Haemophilia Community Research Articles

European principles of care for women and girls with inherited bleeding disorders

Despite increasing awareness of issues faced by women and girls with inherited BDs (WGBD), standards of care are lacking, with disparities in diagnosis and treatment for WGBD across Europe. We aimed to develop practical principles of care (PoC) to promote standardization of care for WGBD within European Haemophilia Treatment and Comprehensive Care Centres (HTC/CCCs). The co-creation process, supported by the European Association for Haemophilia and Allied Disorders, consisted of four multidisciplinary meetings with health care providers (HCPs) experienced in WGBD care, and European Haemophilia Consortium representatives, combined with broad patient and HCP consultations in the European haemophilia community. Relevant medical societies outside Europe were contacted for confirmation. We developed ten PoC for WGBD, stressing the importance and benefits of a centralized, multidisciplinary, comprehensive, family-centred approach to support and manage WGBD during all life stages. These PoC emphasise the right to equitable access and quality of care for all people with BDs, irrespective of gender. Multiple medical societies outside Europe also confirmed their support for endorsement. Ten PoC for WGBD evolved from an iterative process among stakeholders, supported by relevant medical societies worldwide. These PoC can serve as a benchmark for diagnosis and comprehensive multidisciplinary management of WGBD, and improve awareness of their unique challenges. They offer a framework to guide HTC/CCCs in providing equitable care for all WGBD, both in their own services and in other healthcare settings. Implementation of these principles aims to positively impact the health, wellbeing and quality of life for WGBD.

Optimizing language for effective communication of gene therapy concepts with hemophilia patients: a qualitative study

BackgroundFor communities of people living with hemophilia and other genetic conditions, gene therapy could represent a paradigm shift in treatment strategies. As investigational therapeutic modalities such as gene therapy become more widely used and discussed, there is a critical need for all stakeholders to communicate using a lexicon that is intelligible, accurate, consistent, and representative of novel treatments. In doing so, expectations can be more carefully managed and potential risks, benefits, and limitations better understood. In recognition of this need, a first-ever study of gene therapy lexicon was conducted using established methods of market research and linguistic analysis.MethodsNinety-four participants representing hematologists, nurses, caregivers, and people with hemophilia A, in six countries (US, UK, Spain, Germany, France, Italy) took part in a series of in-depth interviews, face-to-face focus groups, an advisory board meeting, and online group interviews to develop, refine, and test verbal, written, and pictorial language concepts through a three-phase iterative process. Sessions were conducted in local languages using detailed discussion guides. Feedback from participants was captured using real-time instant-response dial testing to measure moment-by-moment emotional responses to language stimuli. Semiquantitative analysis of the responses informed selection of preferred language concepts for final testing, and qualitative discussion explored preference rationale. Participants also completed polling and forced rank and choice written exercises.ResultsStudy feedback showed that the hemophilia community has preferences around consistent lexicon to describe hemophilia and its management. Expert linguistic analysis of feedback from the three phases enabled agreement of a consensus lexicon of vocabulary and an optimized summary narrative for talking about gene therapy amongst people affected by hemophilia A. Preferences were largely consistent across audiences and countries, although some country-specific recommendations were made. A representative summary phrase was agreed: “Gene therapy is being studied in clinical trials with the aim to allow the body to produce factor VIII protein on its own”.ConclusionsThe use of preferred language across different stakeholders increases understanding and comfort during discussions of novel and complex therapeutic modalities such as gene therapy. Consistent use of community-informed lexicon minimizes miscommunication and facilitates informed decision-making regarding potential future treatment opportunities.

Evolution of haemophilia integrated care in the era of gene therapy: Treatment centre's readiness in United States and EU.

Evolution of haemophilia integrated care in the era of gene therapy: Treatment centre's readiness in United States and EU.

Safety first: Tracking adverse events associated with new therapies for people with hemophilia

Safety first: Tracking adverse events associated with new therapies for people with hemophilia

Beliefs and Values About Gene Therapy and In-Utero Gene Editing in Patients with Hemophilia and Their Relatives.

