INTRODUCTION:Women and girls with bleeding disorders (WGBD) face challenges in accessing timely and specialized care. There is a need for comprehensive data, particularly regarding care and clinical management, to inform advocacy initiatives and policy decisions to standardize and improve access to care. AIM:To conduct a survey of World Federation of Hemophilia (WFH) National Member Organizations (NMOs) on the provision of care and various services for WGBD. METHODS:WFH NMOs completed a questionnaire comprising six themes related to care for WGBD: (1) socioeconomic and cultural challenges, (2) access to healthcare services/programmes/treatments, (3) level of awareness of patients and providers regarding WGBD, (4) availability of programmes and services, (5) challenges in addressing specific needs and (6) challenges in data collection for advocacy, education, and training. RESULTS:Socioeconomic and cultural challenges included women not recognizing/identifying themselves as patients, poverty-related barriers, discrimination and sexism. Obstacles to receiving care encompassed limited awareness and use of diagnostic tools and lack of special clinics. Level of awareness on topics related to WGBD varied greatly across NMOs. Almost half (45%) of NMOs responded they collected data for advocacy purposes; challenges in data collection were mainly due to limited access to reliable and comprehensive data sources. CONCLUSION:The survey identified key challenges in providing and delivering care to WGBD. Strategies and initiatives should focus on raising awareness, expanding access to care, establishing special clinics, and improving outreach, as well as increasing women's representation on committees and boards and increasing education initiatives.

Background:Efanesoctocog alfa is a first-in-class high-sustained factor VIII (FVIII) replacement therapy. In the phase III XTEND-1 (NCT04161495) study, once-weekly efanesoctocog alfa prophylaxis (50 IU/kg) was well-tolerated and achieved high-sustained factor levels in the normal to near-normal range (>40%) for most of the week. Objective:To report outcomes in previously treated participants with severe haemophilia A aged ⩾12 years from an observational study who switched to efanesoctocog alfa prophylaxis during XTEND-1. Design:Paired assessment of participants from an observational study who enrolled in the phase III XTEND-1 study. Methods:Seventy-eight participants switched from marketed standard half-life (SHL) or extended half-life (EHL) FVIII prophylaxis to once-weekly efanesoctocog alfa prophylaxis (50 IU/kg). Endpoints included annualized bleed rates (ABRs), treatment of bleeding episodes, injection frequency and FVIII consumption. Results:Pre-study, 44 (56%) and 34 (44%) participants received SHL FVIII or EHL FVIII prophylaxis, respectively. In the overall population, a significant reduction in ABR from 2.96 to 0.69 (p < 0.0001) was observed following the switch to efanesoctocog alfa prophylaxis as well as reductions in spontaneous, traumatic, joint and spontaneous joint ABRs (p < 0.0001). Significant reductions in mean weekly injection frequency were observed, from 2.8 to 1.0 in the SHL FVIII cohort (p < 0.0001) and from 1.8 to 1.0 in the EHL FVIII cohort (p < 0.0001). Mean annualized factor consumption reduced by 47% in the SHL FVIII cohort and 30% in the EHL FVIII cohort. Conclusion:Collectively, the results of this post hoc analysis demonstrate the benefits of once-weekly efanesoctocog alfa prophylaxis over SHL or EHL FVIII prophylaxis on bleed rates, injection frequency and consumption. Trial registration:Observational study: 242HA201/OBS16221; XTEND-1: NCT04161495 (https://clinicaltrials.gov/study/NCT04161495).

BACKGROUND:The U.S. National Bleeding Disorders Foundation charged seven multidisciplinary working groups (WGs) with developing a National Research Blueprint (NRB) for a novel Bleeding Disorders Research Collaborative (BDRC) firmly rooted in health equity, diversity, and inclusion (HEDI) and centering the knowledge of people living with inheritable bleeding disorders, the Lived Experience Experts (LEEs). RESEARCH DESIGN AND METHODS:The HEDI, LEE, Community Engagement, and Policy WGs met virtually to develop recommendations for BDRC design and operationalization. RESULTS:Engaging, empowering, and elevating guidance and practices to ground BDRC research and operations in HEDI principles are detailed. The full potential of integrating LEE knowledge throughout research conduct and BDRC governance is explored, potential barriers identified, and solutions proposed. Investing in relationships, trust, and transparency are elaborated as keys to meeting community members wherever they are on a research engagement continuum and facilitating desired progression. Expert advocacy and partnerships will be essential to securing policies and funding supporting the BDRC. CONCLUSIONS:The proposed community-inspired BDRC has the potential to catalyze a paradigm shift in U.S. inheritable bleeding disorders research and ultimately advance health equity for all.

