Bleeding Disorders Conference

Objective:

There are limited data on the impact of haemophilia on health status and health-related quality of life (HRQL) in people affected by non-severe haemophilia. Aim is to evaluate the health status of people living with mild or moderate haemophilia.

Methods:

A cross-sectional, multinational study was conducted as part of the Patient Reported Outcomes, Burdens and Experiences (PROBE) project. Respondents without bleeding disorder (NoBD) and those with mild or moderate haemophilia were included. Respondents were asked to complete the PROBE questionnaire, which contains haemophilia-related questions, general health questions and HRQL. Results were compared between unaffected individuals and people with mild or moderate haemophilia.

Summary:

A total of 862 respondents, of whom 144 with moderate haemophilia, 143 with mild haemophilia and 575 with NoBD were included. Median age (first-third quartile) was 33 (23-46),42 (25-55) and 43 (35-54), respectively. In relation to bleeding in the previous 12 months, respondents with mild reported less bleeding frequency than those with moderate haemophilia, with similar patterns of bleeding frequency seen in both male and female cohorts. Reporting of acute pain is less in those with NoBD compared to the mild to moderate cohorts for both genders (male - 33%, 67%, 77%; female - 38%, 52%, 67%, respectively). Thirteen percent of those with NoBD reported an impact on activities of daily living compared with mild and moderate haemophilia who reported of 35% and 61%, respectively. The impact on quality of life due to mild haemophilia compared to those with NoBD was a reduction of 5.2%, 5.0% and 9.3% in VAS, EQ-5D-5L and PROBE Score respectively (p≤0.001).

Conclusions:

People affected by mild or moderate hemophilia encountered a significant amount of haemophilia related sequalae. Future research is needed to identify the optimal management of moderate and mild hemophilia patients, with particular focus on early identification of patients with a severe clinical phenotype.

Objectives:

Von Willebrand disease (VWD) is the most common bleeding disorder in children and adolescents. Its varied clinical presentation contributes to challenges and delays in diagnosis and management. We characterized diagnosis, bleeding, and treatment patterns in children (2-11yrs) and adolescents (12-17yrs) with VWD.

Methods:

This retrospective database analysis utilized data from IQVIA PharMetrics Plus Database of medical insurance claims for VWD patients (ICD-9 286.4) from 01/01/2006 to 06/30/2015. Patients included had ≥2 medical claims for VWD and continuous enrollment for ≥2 years, to ensure higher likelihood of definitive VWD diagnosis, before/after their 1st VWD claim. Pre-diagnosis period included 18mos of data before diagnosis. Post-diagnosis period included 7-24mos post-diagnosis data. Data from the first 6-month post-diagnosis period were excluded due to data variability, suggestive of treatment optimization. Descriptive statistics were used to summarize patient demographic/clinical characteristics, including types of bleeding episode (BE), rates, outcomes; treating physician specialty; and type of VWD treatment, in both pre-/post-diagnosis periods.

Results:

475/1087 patients identified were children (43% female; mean age at diagnosis 6.9yrs; 612 were adolescents (74% female; mean age at diagnosis 14.9yrs). The top 3 treating physician specialties seen by children in the pre-/postdiagnosis periods, respectively, were hospitalists (21%/9%), primary care physicians (16%/7%), and hematologists (11%/3%). Adolescents were mostly seen by hospitalists (30%/15%), primary care physicians (25%/16%), and obstetrician gynecologists (19%/15%). 11% of children and adolescents saw a hematologist prior to diagnosis, compared with 3% and 5%, respectively, post-diagnosis. A 17%/15% decrease in bleed claims in the pre-/post-diagnosis period was observed among children (40%/23%) and adolescents (59%/44%), respectively. The most common type of BE among children in the pre-/post-diagnosis periods was epistaxis (19%/10%). Heavy menstrual bleeding was the most common BE among adolescents in both the pre-/post-diagnosis periods (40%/30%; in females 54%/40%). Epistaxis was the second most common BE among adolescents in both the pre-/post-diagnosis periods (11%/7%), and in females (9%/5%), but highest among males (17%/12%). Overall, VWD-related treatment claims increased between the pre-/post-diagnosis periods for both children (12%/23%) and adolescents (31%/50%). The most prescribed treatments for bleed management in children were aminocaproic acid (ACA), desmopressin (DDAVP) and nasal cauterization (pre-diagnosis: 5%, 4% and 4%, respectively; post-diagnosis: 11%, 13% and 3%, respectively). For adolescents, the most prescribed treatments, pre- and post-diagnosis respectively, were oral contraceptives (22% and 33%, DDAVP (9% and 19%) and ACA (4% and 11%).