Hemophilia is an inherited disease for which current treatment is noncurative. While gene therapy and gene editing are being researched, we do not know how the hemophilia community perceives them. Herein, we explore the beliefs and values regarding these new therapies in patients with hemophilia and their relatives. This qualitative study used phone-based semi-structured interviews on 21 adult English-speaking patients with hemophilia A or B and their parents across the United States during March to July 2019. The study was advertised through different chapters of the Hemophilia Foundation. The interview guide included questions about participants' prior experience with hemophilia, and included two case scenarios about the use of gene therapy and in utero gene editing, after which participants were asked about their opinions, beliefs, and values on each scenario. We used a grounded theory approach and identified the main themes using an inductive process. We interviewed 21 participants-12 patients and 9 mothers. Most of them had or were related to a patient with severe disease. The main themes discussed were related to efficacy, safety and financial concerns and insurance coverage for both gene therapy and in utero gene editing. Patients and their parents had expected outcomes in terms of durability of therapy and impact on emotional health and lifestyle changes in the long term. Gene therapy was more accepted among patients with severe and uncontrolled disease. In-utero gene editing was not completely accepted because of safety and ethical issues. Patients with severe hemophilia perceive gene therapy as a potential cure, while gene editing was more controversial. Patients still have questions that remain to be answered regarding safety and efficacy that should be assessed with long-term follow up studies.

Haemophilia care in Europe: Past progress and future promise

Haemophilia care has experienced unprecedented advances over the past 50years, with the promise of a functional 'cure' being within reach in the not so distant future. This review outlines the challenges the haemophilia community in Europe has faced over the decades since the 1970s and how it has overcome them to steadily advance care. It will also look towards the future and anticipate the hurdles to accessing the next wave of innovation and apply how past experience can help reduce or eliminate these hurdles. The lessons we can learn from the past can inform not simply treatment decisions, but shape the policy, advocacy and access environment needed to make the future promise a reality. The future is bright, but only through active participation across the haemophilia community will we be able to achieve it. We need to work together, to ensure progress will not only be realized by those with haemophilia in Western Europe, but by all those with haemophilia and other inherited bleeding disorder throughout Europe.

Making Knowledge Hereditary: Public–Private Partnership Drives Progress in Rare Disease Community

Background: Hemophilia is a rare and complex inherited bleeding disorder in which people may experience prolonged, painful, and debilitating bleeds due to an inability of their blood to clot properly. Although there has been great progress in the management of the disease over the past 50+ years, many important scientific questions have gone unanswered. Further, despite decades-long interest and desire by medical providers and scientists, the U.S. government and the hemophilia community to conduct comprehensive genetic testing to better understand the disorder, challenges such as cost, access, and privacy concerns served as ongoing obstacles. Focus of the Article: To overcome these challenges and address this unmet need, four community organizations and a health communications and social marketing agency came together in 2011 to create a first-of-its kind public–private partnership (PPP) called My Life, Our Future (MLOF) to provide people with hemophilia information about their disorder while also furthering scientific understanding. Importance to the Social Marketing Field: This article will explain how MLOF utilized social marketing to drive broad community engagement, ultimately genotyping more than one third of the U.S. male hemophilia population through the program and opening the MLOF Research Repository, the largest research repository of its kind. It will also discuss the key learnings gleaned through the establishment and implementation of this program, notably the strength of a PPP in health care.