Background: Hemophilia carriers (HCs) experience varied bleeding tendencies affecting their quality of life, yet their bleeding phenotype and management remain poorly understood. Since majority of the studies in carriers have focused on women of reproductive age, an unmet need exists to characterize their clinical, laboratory phenotype and treatment patterns across the lifespan. Objectives: The objective of our study was to investigate the age-dependent clinical and laboratory phenotype of hemophilia carriers across the lifespan. We also aimed to study the longitudinal treatment trends in HCs through analysis of the American Thrombosis and Hemostasis Network dataset. Methods: We investigated the age-dependent variation of bleeding phenotype, coagulation factor levels, and trends of utilization of factor concentrates and nonfactor hemostatic therapies (antifibrinolytics, 1-desamino-8-D-arginine vasopressin) in HCs using the American Thrombosis and Hemostasis Network dataset from 2010 to 2020. The study included 3663 HCs (2728 hemophilia A, 935 hemophilia B) divided into 3 age groups: 0 to 12, 13 to 49, and >50 years. Results: Joint bleeding was prevalent across all ages of HCs. While bleeding events were more frequent among HCs within the reproductive-age group, hemophilia B carriers received factor therapy more frequently than hemophilia A carriers (P = .03). Factor (F)VIII activity levels in hemophilia A carriers increased significantly with age (P < .001). Analysis of treatment trends from 2010 to 2020 showed increased utilization of factor concentrates and nonfactor hemostatic therapies among HCs (P < .001 and P = .02, respectively). Conclusion: Our study confirms prior reports of increased bleeding in reproductive-age HCs and identifies lifelong joint bleeding risk. While the rising trend in hemostatic therapy use suggests growing awareness of bleeding tendencies, age-dependent increase in FVIII levels in hemophilia A carriers emphasizes the need for developing tailored management strategies across the lifespan for this population.

BACKGROUND:Despite reports of elevated rates of osteoporosis and fractures in persons with haemophilia (PwH) and von Willebrand disease (PwVWD), routine bone health screening using dual-energy X-ray absorptiometry (DEXA) scans is not consistently implemented for this population across all Haemophilia Treatment Centres (HTCs) in the United States. OBJECTIVES:The primary aim of this study was to examine rates of screening for bone health in PwH and PwVWD with vitamin D levels and DEXA scans. METHODS:We conducted a survey of all federally funded HTCs nationwide from June 2023 to August 2023. Nine multiple-choice questions were developed to explore the roles of HTC providers and their current practices for bone health assessment. RESULTS:The survey achieved a response rate of 44.8% (66 out of 147 HTCs). Among the responding centres, 21 HTCs (31.8%) reported routinely screening for vitamin D deficiency during annual comprehensive visits, while 13.6% (n = 9) performed regular bone health screenings using DEXA scans. Of these nine centres, three were adult HTCs and six were lifespan HTCs. DEXA scans were ordered either by physicians at the HTC (n = 5, 55.5%) or patients were referred to primary care providers, endocrinologists, or other specialists (n = 4, 44.4%). The top three indications for DEXA scans among the responding HTCs included HIV (n = 7, 77.7%), low physical activity or immobility (n = 6, 66.7%), fractures after a minor fall or injury in patients under 50 years of age (n = 5, 55.5%) and vitamin D deficiency (n = 5, 55.5%). These findings underscore the need for specific standardized screening guidelines to optimize bone health screening in PwH and PwVWD.