Conclusions:

This analysis demonstrates a decrease in BE claims following VWD diagnosis and a rise in ACA and DDAVP treatment claims in both children and adolescents, and in oral contraceptive claims among female adolescents. Nevertheless, a considerable proportion of children and adolescents continue to experience BEs 6mos post-diagnosis. This emphasizes the need for treatment optimization and improvement in care and management of patients in these age groups.

Specific guidance is lacking for delivery planning in terms of how high a factor level should be achieved for pregnant women with von Willebrand disease (VWD) who, by the third trimester, do not have von Willebrand factor (VWF) (or factor VIII) levels greater than 50-100%. Specifically, guidance is lacking on whether replacement therapy should target a VWF minimum level in the 100–150% range, i.e., a range closer to the 200–250% levels observed in normal pregnancy.

Objectives:

The primary objective is to document the rate of primary postpartum hemorrhage (PPH) and thereby the effectiveness of targeting minimum VWF levels of 100–150% for delivery.  The secondary objective is to document further effectiveness outcomes and safety.  Patient VWF levels will be maintained at 100-150% for the immediate 72-hour postpartum period, and thereafter maintained at 50-100% target VWF levels through days 5-7 postpartum after normal vaginal delivery or days 7–10 postpartum after caesarean section.

Methods:

This is a prospective, open-label, cohort study of the dosing of Wilate in pregnant patients with VWD to achieve minimum VWF levels of 100–150% for delivery. Outcome parameters will be assessed among patients termed non-correctors and correctors. Patients with a third trimester (gestational week 34–38) VWF level <100% will be enrolled in the non-corrector group. Patients with VWF levels ≥100% at gestational weeks 34–38 will be enrolled in the corrector group.  Sample size is based on 65 pregnant VWD non-corrector patients and up to 30 corrector patients. Both correctors and non-correctors will be given tranexamic acid post-partum for 14 days.

Inclusion Criteria: includes VWD patients diagnosed prepartum as type 1 per NHLBI criterion of VWF level <30%, or type 2, or type 3. Exclusion Criteria includes age <18 years, presence of other concurrent disorder of hemostasis, platelet dysfunction, or collagen disorders; presence of liver disease or renal disease, clinical suspicion or diagnosis of preeclampsia or eclampsia, HELLP syndrome, TTP, DIC, or other acquired vasculopathy or coagulopathy, or inability to perform local laboratory monitoring. Primary outcome parameter will be the rate of primary PPH, defined as estimated blood loss ≥1000 mL, or severe PPH defined as estimated blood loss >2000 mL within 24 hours postpartum. Other outcomes are secondary PPH, laboratory measures, and safety. Screening will begin in Q3 2019 and end in Q2 2023, with recruitment ending 6 months before (i.e., Q4 2022).

Summary:

This planned study aims to determine in VWD if VWF levels postpartum should be attained at levels closer to levels achieved physiologically in a normal pregnancy.

Conclusions:

Results from this study will hopefully lead to reduction of the relatively high rate of PPH in VWD women with levels <50-100% in the third trimester.

Objective:

Evaluate clinical characteristics, hemostasis management, and clinical outcomes regarding menstruation, child birth, surgical procedures, dental care, and spontaneous and traumatic bleeds of women and girls with factor VIII (FVIII; hemophilia A) or factor IX (FIX; hemophilia B) deficiency (WGFD).

Methods:

A retrospective chart review is ongoing at three US hemophilia treatment centers (HTC) to collect data on WGFD (obligate or potential carriers of FVIII or FIX deficiency, with or without genetic confirmation). Data are collected on patients who had at least two HTC visits and underwent medical or surgical interventions for hemostasis management between April 2012 and November 2018, with the outcome available in medical charts.

Summary:

Interim results as of April 5, 2019 include charts from two HTCs on 26 (89.7%) patients with FVIII deficiency and 3 (10.3%) patients with FIX deficiency. The median (range) age at factor deficiency diagnosis was 18.5 (0.1–72.0) years. Twenty-four (82.8%) and 8 (27.6%) patients had a family history of hemophilia and other bleeding disorders, respectively. A total of 17 (58.6%) patients initially visited the HTC due to family history/genetic counseling. Other reasons for visiting an HTC were heavy menstrual bleeding (n=12 [41.4%]) or spontaneous or traumatic bleeds (n=12 [41.4%]), including 7 (24.1%) patients reporting both heavy menstrual bleeding and spontaneous or traumatic bleeds. Of the 12 patients with spontaneous or traumatic bleeds, 4 (33.3%) patients had joint bleeds, 6 (50.0%) patients had excessive nose bleeds, and 9 (75.0%) patients had easy bruising. For those with FVIII deficiency, the median (range) FVIII level at diagnosis was 32.5 (2.0–101.1) IU/dL (n=24), median (range) baseline hemoglobin was 12.9 (5.4–14.8) g/dL (n=19), and median (range) baseline von Willebrand factor ristocetin cofactor was 70 (40–150) IU/mL (n=16). The median (range) number of documented bleeds was 1.0 (0.0–24.0) in the first year at the HTC. Final results of this chart review, including data from those with FIX deficiency, HTC interventions, and outcomes for hemostasis management, will be presented.

Conclusions:

This chart review provides further insights into the clinical presentation and hemostasis management of WGFD evaluated at HTCs in the US. Results may contribute to the design of future prospective studies evaluating treatment options for this patient group.

Background:

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative or qualitative deficiency of the protein, von Willebrand factor (VWF). There is a lack of clear guidance on best practices to inform the care of people with VWD.

Objectives:

Identify and prioritize the main topics of a collaborative guideline development effort.

Methods:

A scoping survey to prioritize topics to be addressed in a collaborative guideline for VWD was distributed to international stakeholders including patients, caregivers, clinicians, and allied healthcare professionals. The distribution strategy was coordinated by the guideline chairs and representatives of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH). The survey was conducted in English, French, and Spanish. The survey focused on both diagnosis and management of VWD, using 7-point Likert-scale response options and open ended comments. Descriptive analysis of participants and comparative analysis of results by stakeholder subtype (patients/caregivers versus healthcare providers [HCP]), gender, and income setting was performed. Qualitative conventional content data was analyzed utilizing both deductive and inductive coding processes.

Results:

601 participants responded to the survey (49% patients/caregivers, and 51% HCPs). The highest priority topics identified were diagnostic criteria/classification, bleeding assessment tools, treatment options for women, and surgical patients. In contrast, screening for anemia and plasma-derived therapy versus recombinant therapies were rated the lowest priority topics (figures 1 – 2).

Conclusion:

The survey results highlighted areas of importance in the diagnosis and management of VWD across diverse groups of stakeholders and will direct future guideline efforts. The large number responses (601) and discrete comments (9,500) attest to the interest and involvement of the VWD community in this effort.
 

Objective:

While a new generation of therapies for patients with Hemophilia A are available, it is unclear what patient characteristics, perceptions, and barriers are associated with the decision to switch FVIII replacement therapies. This study assessed patient characteristics, health history, and reasons for switching from a FVIII product with more frequent dosing (³3x infusions/week) to a product with less frequent dosing (≤2x infusions/week) from patient/caregiver and physician perspectives.

Methods:

Data collection was a mix of qualitative and quantitative procedures. The qualitative portion consisted of two online discussion forums: patients (n=17) and caregivers of patients (n=11) receiving a FVIII product dosed ³3x/week, and patients (n=22) and caregivers of patients (n=5) who switched to a product dosed ≤2x/week. The quantitative portion was a retrospective medical chart review (n=207) which captured variables (e.g., bleed rate, treatment history) 6 months pre- and 6 months post-switching to a product with less frequent dosing.

Summary:

Prominent drivers among patients for starting a FVIII product with less frequent dosing included: 1) experiencing diminished effectiveness while on a product dosed ³3x/week resulting in increased breakthrough bleeding, 2) experiencing vein access issues, and 3) beginning prophylaxis as opposed to on-demand infusions after a bleed.

Key barriers to changing included: 1) fears regarding the process of switching being complicated, time consuming, and costly, 2) perceived risks associated with switching, and, 3) possible lack of healthcare provider support.

Physicians were most likely to report that patients switched products because they sought a newer product with twice weekly dosing or less per FDA-approved dosing recommendations (35.3%), followed by patient requested the switch (30.4%), and patient sought a reduction in infusion frequency to improve adherence (27.5%).

Switching to a product with less frequent dosing was associated with improvements in patient-reported bleeding-related outcomes. Patients were more likely to self-administer the treatment post-switch (63.8%) compared with pre-switch (48.8%; p<0.001) and had fewer infusions per week post-switch (2.8 vs. 3.3; p<0.001). Patients’ annualized bleed rate was lower (5.9) post-switch compared with pre-switch (7.7; p<0.001).