A qualitative, patient-centered perspective toward plasma products supply chain network design with risk controlling

Motivated by a real issue in Iran blood transfusion organization and hemophilia community, this paper aims to design and plan an integrated plasma and plasma-derived medicines supply chain network to improve efficiency and timely access to high-quality services. This paper contributes to the existing literature by incorporating four factors, namely (1) quality, (2) efficiency, (3) type-differentiated demand, and (4) risk controlling into the model. To better manage the quality of plasma, we categorize fresh frozen plasma into two classes based on plasma freezing time interval. Moreover, since the number of available donors and centers accessibility affects the supply chain performance, the ideal candidate locations of plasma donation centers are evaluated through several pivotal criteria via a data envelopment analysis approach. We propose a mathematical model, based on a tactical-strategic decision in a real case. Furthermore, the robustness manages the inherent uncertainty in input data and controls the risk of probable disruption in the model, simultaneously. We consider a real case study according to hemophilia community issues in Tehran. The outcomes assist the practitioners in managing how plasma products should be manufactured to minimize the shortages and also control the robustness against uncertainty and disruption risks.

Cross-cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids\u2019 Life Assessment Tool (CHO-KLAT) in C\xf4te d\u2019Ivoire (the Ivory Coast)

IntroductionHealth-related quality of life evaluation is recognized as an important outcome in the assessment of boys with haemophilia. In fact, reliable health-related quality of life data are even more critical in developing countries to advocate for government agencies to develop national haemophilia care programmes. However, validated tools are not yet available in sub-Saharan African countries.AimsThe purpose of this study was to complete the cultural adaptation and validation of the Canadian Haemophilia Outcomes-Kids’ Life Assessment Tool version2.0 (CHO-KLAT2.0) in Côte d’Ivoire.MethodsThe process included four steps: a linguistic adaptation, cognitive debriefing interviews with children and their parents, a validity assessment with the Pediatric Quality of Life Inventory (PedsQL) as a comparator, and a test-retest reliability assessment.ResultsThe initial Ivoirian version of the CHO-KLAT2.0 was developed through a linguistic adaptation performed in close collaboration with members of the local medical team and haemophilia community. Cognitive debriefings were completed with five boys and their parents, with the final Ivoirian version of the CHO-KLAT2.0 developed in September 2017. The validation process included 37 boys with haemophilia (mean age: 11.4 years; 34 with severe and three with moderate forms of haemophilia, all treated on demand) and their parents. Among the child-reported population (n = 20), we observed a mean CHO-KLAT2.0 score of 51.3 ± 9.2; there was a moderate correlation between the CHO-KLAT2.0 and PedsQL scores (r = 0.581; p = 0.007) and an inverse correlation of the CHO-KLAT2.0 and PedsQL scores with the global rating of the degree to which the boys were bothered by their haemophilia. The mean parent proxy CHO-KLAT2.0 score (n = 17) was 53.5 ± 9.8. Among the parents, we found no significant correlation between the Ivoirian CHO-KLAT2.0 and PedsQL scores or between the parent-reported scores and the parent global ratings of bother. The test-retest intraclass correlation coefficient was 0.879 (95% CI: 0.673; 0.954) for the child-reported questionnaires and 0.880 (95% CI: 0.694; 0.955) for the proxy-reported questionnaires.ConclusionsA cross-culturally adapted and validated version of the CHO-KLAT2.0 for Côte d’Ivoire is now available that enables baseline values to be obtained and intervention outcomes (namely, prophylaxis) to be measured in Ivoirian boys with haemophilia.

“He's a normal kid now”: an ethnographic study of challenges and possibilities in a new era of haemophilia care

