Barriers to gene therapy, understanding the concerns people with haemophilia have: an exigency sub-study.

BACKGROUND: Gene therapy has the potential to offer people with haemophilia (PwH) a life free from bleeding and the burden posed by current treatment regimens. To date, gene therapy has only been available in clinical trial settings, to PwH without pre-existing or historical factor inhibitors, significant concomitant liver damage or pre-existing neutralising antibodies to the adeno-associated viruses used to deliver the therapy. Thus, most PwH treated at centres not currently involved in gene therapy trials, either as a referral/follow-up centre or as a dosing centre, have been unable to access the therapy. This Exigency sub-study aims to gain a greater understanding of the opinions of PwH in the United Kingdom who have not had access to gene therapy: asking what they understand, what concerns they have, and whether they perceive any barriers preventing their access to gene therapy. RESULTS: Twenty-three PwH were approached; 14 consented, and one withdrew prior to interview. The mean age of the participants was 35.7 years (range 25-74 years). Eleven had haemophilia A and two haemophilia B. Two were treated with standard half-life factor products, five with extended half-life products, five with a FVIII mimetic and one with a clinical trial product. One family member (a participant's partner) was also interviewed. The participants identified four barriers to gene therapy: concerns about the process of gene therapy (Expectations), uncertainty about the results (outcomes), (Access) to treatment, and a lack of understanding about gene therapy (education). CONCLUSIONS: This Exigency study subgroup sees gene therapy as a positive treatment development that promises an improved quality of life. For this participant group, four issues impact their decision to undergo gene therapy. If the promise of gene therapy is to be realised, these barriers need to be acknowledged and addressed by healthcare professionals, patient organisations, and gene therapy providers.

Expectation and loss when gene therapy for haemophilia is not an option: An exigency sub-study.

BACKGROUND: Qualitative studies have explored why people with haemophilia (PwH) might consider or forgo gene therapy, the impact it has had on those who have received it, and what support might be needed throughout the process. No studies have yet examined what withdrawal prior to transfection might mean for PwH and their families. AIMS: To understand the experiences of PwH and their families of withdrawal from gene therapy and to understand what support mechanisms might be required. METHODS: Qualitative interviews were conducted with people with severe haemophilia who consented to take part in a gene therapy study in the UK but either withdrew or were withdrawn before transfection. RESULTS: Nine PwH and a family member were invited to this sub-study. Eight participants were recruited: six PwH (five haemophilia A and one haemophilia B) and two family members. Four participants were excluded from a study after consenting but before transfection, having failed to meet all the inclusion criteria; two withdrew after consenting but before transfection due to concerns including duration of factor expression and the time commitment involved in follow-up. The mean age of participants was 40.5 years (range 25-63 years). Two major themes emerged during the interviews: Expectation and loss. CONCLUSIONS: PwH have many expectations about the difference gene therapy can make to their lives. Studies show that these expectations may not be fully realised. For those who have either withdrawn or been withdrawn from gene therapy, any expectations they had may now be unachievable. The nature of these expectations and the loss expressed by the participants indicate that support needs to be provided to help them and their families manage it.

The experiences of people with haemophilia and their families of gene therapy in a clinical trial setting: regaining control, the Exigency study.

BACKGROUND: Gene therapy has the potential to change the life experience of people with haemophilia and family members. Few studies have sought to explore the impact of gene therapy on both individuals and families. The aim of this study was to capture real-life experiences of gene therapy in People with haemophilia and their families. RESULTS: Sixteen participants with severe haemophilia (11 haemophilia A, five haemophilia B), mean age 41.4 years (range 23-75 years), took part in a single qualitative interview; ten were accompanied by a family member. Mean time since transfection was 3.56 years (range 1-10 years). Participants saw their involvement in gene therapy as a positive experience, freeing them from the personal burden of haemophilia and furthering treatment options for the wider haemophilia community. However, participants reported being unprepared for the side effects of immunosuppression. Some also reported feeling unsupported and having little control over what was happening as their factor levels became the focus of the process. CONCLUSION: The results suggest that strategies need to be put into place to enable PwH fully to understand the process of gene therapy, and thereby make an informed choice as to whether it is a treatment they might wish for themselves. These include early and ongoing education, increased provision of psychosocial support and ongoing qualitative research.

The views of women with bleeding disorders: Results from the Cinderella study.

INTRODUCTION: Despite therapeutic advances in bleeding disorder treatment, over the past 20 years women with bleeding disorders have reported delayed diagnosis, impaired quality of life, dismissive attitudes from health professionals and inappropriate care. AIM: To explore the lived experience of women with a diagnosed bleeding disorder and to improve understanding of their unmet needs. METHODS: Women haemophilia carriers (WHC), women with a diagnosed bleeding disorder (WBD) and women with immune thrombocytopenia (WITP) were invited to complete an online survey. Those who indicated a willingness to be interviewed took part in a focus group or one-to-one interview to further explore their lived experiences. RESULTS: Two hundred and eighty women completed the survey (126 WHC, 96 WBD, 58 WITP) 13 women (seven WHC, three WBD, three WITP) participated in a focus group (11) or individual interview (2). The most frequently reported symptoms were heavy periods (81%) and bruising (81%). Compared to the group as a whole, more WBD took time off work or school due to symptoms, had discussed symptoms with a healthcare professional (HCP), and had seen a nurse or gynaecologist. WHC were least likely to be screened for a bleeding disorder or seen in a specialist setting. Themes discussed included difficulty obtaining a diagnosis, lack of awareness amongst and poor communication from HCPs, stress and anxiety, coping strategies and sources of support. CONCLUSION: Many of the experiences described by women with bleeding disorders 20 years ago remain prevalent. Healthcare provision needs to change to offer them better treatment and support.