Both the number of spontaneous joint bleeds and joint bleeds after trauma or injury were lower (3.2 and 2.7) post-switch (3.6 and 4.3; p=0.044 and p<0.001). The bleeding event was less likely to be classified as moderate or severe (34.5% and 5.9%) post-switch compared with pre-switch (55.0% and 10.0%; p<0.001 and p=0.049). Fewer infusions were required to resolve the bleeding event post-switch (2.6 vs. 3.2; p<0.001).

Conclusion:

A prominent reason why patients switch treatment is to improve bleeding-related outcomes. Indeed, we found that switching to a FVIII product with less frequent dosing was associated with improved patient-reported bleeding-related outcomes. These findings are critical for improving patient outcomes and support the FDA mandate to incorporate patient perspectives in the regulatory process.

Background:

US Hemophilia Treatment Center (HTC) care reduces mortality and hospitalizations, and guidelines recommend this care model.  Yet national data that uniformly and longitudinally monitors patient experience with HTC care is limited.

Objective:

To assess patient satisfaction with HTC services and clinicians over time.

Methods:

The US HTC Network conducted the first ever nationally uniform patient satisfaction surveys on care received in 2014 and 2017. A Regional workgroup devised, piloted, and finalized an electronic, two-page survey for self-administration at clinic, or at home, in English or Spanish. Content was based on national instruments to enhance comparability and scientific robustness. Questions assessed demographics; satisfaction with HTC team members and services; insurance and language barriers. Respondents were anonymous but identified their HTC.  Participation was voluntary.  Patients with HTC contact in 2014 and 2017 were eligible. Data were collected for 4 months in 2015 and 6 in 2018; on average 130 HTCs (94%) from all US regions participated. Parents completed surveys for children under age 18. Data were entered, analyzed and aggregated at national, regional and HTC levels at a central site.

Results:

5006 and 4767 persons participated, respectively, in 2015 and 2018.  In both years, over 1400 (30%) respondents were female, nearly 80% were White, and 10% Hispanic. On average, 3038 had Factor 8 or 9, 1280 Von Willebrand, 186 other factor deficiencies and 369 other bleeding disorders.  Respondents reported being ‘always’ or ‘usually’ (A/U) satisfied with HTC staff and services from 90% - 97% of the time in both 2014 and 2017. In both years, >4400 gave these highest A/U ratings for HTC Hematologists and Nurses; 3300 for Social Workers; >2600 for Physical Therapists; 1400 for Genetic Counselors, and >1100 for Psychologists.  In both years, 96% were A/U satisfied overall with HTC services. Over 95% gave the A/U satisfaction ratings both years for these services: getting needed care and information, being treated respectfully, spending sufficient time with staff, and involved in shared decision making. 82% and 91% of respondents, respectively, gave the A/U satisfaction ratings for care coordination with primary care providers and other specialists.  Over 90% of >700 youth age 12-17 gave HTC teen transition services the A/U satisfaction ratings both years. 96% of >2760 respondents reported A/U satisfaction with their HTC Pharmacy (340B) Factor Program in 2017. Insurance and language barriers to HTC care posed problems A/U for 27% and 15%, respectively both years.

Conclusions:

Patients consistently report high levels of satisfaction with HTCs, documenting HTC value over time.  Patient satisfaction influences treatment adherence, can influence reimbursement, and is increasingly required by payers. A national uniform survey is feasible to conduct using a regional structure to implement, is well received by patients, and provides critical information to stakeholders.
 

Helping teens with bleeding disorders prepare to manage their care as they transition to adulthood is a national priority for US Hemophilia Treatment Centers (HTC).  The National HTC Patient Satisfaction Surveys (PSS) reveal high satisfaction with HTC teen transition services. Yet how satisfaction differs comparing HTCs that primarily care for children to HTCs that care for patients throughout the lifespan is unknown.

Objective:

To assess variation in patient satisfaction with US HTC teen transition services by HTC type.

Methods:

The US HTC Network conducted nationally uniform patient satisfaction surveys in 2015 and 2018 on care received, respectively, in 2014 and 2017. A Regional workgroup devised, piloted, and finalized an electronic, two-page survey for self-administration at clinic, or at home, in English or Spanish. Participation was voluntary.  Respondents were anonymous but identified their HTC. Parents completed surveys for children under age 18. The PSS included two teen transition questions for respondents age 12-17 to complete. HTC type was categorized as ‘pediatric’ if >80% of responses were from patients/caregivers of individuals under age 18, and ‘adult’ if >80% were from patients over age 24.  All other HTCs were categorized as ‘lifespan’.  For both years, approximately 26% of HTCs were classified as pediatric, 52% as life-span, and 22% as adult.