Abstract Background Recent treatment option advances in haemophilia care have contributed to a discourse of ‘normality’ around the condition, in which people with haemophilia (PwH) are increasingly expected to live ‘normal’ lives unburdened by their condition. Aim The aim of this article is to explore notions of ‘normality’ in the experience of haemophilia across generations. This is one of the main themes identified in a large-scale ethnographic study of the everyday life of PwH, a broad qualitative investigation of beliefs and experiences related to condition, treatment, and personal ways of managing the condition. Methods The study used ethnographic research methods. Five haemophilia experts helped frame the research design by contributing historical and disease area context prior to the initiation of field research. PwH were recruited through patient organisations in five European countries (Italy, Germany, Spain, UK and Ireland). During field research, study researchers collected data through 8–12 hours of participant observation, semi-structured interviews, written exercises, facilitated group dialogues, and on-site observations of PwH interactions with friends, family, and health care professionals (HCPs). They also conducted on-site observation at haemophilia treatment centres (HTCs) and HCP interviews. The study employed a multi-tiered grounded theory approach and combined data were analysed using techniques such as inductive and deductive analysis, cross-case analysis, challenges mapping, and clustering exercises. This article explores findings related to the discourse of ‘normality’ and is thus focused on a subset of the data from the study. Results Fifty-one PwH, aged 1.5 to 82 years, were interviewed and followed in their daily lives. Six treatment centres were visited, and 18 HCPs were interviewed. The study found that a discourse of present day ‘normality’, as compared to a difficult past, is ingrained in the haemophilia community. As a result, unlike most older PwH (40+), younger PwH (under 18) are not always taught to acknowledge the severity of their condition or how to sense bleeds (disease-related embodied knowledge), and risk unknowingly doing long-term damage to their bodies. Twenty-seven per cent (n=7/26) of younger PwH (children, teenagers) in the study were observed or described as engaging in high-risk behaviours in the short term indicating a lack understanding of long-term consequences. Conclusions These findings suggest that the discourse of ‘normality’ presents a number of challenges that need to be addressed, namely the potential for younger PwH to be unaware of bleeds and the general underreporting of haemophilia-related complications and limitations. One way forward in realising the full potential of advanced treatment could be to teach young PwH, through evidence-based initiatives, how to develop an embodied sense of their bleeds. Furthermore, if the current state of life with haemophilia is accepted as finally ‘normal’, then progress in further improving care may be stalled. It is important that remaining and new challenges are recognised in order for them to be acted upon.

Benefits of Ehl Factor VIII Replacement Therapy in Hemophilia: Observations on Coverage, Physical Activity and Phisiotherapy

Introduction: Prevention of haemophilic arthropathy and quality of life´s (QoL) improvement are still the main goals in the haemophilia community. Haemophilic arthropathy is the result of clinical and subclinical bleeding during everyday activities and/or traumatic situations. Prophylaxis with extended half-life (EHL) factor replacement therapy is understood as an improvement solution for factor VIII (FVIII) PK properties, as half-life (T1/2) and area under the curve (AUC), however few real world data are yet available. EHL improved pharmacokinetic (PK) properties might directly drive into a reduction of the bleeding risk during physical activity (both therapeutical or leisure) for a longer period of time, allowing an increase in QoL. World Health Organization (WHO) has set recommendations focused on the benefits of moderate and intense physical activity to improve joint health as well as to prevent common pathologies (obesity, diabetes, hypertension, cancer, depression, anxiety) and even the risk of death (since the absence of physical activity is the 4th factor risk worldwide). The aim of this study was to define a safe program of physical activity, sport and physiotherapy along the time according the PK profile of patients treated with the EHL rurioctocog alfa pegol. Materials and methods: PK parameters (infusion frequency, dosage, T½, peak level, trough level at 24, 48 and 72 hours (NV24/NV48 and NV72), and time to reach 5%, 2% and 1% FVIII levels (T5,T2 and T1) were analyzed in patients with hemophilia A after switching from an standard half-life (SHL) FVIII to the EHL (rurioctocg alfa pegol) FVIII replacement therapy. Tailored physical activity and physiotherapy programmes in place during SHL treatment were re-evaluated after switching to the EHL according the new individual PK profile. The Functional Independence Score in Hemophilia (FISH) form was used to measure ambulation. Results: Ten patients with hemophilia A (9 severe and 1 moderate) with a mean age of 34.49 (9.46) were analyzed. All the PK parameters evaluated showed a significant statistical improvement after the switch from an SHL to this FVIII EHL (Figure 1, A.). Specifically, higher T½, peak levels and trough levels were achieved using a lower dosage and infusion frequency (Figure 1, B). After switching to the EHL, FVIII trough levels were higher than 5% until 3.4 days (81.5 hours) (Figure 1, C) post-infusion. This allowed us to establish a physiotherapy program as well as an intense-moderate physical activity program in patients without clinical evidence of bleeding events (Figure 1, D). The potentiation physical program to develop muscle tone for elbows, knees and ankles was authorized until the third day of EHL FVIII post-infusion. However, during SHL treatment, vigorous physical activity was never performed after 24 hours of FVIII post-infusion. No joint bleeding events appeared during everyday physical activities nor during physiotherapy programs aimed to maintain joint trajectory and muscle power. Regarding ambulation (FISH), all patients had hemophilic arthropathy in one joint. The results in the item "Run" were: 3 points for 3 patients (activity non comparable to normal activity), 2 points for 3 patients (requires an orthesis) and 1 point for 4 patients (activity not feasible). Conclusions: EHL FVIII replacement with rurioctocog alfa pegol improved significantly all PK parameters compared to SHL factors. The administration of this EHL allows moderate and vigorous physical activity after more than 72 hours post-infusion, due to higher FVIII coverage along the time. Disclosures Querol: Baxalta US INC.: Research Funding. Pérez-Alenda:Baxalta US INC.: Research Funding. Megias:Baxalta US INC.: Research Funding; Grifols: Research Funding. Carrasco:Baxalta US INC.: Research Funding. Cid:Novo Nordisk: Honoraria; Shire, a Takeda company: Honoraria. Bonanad Boix:Baxalta US INC.: Research Funding.

