data on overall and haemophilia-specific health outcomes suggesting that haemophilia B may have a less severe clinical phenotype.

The History of Clotting Factor Concentrates Pharmacokinetics.

Clotting factor concentrates (CFCs) underwent tremendous modifications during the last forty years. Plasma-derived concentrates made the replacement therapy feasible not only in the hospital but also at patients' home by on-demand or prophylactic regimen. Virucidal methods, implemented soon after hepatitis and AIDS outbreak, and purification by Mabs made the plasma-derived concentrates safer and purer.

Outcome measures for adult and pediatric hemophilia patients with inhibitors.

Recent advancements in almost all aspects of hemophilia treatment have vastly improved patient care and management, and new and emerging treatments hold the promise of further progress. However, there remains a scarcity of data on long-term outcomes in hemophilia, particularly among those patients with inhibitors, for whom no validated outcome assessment tools are currently available. At the 15 Zürich Haemophilia Forum, an expert panel reviewed the most important outcome measures in inhibitor patients and considered the challenges associated with assessing outcomes in this population.

Emerging drugs for the treatment of hemophilia A and B.

Introduction: Replacement therapy with clotting factor concentrates is the most appropriate and effective way to treat bleedings of Hemophilia A&B to prevent chronic arthropathy. Unfortunately, the short half-life (HL) of FVIII/IX concentrates obliges the patients to receive frequent infusions, a big concern for children. The development of inhibitors in about 30-45% of hemophilia A and in 3-5% of hemophilia B patient is the major adverse event of replacement therapy.

Correlation between FIX genotype and pharmacokinetics of Nonacog alpha according to a multicentre Italian study.

Introduction: Pharmacokinetic (PK) studies on recombinant FIX concentrate, Nonacog alpha, were conducted with different sampling time designs which gave rise to not complete and homogenous outcomes. In addition, patient's FIX genotype/PK relationship has never been investigated.

Aim: Investigate how different sampling times may affect PK parameters and try to find a FIX genotype/PK relationship.