Results:

Over 700 teens age 12-17 (or their parents/guardians) from an average of 130 HTCs (94.0%) from all US regions participated in 2015 and 2018. Approximately 96.5% of teens at pediatric HTCs (96.4% - 96.5%) and 96.2% at lifespan HTCs (95.9% - 96.5%) reported being ‘always’ or ‘usually’ (A/U) satisfied with HTC services overall.  On average, 90.4% of teens at pediatric HTCs (90.1% - 90.7%) and 91.0% at lifespan HTCs (90.3%–91.6%) reported being A/U satisfied with how HTC clinic staff talked about how to care for the bleeding disorder as they became an adult. Similarly, 92.5% (92.0%– 92.9%) of teens at pediatric HTCs and 92.5% (92.3%-92.7%) reported being A/U satisfied with how the HTC clinic staff encouraged them to become more independent in managing their bleeding disorder. 

Conclusions:

HTC patients age 12-17 years consistently report very high levels of satisfaction with HTC teen transition services, regardless if the HTC primarily cares for patients up to age 17, or throughout the life-span.  This suggests teens receive support and tools to successfully transition to adult care across the US HTC Network.  A national uniform HTC Patient Satisfaction Survey provides vital information, is feasible to conduct using a regional structure, and well received nationwide.
 

Objective:

Hemophilia may negatively impact a patient’s health utility and quality of life (QoL). Health state utility values (HSUVs) and QoL are important inputs to the evaluation of novel treatment being developed in hemophilia, including gene therapies. This systematic literature review identified and evaluated HSUVs and QoL for people with hemophilia (PWH) type A and/or type B, as well as utility decrements relevant to the experience of PWH, by treatment and health state.

Methods:

Building on a review undertaken in 2014 (Grosse et al. 2015), we conducted a systematic literature review to March 2019 through a search of electronic medical databases, including MEDLINE®, Web of Science, Cochrane Library databases and the School of Health and Related Research Health Utilities Database (SCHARRHUD). Major clinical, patient, and pharmacoeconomic conferences in 2016-2019 were also queried. Studies were independently double screened by independent reviewers, after which data extraction was performed.  The information extracted included study design, description of treatment and health state, respondent details, instrument and tariff, HSUV and QoL estimates, quality of study, and appropriateness for use in economic evaluations of novel treatment.

Summary:

Of 1,511 titles and abstracts screened, 20 studies and 12 conference abstracts were included. The studies identified applied a mix of direct and indirect health utility elicitation techniques. Two studies applied direct time trade-off (TTO) methodology and the remaining 30 studies adopted indirect valuation methodologies. HSUVs were found to decrease with increasing disease severity. For example, in Hoxer et al. (2018), mean (standard deviation) HSUV were 0.80 (0.21), 0.73 (0.22) and 0.67 (0.25) in people with mild, moderate, and severe hemophilia, respectively.

Utility values were also found to vary by severity of musculoskeletal damage, frequency of bleed episodes, inhibitors, hemophilia subtype, treatment regimen, treatment adherence and other disease-related complications. Interestingly, HSUVs derived from valuations from the general public were found to be valued lower than those derived from PWH for similar health states. For example, in Carlsson et al. (2017), general population participants consistently rated significantly lower HSUVs for hemophilia disease states compared to PWH (range: 0.54-0.60 vs. 0.67-0.73).

Several hemophilia-specific QoL instruments were used alongside HSUV evaluations. These QoL findings further contribute to improving the understanding of the impact of hemophilia on PWH.

Conclusions:

This systematic review shows significant impact of hemophilia on health utilities and QoL among PWH. The substantial humanistic burden experienced by PWH highlights unmet needs remaining in hemophilia. Our review findings also suggest potential disease state adaptation among PWH, which warrants further research using robust patient preference studies.
 

Objective:

The National Hemophilia Foundation Education team partnered with an evaluator to conduct a needs assessment of the rare bleeding disorder (RBD) community to help inform the development of programming tailored to the community’s unique experiences and needs.

Methods:

A guided discussion with the attendees of a Bleeding Disorder Conference (BDC) session titled, “The Lonely Island: Dealing with Being Rare” in 2018 as well as brief surveys at the end of the session were compiled as part of the needs assessment. Additionally, 12 one on one interviews of those part of the RBD community (either affected themselves or a close relative to someone that is affected) were conducted.