Background Joint bleeding is the primary determinant of end-stage arthropathy in hemophilia; joint bleeding has greatly decreased with the use of prophylaxis and introduction of highly effective therapies. Aims This study aimed to determine current risk factors for joint bleeding in persons with severe hemophilia A or B. Methods The study analyzed demographic, treatment and bleeding outcome data from Community Counts, a United States (US) National Surveillance project. Data were collected at annual visits between 2013 and 2022. Eligibility included factor VIII or IX <1%, no inhibitor, age 2-44 years, and on continuous prophylaxis. Annual joint bleeding rate (AJBR) differences across demographic and clinical subgroups were compared via rate ratios (RR) and 95% confidence intervals (CI), and with multivariate methods accounting for multiple measurements over time. Results The analysis included 2527 males with hemophilia, 7211 observation years and 10,046 joint bleeds. Lower AJBR in Hem A was most strongly associated with use of emicizumab. For both hemophilia A and B, patient-associated factors, younger age, fewer missed doses, and full employment, were all independently associated with lower AJBR, as was treatment in the Northeast of the US. Conclusions The findings of this comprehensive analysis of a large, diverse sample drawn from hemophilia treatment centers across the United States, underscore the important contributions of patient, community, and treatment factors on joint outcomes in severe hemophilia. Use of emicizumab and few missed doses independently predicted low AJBR highlighting the interplay of access and adherence to care.

What is this summary about? This is a plain language summary of a clinical research study called XTEND-1. The study looked into how safe and effective a medicine called efanesoctocog alfa is for people with severe hemophilia A. Hemophilia A is a genetic condition in which the body does not produce enough or makes dysfunctional clotting factor VIII (eight) – a protein that is essential for blood clotting. People with hemophilia A are prone to dangerous bleeding, particularly internally and into their joints and muscles. How was the research done? The XTEND-1 study compared two ways of using the medication to treat bleeding episodes: (1) injecting it once a week for 12 months as a prophylaxis (regular preventative) treatment, or (2) injecting it as needed for 6 months, followed by weekly prophylaxis treatment for a further 6 months. What did the research find out? People who had prophylaxis treatment with efanesoctocog alfa injections for one year saw a significant reduction in the amount of bleeding they experienced compared to their pre-study prophylaxis treatment. The effects of the treatment also lasted longer, with higher factor VIII levels for longer, than previous prophylaxis treatment and less frequent injections were needed. There was a significant reduction in the amount of bleeding in people taking once-weekly prophylaxis treatment compared to ‘as needed’ treatment.

Hemophilia B (HB) is a rare, hereditary disease caused by a defect in the gene encoding factor IX (FIX) and leads to varying degrees of coagulation deficiency. The prevailing treatment for people with HB (PWHB) is FIX replacement product. The advent of recombinant coagulation products ushered in a new era of safety, efficacy, and improved availability compared with plasma-derived products. For people with severe HB, lifelong prophylaxis with a FIX replacement product is standard of care. Development of extended half-life FIX replacement products has allowed for advancements in the care of these PWHB. Nonetheless, lifelong need for periodic dosing and complex surveillance protocols pose substantive challenges in terms of access, adherence, and healthcare resource utilization. Further, some PWHB on prophylactic regimens continue to experience breakthrough bleeds and joint damage, and subpopulations of PWHB, including women, those with mild-to-moderate HB, and those with inhibitors to FIX, experience additional unique difficulties. This review summarizes the current challenges faced by PWHB, including the unique subpopulations; identifying the need for improved awareness, personalized care strategies, and new therapeutic options for severe HB, which may provide future solutions for some of the remaining unmet needs of PWHB.