Higher Incidence of Neutralizing Anti-FVIII Antibodies (Inhibitors) in Black and Hispanic American Hemophilia A Patients Enrolled in the My Life, Our Future Programme

My Life, Our Future (MLOF) Research Repository projects are made possible by the enthusiastic participation of the hemophilia community, which to date has collectively donated >9,000 blood samples, and provided associated relevant clinical data, to a central repository maintained by the American Thrombosis and Hemostasis Network (ATHN). Genotyping to determine the hemophilia-causing mutations was carried out by Bloodworks NW and the University of Washington. Donors also agreed to have their coded whole genome sequence (WGS) data made available to researchers approved by an ATHN-sponsored peer review of applications from scientists to access these data for specific projects. This remarkable collaborative effort between the patient and research communities will now allow us to address outstanding clinically relevant questions through adequately powered statistical analyses. Earlier studies of up to ~400 subjects have indicated that Black American and Hispanic American hemophilia A (HA) patients are likelier than White patients (and possibly other racial/ethnic/geographic cohorts) to develop neutralizing anti-factor VIII (FVIII) antibodies, or "inhibitors". Demographic, clinical and genotyping data for 4677 HA subjects (ATHN dataset version date 3/31/19) were analyzed to compare reported inhibitor incidences in the following cohorts: (1) Black vs. White and (2) White Hispanic vs. White non-Hispanic. The Black cohort included 4% Black Hispanic. Race and ethnicity were self-reported and inhibitor histories, titers, outcomes of immune tolerance induction, etc. were also extracted from the questionnaires. To reduce potential confounding due to different hemophilia severity and different HA-causing mutations, subgroup analyses were carried out for (mild + moderate HA) vs severe HA cohorts and for cohorts consisting of specific mutation types. Specific racial/ethnic groups, and mutation types within these groups, were also compared. Finally, the inhibitor incidences of all races/ethnicities with severe HA due to a large deletion mutation vs. severe HA due to an inversion mutation were compared. This report is a first-pass analysis, using Fisher's Exact and Chi-square tests, to analyze trends in the data. Among severe HA subjects, Blacks were likelier to develop an inhibitor than Whites (OR=1.7, CI=1.2-2.2, p<0.0001). White Hispanic subjects were also at higher risk than White non-Hispanics (OR=1.6, CI=1.3-2.1, p<0.0002). Race-associated inhibitor risks for subgroups with severe HA due to an inversion mutation were similar. Interestingly, there were no significant differences between inhibitor incidences in White Hispanic (large F8 deletion) vs. White Hispanic (F8 inversion), White-non-Hispanic (large F8 deletion) vs. White-non-Hispanic (F8 inversion), or Black (large F8 deletion) vs. Black (F8 inversion). Previous retrospective analyses have indicated large deletions are associated with increased inhibitor risk, and some have hypothesized a protective effect (immunologically) of intron-22 inversion mutations. This question was further examined by analyzing the entire cohort (all races + ethnicities). As in the smaller cohorts, there was no significant difference in inhibitor incidences for 143 subjects with a large F8 deletion mutation compared to 972 subjects with an inversion mutation. Overall, this study confirms an increased inhibitor risk for American Black and Hispanic HA patients compared to White patients. The results also argue against inversion mutations conferring lower inhibitor risk compared to other cross-reactive material-negative (i.e. precluding intact FVIII protein expression) mutations. The My Life, Our Future Research Repository is a collection of samples and data developed through a collaboration of the American Thrombosis Hemostasis Network (ATHN), Bloodworks NW and the National Hemophilia Foundation, with support from Bioverativ and under leadership of the PI, Barbara Konkle, MD. Phenotypic data were provided through the ATHNdataset, under stewardship of the ATHN. The partners acknowledge the dedicated efforts of the HTCs and their patients for contributing to this Research Repository. The content of this abstract is solely the responsibility of the authors and does not represent official views of the U.S. Department of Defense or of the My Life, Our Future program or its partners. Disclosures Pratt: Grifols, Inc: Research Funding; Bloodworks NW: Patents & Royalties: inventor on patents related to FVIII immunogenicity.