Summary:

Various challenges for this population were identified, including: connecting with others who have the same RBD; healthcare providers’ lack of knowledge/understanding of specific RBDs; accessing knowledgeable hematologists and RBD experts; accessing the latest science specific to their RBD; scarcity of treatment resources; difficulty getting diagnosed. Other secondary challenges were also expressed. While challenges were identified, those that participated in the needs assessment also highlighted the ways in which they see the RBD community can best be served. Common suggestions included: the addition of RBD-specific programming at NHF’s Bleeding Disorder Conference (BDC); continuing to make NHF and Chapters inclusive; creating more opportunities for the RBD community to connect with others with the same RBD (at NHF’s BDC and other events); creating targeted educational materials and opportunities for the RBD community; creating opportunities for members of the RBD community to identify and engage with the medical community.

Conclusions:

By conducting this needs assessment, NHF took an important step in asking the RBD community directly how they can best be supported given their unique experiences and needs. While challenges for the RBD community were identified, several opportunities to support the RBD community were also identified.
 

Objective:

To determine the medical and educational needs reported by persons with Type 3 and other severe types of Von Willebrand Disease (VWD) who attended the second USA National Type 3/Severe VWD Conference held in Florida in June 2018.

Little research has been done concerning medical issues and education in Type 3/Severe VWD.  As patient identification increases, it is vital that education, support and resources are available for these patients.

Methods:

A survey of 48 questions was developed and administered to 74 vetted patient attendees. Responses for any individual question varied between 62-66.  The survey was administered through an Audience Response System (ARS) utilizing handheld clickers. The responses were compiled and immediately visually available to the respondents via a projector screen.

The multiple-choice questions were used to identify basic demographics, medical and psychosocial concerns, and educational needs.

Summary:

In this self-reported ARS survey, basic demographic data was obtained. This sample of VWD patients reported a need for more education on several issues related to their medical and psychosocial issues including depression/mental health issues, lab results and product choices. In addition, subjects reported significant needs for care, treatment and education in the fields of orthopedic services and genetic counseling.

Respondents' answers expressed a lack of orthopedic care despite a need for it. Only 8 (13%) patients reported having an orthopedic surgeon attend his/her bleeding disorder clinic. Forty-two (67%) did not know of any orthopedic resources. However, 18 (28%) reported that he/she had already had at least one joint surgery/procedure due to VWD and 5 (*%) plan to have surgery in the future. Eight (12%) had had joint replacements. 

Only 25 (40%) of respondents knew that they had undergone genetic testing related to their bleeding disorder, 30 (48%) have not had genetic testing, 8 (13%) were unsure.  When asked, “Were your parents diagnosed with a bleeding disorder before your birth?” of the 63 who answered, 51 (81%) stated “no, neither parent”. When asked if a parent was diagnosed with a bleeding disorder after the respondent’s birth, 24 (38%) responded “yes” to one or both parents. Twelve (19%) respondents have had their diagnosis change since first being identified with a bleeding disorder.

Conclusion:

Orthopedic care, genetic testing and education are vital services wanted by Type 3/Severe VWD patients. The community should further evaluate these needs and take action to respond. These results may also empower persons with Type 3/Severe VWD to seek support from professional and social members of their community. 
 
 
 

Objective:

To investigate how bleeding disorder characteristics influence patient perceived challenges and management strategies.

Methods:

This is a mixed-method, retrospective, cross-sectional continuation of a pilot study identifying themes of self-perceived challenges and management strategies for persons with bleeding disorders. Sixty-one participants with a bleeding disorder (BD), either hemophilia (PWH) or Von Willebrand disease (PWVWD), were asked what their most significant challenge was in managing their BD and how they managed that challenge. Data were collected from March, 2017 through December, 2018, coded for themes and uploaded to NVivo. Similar themes were grouped for analysis. Subject-level data was extracted from the electronic medical record including demographics, disease type, severity and presence of joint disease (JD).  Pain interference was determined from participant response to the Brief Pain Inventory (BPI). 

Results:

• The mean age of the cohort was 31.4 years, with a median of 25 years, and range of 7 to 75 years. 87% were PWH, 13% PWvWD.
• There were 26% mild, 25% moderate, and 49% severe PWH.
• 54% had JD.
• Identified challenges included: participation restriction (24%), acute bleeding (22%), infusion (19%), bleeding sequelae (10%), other’s unfamiliarity with bleeding disorder (other’s unfamiliarity) (10%), no challenges (10%), and other (6%). Management strategies reported were: acceptance (37%), learning through experience (25%), education/advocacy (11%), seeking help (9%), other (9%), and no challenges (9%).
• Severe PWH greatest reported challenges were participation restriction (27%) and infusion (27%).  Management strategies were acceptance (41%) and experiential learning (31%).
• Mild-moderate PWH greatest reported challenges were acute bleeding (35%), infusion and no challenge (17% each). Management strategies were acceptance (30%) and seeks help (26%).
• Seek help was not identified as a strategy among severe PWH.
• Reports of no challenges was higher among those <18 years than those ≥ 18 years.
• Mean pain interference was 13.2 out of 70 based on the composite score of BPI measures.
• As age increased, the likelihood of JD and interference increased.
• Regardless of challenge, people with JD reported interference averaging 18% (range 0-27%).