A number of barriers in care exist for women/girls with bleeding disorders. Little progress has been made to overcome them, particularly regarding levels of awareness of healthcare professionals (HCPs) and women/girls. To evaluate awareness and perception of heavy menstrual bleeding (HMB) and bleeding disorders among HCPs and women/girls. A three-part qualitative study was conducted, including HCPs and women/girls from over seven countries. Part 1 included eleven 60-min interviews with experts discussing HMB diagnostic barriers, which were further assessed in surveys among 6099 women/girls, 353 general practitioners (GPs), and 426 obstetricians and gynaecologists (OB/GYNs) during Part 2. Part 3 included three 1.5–2-h workshops with 20 clinicians and patient representatives covering HMB knowledge, criteria defining HMB and HCP resourcing for diagnosis. Many HCPs do not conduct certain investigations for women/girls presenting with HMB, and 22% of GPs lack confidence in the management of HMB. Only 8% of GPs use screening tools to evaluate menstrual blood loss, and 13% of GPs and 15% of OB/GYNs assess underlying bleeding disorders. Seventy-six percent of menstruating women/girls believed they could recognise HMB symptoms ‘well’. However, 23% of these women/girls would not seek medical advice for abnormal/prolonged menstruation disrupting their lives. Disruptions were reported in 34% of women/girls from the general population and 61% of women with at-risk symptoms of HMB. Many women/girls and HCPs have limited awareness of important HMB indicators. There is a need for standardized clinical criteria to promote efficient diagnoses and management.

Infants and toddlers (ITs) with hemophilia have unique bleeding features. Factor prophylaxis has been shown to decrease the risk of intracranial hemorrhage (ICH), which supports recommendations to begin at a young age. Clinical and demographic characteristics were analyzed for 883 ITs <= 2 years old with hemophilia A and B, seen at US Hemophilia Treatment Centers and enrolled in the Community Counts Registry, a surveillance program of the Centers for Disease Control and Prevention. ICH in the first 2 years of life was seen in 68 of 883 (7.7%) ITs, of whom 8 of 68 (11.8%) were on continuous prophylaxis at the time of ICH. ITs in this study usually started prophylaxis within the first year of life (mean, 10.3 months), with earlier ages of prophylaxis initiation in later birth cohorts in ITs with hemophilia A. Compared with those without a family history (FH) of hemophilia, known positive FH of hemophilia was associated with earlier age of diagnosis ( P <= .0001) and decreased rates of vaginal delivery ( P = .0006). The use of factor VIII mimetics and extended half-life clotting factor prophylaxis increased with later birth cohorts for ITs with hemophilia A and B. The study highlights that ICH rates in ITs with hemophilia remains substantial and underscores the need for further research to identify modi fiable risk factors to prevent ICH by earlier diagnosis and initiating prophylaxis early, even within the first month of life.

Abstract Inhibitor development is a major therapeutic complication for people with hemophilia. The phase 3 PUPs A-LONG study evaluated the safety and efficacy of efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, herein referred to as rFVIIIFc) in previously untreated patients (PUPs) with severe hemophilia A. Male PUPs <6 years old were enrolled and received rFVIIIFc; inhibitor development was the primary end point. Post hoc analyses, including patient treatment regimen patterns and timing of inhibitor development, descriptive and Kaplan-Meier analyses of time to first inhibitor-positive test by treatment regimen and by titer, and consumption, were performed to describe patients who developed inhibitors during PUPs A-LONG. We investigated patient characteristics (eg, demographics and genotype) and nongenetic risk factors (eg, intense factor exposure and central venous access device [CVAD] placement) that may predict inhibitor development and characteristics of inhibitor development (low-titer vs high-titer inhibitor). Baseline characteristics were similarly distributed for age, race, and ethnicity across both patients who were inhibitor-positive and those who were inhibitor-negative (all P > .05). High-risk F8 variants were associated with development of high-titer inhibitors (P = .028). High-titer inhibitor development was often preceded by the presence of a low-titer inhibitor. Patients whose low-titer inhibitor progressed to a high-titer inhibitor received a higher mean dose per infusion (98.4 IU/kg, n = 5) compared with those whose low-titer inhibitor resolved spontaneously (59.2 IU/kg, n = 7; P = .033) or persisted (45.0 IU/kg, n = 5; P = .047). There was no association between CVAD placement surgery and inhibitor development. Post hoc analyses suggest that F8 genotype and dose of factor are as important as inhibitor risk factors and require further investigation. This study was registered at ClinicalTrials.gov as #NCT02234323.

