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Amy D Shapiro,1 Alejandro Fernandez,2 Jerome Teitel,3 Jaco Botha,2 Kate Khair4 1Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA; 2Takeda Pharmaceutical International AG, Zürich, Switzerland; 3St. Michael’s Hospital, University of Toronto, Toronto, ON, Canada; 4Centre for Outcomes and Experience Research in Children’s Health Illness and Disability (ORCHID), Great Ormond Street Hospital, London, UKCorrespondence: Jaco BothaTakeda Pharmaceutical International AG, Thurgauerstrasse 130, Glattpark-Opfikon, Zürich, 8152, SwitzerlandTel +41 79 961 8561Email jaco.botha@takeda.comIntroduction: Neutralizing antibodies to coagulation factor VIII (FVIII) remain a major complication associated with FVIII replacement therapy.Aim: To assess safety and efficacy of immune tolerance induction (ITI) therapy with ADVATE® (antihemophilic factor [recombinant] [rAHF]) in patients who participated in the Prospective ADVATE Immune Tolerance Induction Registry (PAIR) study.Methods: The PAIR study was an international, multicenter, open-label, prospective, observational study in patients with hemophilia A and inhibitors, prescribed rAHF ITI therapy in clinical practice. The primary endpoint was adverse event (AE) reporting; the secondary endpoints included incidence of central venous access device-related complications and success rates of ITI therapy. Maintenance of immune tolerance was monitored for 12 months post-ITI therapy.Results: Of 44 patients, 36 completed ITI therapy, including 31 completing the 12-month follow-up. Most patients received rAHF 90– 130 IU/kg/day (59.1%) and a mean of 6.0 doses/week; the median duration of rAHF ITI therapy during the PAIR study was 600 days. Overall, 284 AEs were reported; 56 AEs were serious, of which none were considered rAHF-related. Of 228 nonserious AEs, 14 (in six patients) were deemed rAHF-related: increase of FVIII inhibitors titer due to anamnestic response, nausea, catheter site pain, pyrexia, urticaria, upper respiratory tract infection, arthralgia, and hemarthrosis. None were severe or led to ITI discontinuation. Eighteen patients experienced ≥ 1 central venous access device-related complication, and 21 of 36 completers achieved a negative inhibitor titer. The Kaplan–Meier estimate of success for achievement of first negative titer at 18 months of ITI therapy was 68.3% (95% confidence interval 51.8– 83.6%) among completers. Of patients with partial or complete success post-ITI, 87% (20/23) maintained immune tolerance at 12-month follow-up.Conclusion: Data suggest that rAHF ITI therapy in the PAIR study was effective, with no unexpected safety signals reported.Keywords: hemophilia A, immune tolerance, post-marketing product surveillance, therapeutics, adverse effects

Gene therapy presents a potentially transformational approach to haemophilia management. The patient journey for gene therapy is unlike that for other haemophilia treatments, and its one-time, irreversible nature has led to broad agreement that informed shared decision-making is essential. Understanding the educational and support needs of people with haemophilia (PwH) who may consider or undergo gene therapy in the future is key to enabling this. A one-day patient advisory board was conducted with the aim of gaining insights on what education and support would enable PwH to have appropriate conversations with health care practitioners (HCPs) about gene therapy and participate in informed shared decision-making. The participants were 11 age-diverse men with severe haemophilia A or B, including six who had received gene therapy in phase 1-3 clinical trials. Two were members of a national patient organisation or a patient organisation leader. Participants agreed that informed shared decision-making was essential for gene therapy, but most felt the choice to have gene therapy would be limited by healthcare budgets and access arrangements. They identified key education needed by PwH to enable true informed decision-making, best delivered through a collaborative approach by patient organisations and HCPs. Eligibility criteria should be more widely shared within the community as part of general education around gene therapy. Gene therapy should be presented as one of a range of treatment options; understanding its risks, uncertainties and benefits is key to managing expectations and minimising treatment remorse. Awareness of how different factor levels impact bleeding tendency and frequency would be helpful, as success of gene therapy cannot be determined by factor activity alone. Other key educational needs included follow-up commitments, the role and potential side effects of corticosteroids or other immunosuppressants, impact on sense of identity, mental health, family planning, and managing bleeds after gene therapy. Teach-back could help ensure appropriate levels of understanding; psychological support could aid managing expectations. Peer-to-peer learning delivered across a variety of platforms, to share experiences of gene therapy and contextualise more ‘formal’ gene therapy education, was considered invaluable.