Conclusions:

Gaining insight to patient-perceived challenges and management strategies is important to be able to tailor an effective treatment approach that is individualized and meets the changing needs of PWBD across circumstance and life-course.

Introduction:

Photovoice is a qualitative research method that has been used for communities to share pictures as a tool for discussion that is often used at a grassroots advocacy level. Photovoice can show both strengths about a topic or concerns. Photovoice can create empowerment by sharing perspectives and can also create a foundation to advocate for awareness and change.

Long-term Goal:

To create more awareness surrounding bleeding disorders during the month of March, which is bleeding disorders awareness month.

Objectives:

1. To apply Photovoice methodology to the use of social media among the hemophilia population in the Cincinnati, Ohio geographical area.
2. To engage people with hemophilia and their families in sharing their stories related to their bleeding disorder by sharing photographic images on social media during bleeding disorders awareness month.

Methods:

People that follow the Tri-State Bleeding Disorder Foundation on social media as well as members of a closed social media group that consist of parents of children who are patients at Cincinnati Children’s Hospital were asked to participate in the pilot Photovoice project. Participants were asked to share pictures on their own social media pages and to use hashtags to link the photos to the Tri-State Bleeding Disorder Foundation’s page. The project was promoted by sharing an infographic that explained Photovoice and the details of the project. Several community stakeholders were identified as people active on social media and they were personally asked to participate so that examples of the project could be shared with others. There were weekly themes and a weekly contest for pictures that best exemplified that week’s theme with the winners winning a small gift card.

Summary:

This innovative pilot project applied the methodology of Photovoice to social media to generate awareness and advocacy during bleeding disorders awareness month. The theme of this Photovoice project was “Living with Hemophilia”. Weekly themes consisted of: living with a new diagnosis, living with treatment, living and learning about a bleeding disorder, and living with health and being physically active.

Conclusion:

Utilizing Photovoice and applying this methodology to social media as a pilot project with the bleeding disorder population is an innovative idea. This grass roots level movement is a modern way for people to share their story of living with a bleeding disorder. To date, the use of this methodology with the bleeding disorder population has not been documented in the literature. Participants in this project reported satisfaction with being a part of the project. The project’s authors reported that it was a positive and creative way to create more awareness on a personal level about bleeding disorders and they plan to repeat the project in the future. 

Objective:

Persons with bleeding disorders experience pain in association with needle pokes, joint and muscle bleeds and permanent tissue damage.  The impact of this pain on patients can include time off school or work, a change in career, income, stress, mental health concerns and change in relationships.  Comprehensive pain management includes strategies from the “Four P’s of Pain Management” which include pharmacological, physical, psychological and prevention.

The aim of the project was to examine current psychological knowledge and management of pain within our patient population.  This study asked the following research questions: 1) What is currently understood about pain and bleeding disorder care among social workers (CSWHC)? 2) What specific pain knowledge and training is prioritized by social workers in Hemophilia Treatment Centres?

A scoping review was conducted concurrently with the qualitative study.  Medline and SocIndex were searched with the terms “social work” and “pain management” and a second search was conducted with the term “social work and hemophilia/von willebrand's or platelet disorders”.  A total of 105 articles were examined by three independent reviewers. Eleven articles have been included for the purpose of examining the role of social work in pain management.

Methods:

Qualitative interviews were conducted and recorded with 12 social workers from the CSWHC between September 2018 and February 2019.  Five provinces were represented. Social work participants were deployed within paediatric, adult or within combined clinics. The interviews were approximately 20-45 minutes.  Transcribed interviews were coded with NVivo by two independent reviewers with Thematic Analysis.

Summary:

Social workers identified the roles of social work to include completion of psychosocial assessments and meeting the practical needs of patients, while supporting patients in medical decisions.  Barriers to pain management and the impact of pain on patients were described as having an impact on individuals and families. Social workers also discussed their understanding of acute and chronic pain in patients, which has indicated an increase of knowledge is required.  Skills development in multi-dimensional nature of pain and pain assessment were determined to be most likely to produce positive impact on practice outcomes. Initial themes include hope, relationship of trust, stigma (diagnosis vs. pain), defining multidisciplinary roles.