INTRODUCTION:A number of barriers in care exist for women/girls with bleeding disorders. Little progress has been made to overcome them, particularly regarding levels of awareness of healthcare professionals (HCPs) and women/girls. AIM:To evaluate awareness and perception of heavy menstrual bleeding (HMB) and bleeding disorders among HCPs and women/girls. METHODS:A three-part qualitative study was conducted, including HCPs and women/girls from over seven countries. Part 1 included eleven 60-min interviews with experts discussing HMB diagnostic barriers, which were further assessed in surveys among 6099 women/girls, 353 general practitioners (GPs), and 426 obstetricians and gynaecologists (OB/GYNs) during Part 2. Part 3 included three 1.5-2-h workshops with 20 clinicians and patient representatives covering HMB knowledge, criteria defining HMB and HCP resourcing for diagnosis. RESULTS:Many HCPs do not conduct certain investigations for women/girls presenting with HMB, and 22% of GPs lack confidence in the management of HMB. Only 8% of GPs use screening tools to evaluate menstrual blood loss, and 13% of GPs and 15% of OB/GYNs assess underlying bleeding disorders. Seventy-six percent of menstruating women/girls believed they could recognise HMB symptoms 'well'. However, 23% of these women/girls would not seek medical advice for abnormal/prolonged menstruation disrupting their lives. Disruptions were reported in 34% of women/girls from the general population and 61% of women with at-risk symptoms of HMB. CONCLUSION:Many women/girls and HCPs have limited awareness of important HMB indicators. There is a need for standardized clinical criteria to promote efficient diagnoses and management.

Background Recurrent joint bleeding due to hemophilia often leads to the development of chronic joint disease resulting in chronic pain, decreased joint function and a significant decline in quality of life. Invasive orthopedic interventions (IOI) such as arthroplasty and arthrodesis for end stage joint disease have historically been pursued to decrease pain and improve joint function especially in patients with severe hemophilia and joint disease. Using data collected on patients receiving care in a large network of hemophilia treatment centers in the United States (USHTCN), Tobase et al have previously reported a 5.6% decline in all IOI in patients with hemophilia during the period 2000-2010 (1). Aims The primary objective of the current analysis was to extend those findings using similar data collected during the period 2015-2021 with a focus on IOI indicative of end stage joint disease such as arthrodesis and arthroplasty. Data on IOI were collected annually during the period 2015-2021 from patients who participated in the Community Counts (CC) surveillance project at the 147 member USHTCN using standardized data collection tools. The proportion of patients having IOI in each year was calculated by dividing the total number of patients who reported an IOI by the total number of patients who had a CC visit in that year. Trends in proportions were plotted over time and assessed for statistical significance using the Cochran-Armitage trend test. Results In total, 8,378 CC patients with a diagnosis of hemophilia A or B, over the age of 2 years who completed a subsequent CC visit within last 12 months of last surveillance visit during the years 2015-2021 were included in this study. Enrollees reported a total of 28 arthrodesis and 168 arthroplasty procedures during a total of 21,082 clinic visits over the entire study period. We found that arthroplasty represented 42.6 %, 68.8%, 17.9%, 26.3%, and 7.4% of all procedures reported in the knee, hip, ankle, shoulder, and elbow, respectively (Figure 1). The rate of IOI during the study timeframe remained very low, with only 2.4% of all participants reporting an IOI. During 2015-2021 there was a statistically significant decline in IOI among all patients >=60 years of age (0.59% in 2015 vs. 0.27% in 2021) (p=0.0325) (Figure 2). Similarly, patients with severe hemophilia regardless of age experienced a significant decline in invasive procedures during the study period (1.69% in 2015 vs. 0.88% in 2021) (p=0.021). Conclusions The rates of IOI reported during the years 2015-2021 remained very low (~2.4%). This suggests less joint morbidity and a continued decline in the rates of end stage joint disease during the study period, likely due, at least in part, to improved therapy and early adoption of preventative factor replacement protocols. References 1. Tobase P, Lane H, Siddiqi AEA, et. al. Declining trends in invasive orthopedic interventions for people with hemophilia enrolled in the Universal Data Collection program (2000-2010). Haemophilia, 2016;22(4): 604-614.