Patient Perspectives on Novel Treatments in Haemophilia: A Qualitative Study

Background and ObjectiveNew treatments for haemophilia are under development or entering the market, including extended half-life products, designer drugs and gene therapy, thereby increasing treatment options for haemophilia. It is currently unknown how people with haemophilia decide whether to switch to a new treatment. Therefore, the objective of this study was to explore what factors may play a role when Dutch patients and parents of boys with moderate or severe haemophilia make decisions about whether to switch to a different treatment, and how disease and treatment characteristics may affect these decisions. This may aid clinical teams in tailored information provision and shared decision making.MethodsWe conducted interviews among adults with moderately severe or severe haemophilia and parents of young boys with severe haemophilia. We aimed to include participants from a variety of backgrounds in terms of involvement in the haemophilia community, age, treatment centre and treatments. Participants were recruited through the Netherlands Haemophilia Society and a haemophilia treatment centre. Semi-structured interviews were recorded and transcribed verbatim. Thematic content analysis was used to analyse the data.ResultsTwelve people with haemophilia and two mothers of boys with haemophilia were included. In general, participants reported to be satisfied with their current treatment. However, they considered ease of use of the medication (fewer injections, easier handling, alternative administration) an added value of new treatments. Participants were aware of the high cost of coagulation factor products and some expressed their concern about the Netherlands Haemophilia Society’s long-term willingness to pay for current and novel treatments, especially for increased usage due to high-risk activities. Participants also expressed their concerns about the short- and long-term safety of new treatments and believed the effects of gene therapy were not yet fully understood. Participants expected their treatment team to inform them when a particular new treatment would be suitable for them.ConclusionsWith the number of treatment options set to increase, it is important for healthcare providers to be aware of how patient experiences shape patients’ decisions about new therapies.Electronic supplementary materialThe online version of this article (10.1007/s40271-019-00395-6) contains supplementary material, which is available to authorized users.

Burden of mild haemophilia A: Systematic literature review.

IntroductionAlthough the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date.AimTo assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review.MethodsPrespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (≥13 years of age) with mild HA.ResultsSeventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966‐2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta‐analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF‐36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available.ConclusionQuantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under‐represented and unmet needs may remain unaddressed. As paradigm‐changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality.

