Cost-Effectiveness of Voncento Prophylaxis Versus On-Demand Treatment in von Willebrand Disease in the United Kingdom.

von Willebrand factor (VWF) concentrates may be required for on-demand treatment (ODT) or long-term prophylaxis (LTP) in von Willebrand disease (VWD). This study assesses the cost-effectiveness of LTP compared with ODT in VWD patients treated with Voncento in the United Kingdom (UK). A Markov structure was developed to estimate quality-adjusted life years (QALYs) and costs of VWD treatment over a lifetime horizon.

Bleed treatment with eptacog beta (rFVIIa) results in a low incidence of rebleeding in adult and adolescent patients with haemophilia A or B with inhibitors.

Introduction: Eptacog beta is a novel human recombinant FVIIa approved for use in the United States, European Union, United Kingdom and Mexico for the treatment and control of bleeding in patients with haemophilia A or B with inhibitors (≥12 years). It is also indicated for perioperative care in the same patient population in Europe and the United Kingdom.

Aim: To assess the incidence of rebleeding and review treatment outcomes in subjects with haemophilia with inhibitors enrolled in the phase 3 PERSEPT 1 clinical trial.

International Society on Thrombosis and Haemostasis Clinical Practice Guideline for Treatment of Congenital Haemophilia-A Critical Appraisal.

Introduction: Evidence-based clinical practice guidelines drive optimal patient care and facilitate access to high-quality treatment. Creating guidelines for rare diseases such as haemophilia, where evidence does not often come from randomized controlled trials but from non-randomized and well-designed observational studies and real-world data, is challenging. The methodology used for assessing available evidence should consider this critical fact.

Efficacy of emicizumab in patients with severe haemophilia A without factor VIII inhibitors in Germany: evaluation of real-life data documented by the smart medication eDiary.

Background: Systematically documented data on real-world use of emicizumab, a bispecific antibody factor (F)VIII mimetic, are still lacking in people with severe haemophilia A (PwSHA). Smart medication, a real-time, online platform, monitors treatment administration and outcomes for people with haemophilia A in Germany.

Objective: To evaluate annualised bleeding rates (ABRs) and annualised joint bleeding rates (AJBRs), using data documented in the smart medication eDiary, for PwSHA receiving emicizumab.

[100 years thrombotic thrombocytopenic purpura (TTP) - lessons learned?].

100 years ago Dr. Eli Moschcowitz described the first case of thrombotic thrombocytopenic purpura. For many decades there were no recognized treatment options, and the mortality rate was extremely high.

A novel gene editing lexicon strategy for the haemophilia community: Research plan for development and preliminary results.

Introduction: Despite the progress in gene editing platforms like CRISPR/Cas9 with the potential to transform the standard of care for haemophilia, the language used to explain and discuss gene editing is not aligned across the haemophilia community. Here, we present the objective and rationale for developing a clear, consistent, and globally aligned gene editing lexicon to address these communication gaps.

Methods: Effectively communicating complex gene editing concepts requires a clear and consistent vocabulary.

The management of liver disease in people with congenital bleeding disorders: guidance from European Association for Haemophilia and Allied Disorders, European Haemophilia Consortium, ISTH, and World Federation of Hemophilia.

People with bleeding disorders (PWBD) have been exposed to the risk of developing chronic viral hepatitis and cirrhosis after replacement therapy. Today, the advent of new pharmacologic strategies for the control of hemostasis and the efficacious antiviral therapies against hepatitis C virus and hepatitis B virus have significantly reduced this risk. However, the definitive success for liver health in this clinical setting is also influenced by other factors, such as the severity of liver disease at the time of hepatitis B virus/hepatitis C virus antiviral therapy and the exposure to highly prevalent factors of chronic liver damage (eg, metabolic dysfunction and/or alcohol) that can cause a residual risk of complications such as hepatocellular carcinoma, portal hypertension, and liver insufficiency.

Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS.

Background: Recombinant porcine factor VIII (rpFVIII; susoctocog alfa) is indicated for the treatment of bleeding events (BEs) in adults with acquired hemophilia A (AHA).

Objectives: To assess the safety, utilization, and effectiveness of rpFVIII in clinical practice.

Design: EU post-authorization safety study (PASS) (NCT03199794) was a multicenter, noninterventional, post-authorization safety study conducted in adults with AHA.

Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany.

Background: Real-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps.

Objectives: To describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period.

Methods: PREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment.

Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A.

Background: Acquired hemophilia A (AHA) is an autoimmune bleeding disorder caused by neutralizing antibodies against coagulation factor VIII. Immunosuppressive therapy (IST) is standard of care to eradicate autoantibody production and protect from further bleeding but carries a risk of severe infection and mortality in frail patients with AHA. Recently, emicizumab has been studied for its potential to reduce the need for early and aggressive IST.

A 360-degree perspective on adeno-associated virus (AAV)-based gene therapy for haemophilia: Insights from the physician, the nurse and the patient.

Background: Adeno-associated virus (AAV)-based gene therapy for haemophilia has advanced substantially in the last 13 years; recently, three products have received approvals from regulatory authorities. Although the impact on quality of life seems promising, some limitations remain, such as the presence of pre-existing anti-AAV neutralising antibodies and the occurrence of hepatotoxicity. This review follows the CSL Behring-sponsored symposium at the 27th Congress of the European Hematology Association (EHA) 2022 that examined the haemophilia gene therapy process from a 360-degree multidisciplinary perspective.

Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A.

Introduction: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation.

Aim: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec.

Which patients should be considered for gene therapy.

Gene therapy for haemophilia, utilizing adeno-associated viral vectors (AAVs) and coagulation factor genes, have demonstrated promising results, leading to recent approvals and introduction of the first gene therapy products into clinical practice. For successful and safe use, there are predefined inclusion and exclusion criteria, and the treatment process and associated risks should be thoroughly understood and long-term safety and efficacy carefully evaluated during follow up. As gene therapy becomes more accessible outside of clinical study centers, continuous evaluation of patient eligibility for subsequent AAV-based treatments becomes essential.

Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies.

Three major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: 1) engineering vectors to increase transgene expression; 2) aligning interests of the health system with costs and challenges for the pharmaceutical industry; and 3) refining patient eligibility criteria and endpoint definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models reflecting the heterogeneity of certain clinical settings (e.

Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial.

Background: Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B treatment, was shown to be superior to treatment with continuous prophylactic factor IX in terms of bleeding protection 18 months after gene therapy in a phase 3 trial. We report post-hoc 24-month efficacy and safety data from this trial to evaluate the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B.

Methods: The phase 3 HOPE-B trial enrolled males aged 18 years or older with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), with a severe bleeding phenotype and who were on stable continuous factor IX prophylaxis.

Feasibility and comparability of different platelet function tests in acute stroke with or without prior antiplatelet therapy.

Background: The clinical course of ischemic and hemorrhagic strokes can be influenced by the coagulation status of individual patients. The prior use of antiplatelet therapy (APT) such as acetylsalicylic acid (ASA) or P2Y12-antagonists has been inconsistently described as possibly increasing the risk of hemorrhagic transformation or expansion. Since clinical studies describing prior use of antiplatelet medication are overwhelmingly lacking specific functional tests, we aimed to implement testing in routine stroke care.

Patient perspective on living with mild hemophilia in Germany: results from a nationwide survey.

Introduction: The disease burden and bleeding risk of patients with mild hemophilia may be underestimated. Their health-related quality of life (QoL) may be negatively impacted by insufficient treatment and bleed-related joint damage connected to a potentially delayed diagnosis.

Aim: This study aims to gain information on the care reality and QoL of patients aged ≥12 years with mild hemophilia in Germany.