Background: One of the most devastating complications of Hemophilia A or B (HemA, HemB) is end-stage joint damage characterized by chronic pain and functional disability. Joint bleeding is the best predictor of joint damage in hemophilia. A wide range of new therapeutics from extended half-life factor (EHL) concentrates to non-factor therapies such as factor VIII mimetics, hemostatic rebalancers and gene therapy have been recently approved or are in late-stage clinical trials that hold the promise of decreased joint disease in severe hemophilia. Specific Aim: Given the progressive improvements in the therapeutic armamentarium of hemophilia care, this study aimed to determine current predictors of joint bleeding in individuals with severe hemophilia on continuous prophylaxis in the context of a national surveillance project. Methods: Eligible participants were males with severe HemA or HemB, aged 2 to 44 years, on continuous prophylaxis therapy and participating in Community Counts (CC) during the period December 2013 to November 30, 2022. CC is a bleeding disorders surveillance project funded by the Centers for Disease Control and Prevention and administered through the American Thrombosis and Hemostasis Network in 141 federally funded Hemophilia Treatment Centers across the United States. CC collects data on sociodemographics, bleeding episodes, treatment products, and health outcomes during patients' annual comprehensive care visits. Data were analyzed using annualized joint bleeding rates (AJBR), calculated using the number and location of all joint bleeds occurring in 10 joints (shoulders, elbows, hips, knees, ankles) during the year since the last surveillance visit based on infusion logs and/or other patient records. Age and other demographic subgroups were compared via rate ratios (RR) and 95% confidence intervals (CI). Methods accounting for multiple measurements from the same individuals over time were used for multivariate analyses. AJBR differences according to demographic and clinical variables were assessed via p values comparing Beta coefficients from these models. Results: The HemA cohort included 2505 persons, 8542 observations years and 13,224 joint bleeds for an overall AJBR of 1.55. The HemB cohort included 439 persons, 1488 observation years and 1326 joint bleeds for an overall AJBR of 0.89. Joint bleeding increased with age. In comparison to those ages 2-9 years, RRs were significantly increased for ages 10-19 and 20-44 for both HemA (1.23 [CI 1.1-1.3]) and 3.17 [CI 3-3.4], respectively), and HemB (2.2 [1.8-2.7] and 5.8 [4.8-7], respectively). Uninsured persons had higher AJBR than insured (HemA, RR 1.8 [1.6-2.1] and HemB, RR 6.9 [5.2-9.]. Table 1 compares characteristics associated with AJBR in multivariate analysis. The use of the FVIII mimetic in persons with HemA was associated with fewer joint bleeds (-1.00 joint bleeds per year). Persons with HemA showed modest decreases in AJBR with EHL therapies (-0.26), a finding not observed in persons with HemB. Worse AJBR outcomes were associated with missed doses for persons with both HemA and HemB. Joint bleeding was significantly associated with unemployment with disability for persons with HemA but not HemB. Trends in AJBR were similar between HemA and HemB for the following: adults had more joint bleeding than children, including adolescents aged 10-19 who are often engaged in team sports; compared with the Northeast, AJBR were higher in all other geographic regions; persons on Government insurance had higher AJBR than persons on Commercial insurance. Discussion: In a multivariate analysis of data on a large longitudinal cohort of persons with severe hemophilia on prophylaxis, use of the FVIII mimetic, ≥90% treatment adherence and treatment in the Northeast United States were associated with significantly lower AJBR. The increased joint bleeding rate in adults compared with children and adolescents may be related to pre-existing joint disease, less intense prophylactic regimens or decreased activity and fitness. Additional studies can further inform optimal hemophilia therapy regimens.