Impact of the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET) study and its post hoc analyses on clinical practice in the United States: A survey of Haemophilia and Thrombosis Research Society members.

A recent randomized trial, the Survey of Inhibitors in Plasma-Product Exposed Toddlers (SIPPET), confirmed that exposure to recombinant FVIII (rFVIII) products doubled the risk of inhibitor development compared to plasma-derived FVIII (pdFVIII) in previously untreated (or minimally treated) patients (PUPs) with severe haemophilia A. SIPPET post hoc analyses showed that early exposure to rFVIII was more immunogenic and that rFVIII could harm low-risk PUPs with non-null mutations. Clinical implications of SIPPET findings for the haemophilia community were unclear. Study the impact of the SIPPET study and its post hoc analyses on clinical practice for PUPs with severe haemophilia A in the United States. Members of the North American Hemophilia and Thrombosis Research Society (HTRS) completed two online questionnaires related to SIPPET publications and PUP management (study period: 12/2016-8/2018). Over 50% participated the study. Sixty per cent expressed methodological concerns about the SIPPET study, yet 55% shared the study with new families. During the study period, rFVIII selection fell from 43/61 (70%) to 15/54 (28%) while use of pdFVIII and shared decision-making increased from 5/61 (8%) to 9/54 (17%) and from 4/61 (7%) to 10/54 (19%), respectively. Based on post hoc analyses, 44/54 (82%) would change their clinical practice with 31/44 (70%) using pdFVIII for PUPs. Barriers to translation of SIPPET analyses included study design concerns, non-inclusion of novel therapies, inability to perform genetic testing at diagnosis and risk of plasma-derived infections. Despite the methodological concerns about the SIPPET study, this Grade I evidence appears to have influenced the clinical practice of haemophilia providers in the United States.

The national blueprint for pregnancy/birth longitudinal cohorts to study factor VIII immunogenicity: NHLBI State of the Science (SOS) Workshop on factor VIII inhibitors.

Patients with haemophilia can develop inhibitors to exogenous coagulation factors. Some patients are tolerant to factor, while those who develop inhibitors do so early in life. Genetics and environmental factors are known to contribute to inhibitor risk. However, it is not yet possible to predict inhibitor formation or treatment responsiveness in individuals. We hypothesize that factors in the antenatal/neonatal period inform inhibitor risk development. To consider the design of longitudinal studies beginning in the antenatal/neonatal period and the use of new technologies to better understand haemophilia inhibitors. A working group was formed for the NHLBI State of the Science Workshop: Factor VIII Inhibitors: Generating a National Blueprint for Future Research to solicit input from the US haemophilia community and international collaborators to consider design of pregnancy/birth longitudinal cohorts that leverage -omics, existing phenotypic data, and in silico modelling to study inhibitors. An antenatal/neonatal longitudinal cohort should begin with enrolment of pregnant genetic carriers of haemophilia and span the at-risk period for inhibitor development in the child. Data and samples from the mother, placenta, neonate and young child can be obtained that are amenable to existing assays, genomics and other -omics studies. Data can inform in silico prediction and mathematical models. A longitudinal study beginning before birth offers the unique opportunity to study factors that influence inhibitor development prior to exposure. Advances in -omics and computational biology can study complex phenotypes in this rare disease. This study could be accomplished through interdisciplinary efforts and patient community engagement.

The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab.

IntroductionAs a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non‐factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed.AimThe Future of Immunotolerance Treatment (FIT) group was established to contemplate, determine and recommend the best management options for patients with haemophilia A and inhibitors.Discussion and ConclusionsDespite the considerable success of emicizumab in the management of inhibitor patients, the FIT group still sees the importance of eradicating inhibitors. However, the availability of emicizumab and other non‐factor therapies in the future might impact greatly on how ITI is undertaken. Theoretically, concomitant use of emicizumab and FVIII might allow emicizumab to effectively prevent bleeding with lower dose ITI regimens. This might allow for the greater adoption of low‐dose/low‐frequency FVIII ITI regimens, which may result in a reduced need for central venous access devices while still maintaining a reasonable likelihood of ITI success. The FIT group proposes a new management algorithm for current ITI (without emicizumab) and a hypothetical new approach with the availability of emicizumab. As there are no published data regarding the concomitant use of emicizumab and FVIII for ITI, the FIT Expert group encourages the undertaking of properly conducted prospective studies to explore these approaches further.

