Patient Perspective on Disease Burden and Gene Therapy for Hemophilia A and B: The "Haemvolution for Patients" Italian Survey.

Hemophilia is a rare X-linked congenital bleeding disorder due to a deficiency of factor VIII (hemophilia A [HA]) or factor IX (hemophilia B [HB]). Replacement and nonreplacement treatments are available but have limitations. Gene therapy (GT) provides an effective, long-term, single-dose treatment option, now approaching clinical practice. This study aimed to understand patient perspectives on GT for HA and HB in Italy using a qualitative questionnaire distributed through Italian patient associations, addressing patient views on daily life, treatments, unmet needs, quality of life (QoL), and GT for hemophilia. In total, 141 participants had HA, and 14 had HB (severe 78.6%). Daily life was most affected by pain and/or joint function limitations (57.5% of participants), high infusion frequency (42.5%), management of breakthrough bleeding episodes (40.3%), and anxiety/fear of severe or sudden bleeding (38.8%). Despite current treatments, about half of the participants experienced three or more annual bleeding episodes. Most participants knew of GT (87.2%) and expected improvements in QoL (60.5%), reduced frequency of current treatments (53.5%), and a permanent cure (49.1%); 46.4% were unaware of its once-off dosage and 46.4% were not concerned about the costs they anticipated to be associated with GT. Although several fears were reported, 25.0% of participants were willing to undergo GT with the support of a multidisciplinary team. This survey provided valuable insight into patient perspectives on hemophilia and GT in Italy. Overall, relevant proportions of patients still experience limitations affecting their daily life. Most were positive about GT and anticipated improvements in their clinical outcomes and QoL.

The value-based healthcare approach to haemophilia: Development of outcome measures for the evaluation of care of people with haemophilia.

INTRODUCTION: Considering the advances in haemophilia management and treatment observed in the last decades, a new set of value-based outcome indicators is needed to assess the quality of care and the impact of these medical innovations. AIM: The Value-Based Healthcare in Haemophilia project aimed to define a set of clinical outcome indicators (COIs) and patient-reported outcome indicators (PROIs) to assess quality of care in haemophilia in high-income countries with a value-based approach to inform and guide the decision-making process. METHODS: A Value-based healthcare approach based on the available literature, current guidelines and the involvement of a multidisciplinary group of experts was applied to generate a set of indicators to assess the quality of care of haemophilia. RESULTS: A final list of three COIs and five PROIs was created and validated. The identified COIs focus on two domains: musculoskeletal health and function, and safety. The identified PROIs cover five domains: bleeding frequency, pain, mobility and physical activities, Health-Related Quality of Life and satisfaction. Finally, two composite outcomes, one based on COIs, and one based on PROIs, were proposed as synthetic outcome indicators of quality of care. CONCLUSION: The presented standard set of health outcome indicators provides the basis for harmonised longitudinal and cross-sectional monitoring and comparison. The implementation of this value-based approach would enable a more robust assessment of quality of care in haemophilia, within a framework of continuous treatment improvements with potential added value for patients. Moreover, proposed COIs and PROIs should be reviewed and updated routinely.

Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study.

INTRODUCTION: Current treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AIM: This article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. METHOD: Using the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed literature for AAV-based gene therapy and drafted a list of statements that were circulated to a panel of Italian peers. During two rounds of voting, panel members voted on their agreement with each statement to reach a consensus. RESULTS: The Delphi process yielded 40 statements regarding haemophilia A gene therapy, across five topics: (1) organisational model; (2) multidisciplinary team; (3) patient engagement; (4) laboratory surveillance; and (5) patient follow-up and gene therapy outcomes. The consensus was reached for all 40 statements, with the second round of voting needed for five statements. CONCLUSION: Use of the hub-and-spoke organisational model and multidisciplinary teams are expected to optimise patient selection for gene therapy, as well as the management of dosing and patient follow-up, patient engagement, laboratory surveillance, and patient expectations regarding outcomes. This approach should allow the benefits of AAV-based gene therapy for haemophilia A to be maximised.

Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series.

BAY 81-8973 is an unmodified, full-length third generation recombinant factor VIII (rFVIII) which offers a more favorable pharmacokinetic (PK) profile, compared to its predecessor sucrose-formulated rFVIII (rFVIII-FS). We here report on a retrospective case series of nine patients affected by hemophilia A (HA), with variable disease severity, bleeding phenotype and comorbidities, to underline our clinical practice on prophylaxis with a recently introduced standard hall-life recombinant Factor VIII. The current case series highlights how the current clinical management of hemophilia is able to personalize treatment in several specific conditions like concomitant illnesses with thrombotic risk and allergic reactions.

Health Related Quality of Life and Psychopathological Symptoms in People with Hemophilia, Bloodborne Co-Infections and Comorbidities: An Italian Multicenter Observational Study.

Background: The health-related quality of life (HRQoL) of people with hemophilia (PWH) is an important issue, especially considering people suffering from chronic diseases beyond hemophilia. The principal aim of this study was to investigate the presence and relevance of psychological symptoms, both internalizing and externalizing, lifestyle, and HRQoL in a group of Italian PWH with chronic bloodborne co-infections and comorbidities. Furthermore, the research describes the association between psychological aspects and the impact of disease-related characteristics (type of hemophilia, presence of co-infections, and comorbidities) on them. Methods: Seventy patients (mean age 46.77±11.3), 64 with severe hemophilia A (Factor VIII: C < 1 IU/dL) and 6 with severe hemophilia B (Factor IX <1 IU/dL), were consecutively recruited from seven Hemophilia Centers in Italy of Italian Association of Hemophilia Centers (AICE). In order to assess psychological symptoms, HRQoL, and lifestyle, three psychological questionnaires were administered (the SCL-90-R, SF-36, and PSQ, respectively). Results: A general decline in the quality of life and an increase in the tendency to adopt a lifestyle characterized by hyperactivity emerged. Inverse correlations were found between HRQoL and psychological distress. Although the SCL-90-R did not reveal symptoms above the clinical cut-off, co-infections significantly increased anxiety, depression, somatizations, paranoia, and social withdrawal. Lastly, HRQoL is impaired by co-infections as well as comorbidities. Conclusion: Our preliminary results must be confirmed to deepen the findings between mental health and hemophilia.

Quality of Life in Patients With Cancer Under Prolonged Anticoagulation for High-Risk Deep Vein Thrombosis: a Long-Term Follow-Up.

Current guidelines recommend to prolong anticoagulant treatment in patients with cancer with venous thromboembolism (VTE); only few studies evaluated other parameters than cancer itself for selecting patients at higher risk of recurrent VTE. Long-term management of VTE is thus challenged by several controversies mainly for patients compliance. We here report results of a long-term follow-up in patients with deep vein thrombosis under anticoagulant treatment with low-molecular-weight heparin (LMWH) for residual vein thrombosis (RVT) detected at compression ultrasonography (CUS), 6 months after standard anticoagulant treatment. Patients with RVT were deemed at high risk of recurrences and included in the current observational study. They continued LMWH (reduced at 75% standard dose) for further additional 2 years after enrolment or until death. Patients were followed up every 3 months or earlier, if needed. Among ancillary study end points, there was the assessment of patients' quality of life during daily treatment with subcutaneous injections. Quality of life was determined by the EORTC-C30 questionnaire, administered by a skilled psychologist at enrolment and every 6 months follow-up visits. Overall, 128 patients were evaluated during follow-up. Mean global EORTC-C30 score at enrollment and at 6, 12 and 24 months follow-up were 52.1, 51.4, 50.8 and 50.1, respectively. There were no statistically significant differences between scores at enrolment and at the last available follow-up (P = .1). Long-term treatment with LMWH resulted, effective and safe, it was globally well tolerated and exempt of negative impact on quality of life of the enrolled patients. Reported results support long-term anticoagulant treatment with LMWH in cancer patients at risk of recurrent VTE.