Background Heavy menstrual bleeding occurs in 80% of women with von Willebrand disease and is associated with iron deficiency and poor response to current therapies. International guidelines indicate low certainty regarding effectiveness of hormonal therapy and tranexamic acid. Although von Willebrand factor (VWF) concentrate is approved for bleeds, no prospective trials guide its use in heavy menstrual bleeding. We aimed to compare recombinant VWF with tranexamic acid for reducing heavy menstrual bleeding in patients with von Willebrand disease. Methods VWDMin, a phase 3, open-label, randomised crossover trial, was done in 13 haemophilia treatment centres in the USA. Female patients aged 13-45 years with mild or moderate von Willebrand disease, defined as VWF ristocetin cofactor less than 0 & BULL;50 IU/mL, and heavy menstrual bleeding, defined as a pictorial blood assessment chart (PBAC) score more than 100 in one of the past two cycles were eligible for enrolment. Participants were randomly assigned (1:1) to two consecutive cycles each of intravenous recombinant VWF, 40 IU/kg over 5-10 min on day 1, and oral tranexamic acid 1300 mg three times daily on days 1-5, the order determined by randomisation. The primary outcome was a 40-point reduction in PBAC score by day 5 after two cycles of treatment. Efficacy and safety were analysed in all patients with any post-baseline PBAC scores. The trial was stopped early due to slow recruitment on Feb 15, 2022, by a data safety monitoring board request, and was registered at ClinicalTrials.gov, NCT02606045. Findings Between Feb 12, 2019, and Nov 16, 2021, 39 patients were enrolled, 36 of whom completed the trial (17 received recombinant VWF then tranexamic acid and 19 received tranexamic acid then recombinant VWF). At the time of this unplanned interim analysis (data cutoff Jan 27, 2022), median follow-up was 23 & BULL;97 weeks (IQR 21 & BULL;81-28 & BULL;14). The primary endpoint was not met, neither treatment corrected PBAC score to the normal range. Median PBAC score was significantly lower after two cycles with tranexamic acid than with recombinant VWF (146 [95% CI 117-199] vs 213 [152-298]; adjusted mean treatment difference 46 [95% CI 2-90]; p=0 & BULL;039). There were no serious adverse events or treatment-related deaths and no grade 3-4 adverse events. The most common grade 1-2 adverse events were mucosal bleeding (four [6%] patients during tranexamic acid treatment vs zero during recombinant VWF treatment) and other bleeding (four [6%] vs two [3%]).Interpretation These interim data suggest that recombinant VWF is not superior to tranexamic acid in reducing heavy menstrual bleeding in patients with mild or moderate von Willebrand disease. These findings support discussion of treatment options for heavy menstrual bleeding with patients based on their preferences and lived experience.Funding National Heart Lung Blood Institute (National Institutes of Health).Copyright & COPY; 2023 Elsevier Ltd. All rights reserved.

Long-term efficacy and safety of the extended half-life recombinant factor IX Fc fusion protein (rFIXFc) has been established among previously treated patients with severe hemophilia B in 2 phase 3 trials (B-LONG [#NCT01027364] and Kids B-LONG [#NCT01440946]) and a long-term extension study (B-YOND [#NCT01425723]). In this study, we report post hoc analyses of pooled longitudinal data for up to 6.5 years for rFIXFc prophylaxis. In the B-LONG study, subjects & GE;12 years received weekly dose-adjusted prophylaxis (WP; starting dose, 50 IU/kg), individualized interval-adjusted prophylaxis (IP; initially, 100 IU/kg every 10 days), or on-demand dosing. In the Kids B-LONG study, subjects <12 years received 50 to 60 IU/kg every 7 days, adjusted as needed. In the B-YOND study, subjects received WP (20-100 IU/kg every 7 days), IP (100 IU/kg every 8-16 days), modified prophylaxis, or on-demand dosing; switching between treatment groups was permitted. A total of 123 subjects from B-LONG and 30 from Kids B-LONG study were included, of whom 93 and 27, respectively, enrolled in the B-YOND study. The median cumulative duration of treatment was 3.63 years (range, 0.003-6.48 years) in B-LONG/ B-YOND and 2.88 years (range, 0.30-4.80 years) in Kids B-LONG/B-YOND group. Annualized bleed rates (ABRs) remained low, annualized factor consumption remained stable, and adherence remained high throughout treatment. Low ABRs were also maintained in subjects with dosing intervals & GE;14 days or with target joints at baseline. Complete resolution of evaluable target joints and no recurrence in 90.2% of baseline target joints during follow-up were observed. rFIXFc prophylaxis was associated with sustained clinical benefits, including long-term bleed prevention and target joint resolution, for severe hemophilia B.