Newborn screening for haemophilia: The views of families and adults living with haemophilia in the UK.

IntroductionAs genomic sequencing become more efficient and cost‐effective, the number of conditions identified through newborn screening globally is set to dramatically increase. Haemophilia is a candidate condition; however, very little is known about the attitudes of the haemophilia community towards screening.AimThis study aimed to outline the perspectives of adults with haemophilia and their families towards newborn screening.MethodsA paper and online survey on screening were distributed to every family known to the Haemophilia Society UK. Data collection occurred between January and June 2018. In total, 327 participants completed the survey: 76% were a relative of a person with haemophilia and 24% had haemophilia themselves; 83% were living with haemophilia A and 17% with haemophilia B.ResultsThe vast majority supported newborn screening (77%) and preferred it to other forms of screening (preconception or prenatal). Participants supported newborn screening primarily because they viewed it as a means to facilitate early support and treatment, facilitate informed decisions about future pregnancies and prevent the “diagnostic odyssey.” The 23% who did not support the screen did not associate these particular benefits with newborn screening.ConclusionHaemophilia emerged from this analysis as a condition that the vast majority of participants considered a “liveable” disability and one best suited to newborn screening programmes that could improve support to affected families rather than reduce the birth rate of affected children.

The 1st WFH Gene Therapy Round Table: Understanding the landscape and challenges of gene therapy for haemophilia around the world.

In this first in a series of round table meetings, the 1st World Federation of Hemophilia Gene Therapy Round Table was convened to initiate a global dialogue on the expected challenges and opportunities that a disruptive therapy, such as gene therapy, will bring to the haemophilia community. Perspectives from key stakeholder groups, including healthcare professionals, regulators, payors, people with hemophilia and pharmaceutical industry representatives, were sought in the identification of the key issues we expect to face. Didactic presentations and open discussion covered the clinical development of gene therapy in haemophilia; regulatory perspectives of gene therapy; making informed decisions; accessibility, affordability and pricing of gene therapy; and ethical issues of gene therapy clinical trials. These were followed by small group work. This manuscript outlines the key issues identified and the path forward.

Complementary and alternative therapy (CAM) in haemophilia pain management: a review of published literature

Abstract Pain continues to be a significant issue for people with haemophilia (PWH), whether it is acute pain from a joint bleed, a needle stick when receiving clotting factor treatment, or chronic pain from chronic synovitis and arthritic changes. In the US, there has been controversy and uncertainty regarding the use of oral medications and opioids for the management of chronic pain, including haemophilia pain. Both PWH and their clinicians have started to explore nonpharmacologic options for managing pain, with many PWH trying to limit their use of oral pain medication and using alternative methods. There is little research around the use of complementary and alternative medicine (CAM) for pain management in the haemophilia community. This paper aims to provide a comprehensive literature review of current English language research on the use of therapies that fall into four distinctive domains of CAM in PWH. English language articles were obtained via searches in Medline, Embase and CINAHL using the target search words “haemophilia” or “bleeding disorders” in combination with other search terms relating to CAM. All references were considered regardless of year. Twenty-three CAM articles that included PWH or other bleeding disorders were identified; ten were evidence based while the remainder provided case reports and descriptions of CAM use in PWH. This indicates that there is limited current research in the area of CAM use for pain management in PWH. Evidence of the benefit of CAM is seen in studies of its use to treat pain in other conditions and health-related circumstances. Additional evidenced-based CAM research is needed so that alternative pain management therapies can be utilised in a safe and beneficial manner in PWH.