Access to treatment and healthcare services for people with haemophilia in the United Kingdom (UK) and Republic of Ireland ranks highly by international standards for contemporary haemophilia management. Collaborate & Address Treatment Challenges in Haemophilia (CATCH) is an annual Sobi™ medical education meeting which brings together multidisciplinary haemophilia treaters throughout the UK and Ireland to discuss all aspects of haemophilia management, including associated challenges and unmet need. This report summarises key issues explored and discussed during CATCH 2023, including ‘raising the bar’ in haemophilia care; haemophilia care for women and girls; changing haemophilia treatment paradigms to consider disease impact as well disease severity; bone health and haemophilia; and shared decision-making.

To explore the experiences, views and beliefs of people with severe haemophilia and healthcare professionals (HCPs) on approaches for pain management, as well as their views on exercise being used as an aspect of management. Taking a qualitative inquiry approach using focus groups and semi-structured interviews, participants included people with severe haemophilia living with chronic pain and haemophilia HCPs. Data were analysed using reflexive thematic analysis. Fourteen men with haemophilia with a median age of 47 (range 23–73) and six haemophilia HCPs agreed to participate. Of the people with haemophilia, 11 attended two focus groups and three were interviewed over telephone. Healthcare professionals were interviewed face-to-face. Two themes were conceptualised from the data: (i) haemophilia management and pain management is discordant (imbalance between good haemophilia care but poor pain management, historical medico-social influences on pain management, the need for trust); (ii) uncertain about exercise but clear on what matters (conflicting views on exercise, the need for proof of safety, personalised care). Options for effective pain management remain limited and what is used is heavily influenced by beliefs and experience. Exercise as a treatment option in pain management is conceptually acceptable for people with haemophilia. Effective pain management requires understanding of individual beliefs and fears, and a personalised approach supported by knowledgeable, trusted clinicians. Musculoskeletal joint pain and its relationship with bleeding in people with haemophilia continues to be a management challenge. Current pain management strategies are of limited effectiveness with little evidence of an approach that reflects the multi-modal pain experience. Whilst exercise and rehabilitation approaches are conceptually possible for people with severe haemophilia, barriers remain regarding perception of overall safety and effectiveness. People with severe haemophilia may consider exercise as part of a pain management strategy if it is individualised, and they are supported to do it by clinicians who understand them and their haemophilia. [ABSTRACT FROM AUTHOR]

To explore the life experiences of pain in people with severe haemophilia and understand how such experiences influence beliefs and sensation of pain in adulthood. A qualitative inquiry approach using focus groups and semi-structured individual interviews was used. Participants included people with severe haemophilia living with chronic pain. Data were analysed using reflexive thematic analysis. Fourteen men with a median age of 47 (range 23–73) agreed to take part. Eleven participated in two focus groups and three were interviewed over telephone. Two themes were conceptualised from the data: (i) haemophilia and pain – an evolving life biography (the personal narrative, historical, social, and medical context, continuous adaptation of activity choices, surveillance of pain and its meaning); (ii) "My normal isn't normal" – identity and self-agency (pain as a feature of life and identify with severe haemophilia, loss of enjoyable activities balanced against staying active, barriers to participation). Pain is a constantly evolving, lifetime feature for many adults with haemophilia and it is viewed as part of their identity with their condition. Healthcare professionals working in haemophilia should try to better understand the influence of an individuals lived experience with their haemophilia on beliefs and behaviours of pain. Severe haemophilia is a rare bleeding disorder that results in musculoskeletal joint disease. Adults with severe haemophilia have experienced multiple episodes of bleeding related musculoskeletal pain since childhood. Pain beliefs and behaviours in adulthood appear to be influenced by a lifetime of painful experiences associated with haemophilia. In order to better support people with haemophilia and chronic pain, healthcare professionals in haemophilia need to better understand how an individuals lived experience of pain helps inform their beliefs about it. [ABSTRACT FROM AUTHOR]

For retention in clinical trials of investigational medical products (CTIMPS), the strategy and tactics to keep enrolled participants from discontinuing participation (dropouts) are important. Haemophilia trials often have extended follow-up and require motivated participants who commit for the duration of the study, which may be underestimated at initiation. Study discontinuation may lead to inconclusive results and prolonged trials. Research nurses (RNs) and study coordinators (SCs) play an important role in clinical trials and are considered the link between principal investigator and study participants. We discuss the importance of the RNs and SCs in retention of participants, the barriers and challenges to retention, and the interventions utilised to support it.

Arch Dis Child 2002;86:297-301 Hermansky--Pudlak syndrome (HPS) is a rare disorder characterised by oculocutaneous albinism, a bleeding tendency, and lipofuscinosis. This retrospective study reviews the clinical history and haematological features [...]