The lived experience of a novel disruptive therapy in a group of men and boys with haemophilia A with inhibitors: Emi & Me.

BACKGROUND: People with haemophilia A and inhibitors (PwHi) suffer more orthopaedic complications, bleeding and pain than those without inhibitors. The advent of emicizumab as a prophylactic treatment has led to a reduction in bleed frequency and a significant improvement in overall quality of life. No research to date has examined the nature of this improvement on treated individuals and their families. AIMS: The Emi & Me study aims to capture the real-life experience of using emicizumab for PwHi and their families. METHODS: Participants were recruited through treatment centres, social media and by word of mouth. Each participant and a family member, if available, took part in a semistructured qualitative interview. All interviews were recorded, transcribed verbatim and analysed thematically. All elements of the study were reviewed by local statutory authorities and informed consent was sought from all participants. RESULTS: Fifteen PwHi, mean age 27.2 years (range 8-63 years), most with a family member, participated in a single qualitative interview online (n = 13), by telephone (n = 1) or in person (n = 1). Mean time on emicizumab was 2.26 years (range 1-5 years). Six major themes emerged: bleeds; pain; treatment burden; control; freedom (for both PwHi and family members) and missed potential. Emicizumab prophylaxis has delivered significant improvements in the lives of the participants. Despite these improvements, some participants felt that their pre-existing physical disabilities and the lack of physiotherapy provision had prevented them achieving similar improvements in their functional ability. CONCLUSION: This study shows that in reducing bleeds, pain and treatment burden, emicizumab had given PwHi greater control over their condition, allowing a sense of freedom they had not experienced with factor VIII or bypassing agent prophylaxis. However, for emicizumab to be truly effective, there is a need to ensure the continued availability and accessibility of robust multidisciplinary support services. Without this, it is unlikely that PwHi will realize the life-changing potential offered either by emicizumab or any other novel treatment approach. PATIENT OR PUBLIC CONTRIBUTION: A patient participant (who did not wish to be included as an author of the paper) was involved in the design of the study protocol and interview guide.

An exploration of why men with severe haemophilia might not want gene therapy: The exigency study.

INTRODUCTION: For many people with haemophilia (PwH) gene therapy offers a potential functional cure. However, some have stated that they do not wish to have gene therapy either now or in the future. AIM: This sub-study, part of the larger Exigency programme, assesses the attitudes, views and understanding of those who do not wish to undergo gene therapy. METHODS: Participants were approached via social media and word of mouth referral and invited to participate in a focus group or individual interview to discuss their views. Interviews were recorded, transcribed verbatim and analysed thematically. RESULTS: Ten adult men with severe haemophilia (eight haemophilia A and two haemophilia B), mean age 34.3 years, participated in a 1-h focus group (n = 9) or interview (n = 1). All were on prophylaxis. None reported significant treatment burden, and all had annual bleeding rates of less than five in the previous 12 months. Four major themes emerged: self-identity and its loss, lack of long-term safety and efficacy data, ongoing concerns about past viral infection, and lack of current treatment burden. CONCLUSION: There are many concerns about gene therapy, including eligibility, effectiveness and safety, which may result in individuals declining it as a therapy. These concerns may recede as more data are published. This study reveals a psychological dynamic around self-identity and belonging for PwH. The nature of this dynamic is poorly understood and needs exploration to facilitate support for those making decisions about gene therapy.

Parental perspectives on gene therapy for children with haemophilia: The Exigency study.

INTRODUCTION: Gene therapy is used in life-limiting conditions of childhood. While not a current therapeutic option for children with haemophilia, it may be considered in the future especially for those where access to treatment is limited. AIM: To assess the attitudes and opinions of parents of children with haemophilia about gene therapy as a potential future treatment, by understanding their awareness about gene therapy and what they need to know now and in the future; gauging levels of interest in gene therapy for their children; and exploring perceived current motivations and barriers. METHODS: A mixed methods study with an online questionnaire and in-depth qualitative interviews in focus groups which were analysed using thematic analysis. RESULTS: One hundred and fifty-eight participants commenced the online survey; 63 were fully completed (39%). 60 had heard of gene therapy but few (17/60 [28.3%]) felt they had a good understanding. 38/60 (63.3%) respondents did not know that gene therapy is not available for children. However, most held positive views: 53/60 (88.3%) saying they would consider it for their child. In the interviews, participants (N = 10, all mothers) discussed their awareness and understanding of gene therapy and opinions about it for children, including how this should be communicated to the child and parents. CONCLUSION: A coherent, community-wide strategy for communicating information and news about gene therapy should now be provided for children and families living with haemophilia. This should come primarily from trusted haemophilia nursing teams, who can give tailored, age-appropriate, factual advice.