Conclusion:

Study results, first, will contribute to the literature supporting the need for social work education for those practicing in bleeding disorder care.  Secondly, they will provide recommendations for an educational pain curriculum for social workers in bleeding disorder care. This education will reflect the need for pain knowledge in acute and chronic pain dimensions which will facilitate dialog with other professionals in pain management.  Pain assessment will also be a focus in order for social workers to be able to support and provide appropriate referrals for pain management.

Objective:

To examine the frequency and methods used to screen patients for substance use and behavioral health disorders in Hemophilia Treatment Centers (HTC). We hypothesized that inconsistencies in methods utilized and frequency of utilization exist.

Methods:

Marshall University (MU) Physical Therapy faculty along with MU addiction education staff developed a 26-question survey using Qualtrics. The survey included questions on demographics, validated screening tools utilized, screening frequency, and team member responsible for screening. The HTC email addresses were obtained from the Hemophilia Treatment Center Directory on the CDC’s website. Following approval from MU IRB, the survey was disseminated via an online link. Descriptive analysis was performed on the data.

Summary:

Health professionals from 19 HTCs, representing 8 different regions, completed the survey. The overall response rate was 13.6%. Social workers (12, 63.2%), nurses (6, 31.6%)) and counselors/psychologists (1, 0.05%) submitted responses. On average HTCs reported 34.5% (0-92%) of their patients experience chronic pain with an average 22.4% (0-56%) receiving prescription opioids for pain management. Adverse consequences related to opioid use existed in all of the HTCs including overdose (31.5%), withdrawal symptoms (42.1%), increased dose due to tolerance (63.2%), and increased bleeding episodes (26.3%). The majority of HTCs (57.9%) reported being the primary provider of pain management for people with hemophilia (PWH). Standardized screening for substance use disorders is occurring 31.6% of the time with marijuana and illicit drugs (100%) being most commonly screened followed by alcohol and prescription drugs (83%) and tobacco at 33%.  Frequency of screening for substance use varied widely from every comprehensive visit to initiation of an opiate contract to suspicion of misuse. Screening for behavioral health is more common (81.3%) with a variety of validated screening tools being utilized. Over 60% of the time, screening for anxiety and depression occurs either annually or every visit.

Conclusions:

PWH often develop chronic pain related to joint arthropathy.

Based on our findings, the incidence of chronic pain in PWH is relatively equal to the national average. HTCs are often the primary provider of pain management and are challenged to find safe treatment methods. PWH are often prescribed opioids which may place them at increased risk for potentially developing an opioid use disorder.

The presence of a behavioral health disorder may further enhance one’s risk. Although behavioral health screenings appear to be more consistently utilized in HTCs, substance use screenings are rare. Our research suggests that universal screening for substance use and behavioral health conditions should be considered, as a standard of care in HTCs, to better inform healthcare providers of patient risk, need for referral and to guide prescriber’s decision making with regard to pain management options. 
 

Objective:

Report on the utilization of a multi-point videoconferencing platform, Extensions for Community Healthcare Outcomes (ECHO), in providing a clinical learning opportunity to physical therapists (PTs) involved with people with bleeding disorders (PWBD) within Western States Region Hemophilia Treatment Centers (WSR HTC).

Methods:

WSR HTC includes thirteen HTC’s located in California, Nevada, Hawaii, and Guam. Monthly one-hour evidence based case presentations with a facilitated discussion were conducted using the ECHO platform. Each session was recorded, so all the therapists invited to participate have access to the information.

Data were collected from the WSR participating PTs by using anonymous on-line surveys, Qualtrics software (Qualtrics, Provo, UT), and prior to the start of the physical therapy ECHO session and upon completion of each session.

Descriptive statistics were calculated to evaluate the educational value of presentations.

Results:

Thirteen PTs, surveyed prior to the first PT ECHO session had reported  > 6 years of experience as a PT. Twenty-three percent reported < 5 years of experience working with PWBD and over half of PT surveyed had > 16 years of experience working with PWBD.

Eight topics were presented in 2018 included musculoskeletal ultrasound imaging, invasive surgery rehab outcomes for patients with inhibitors, kinesiology taping, knee arthroplasty and stiffness, iliopsoas bleeding, myofascial decompression, chronic pain, knee bleed, and ankle joint impact from bleeding. An average of nine HTC PTs attended each session (range 4 to 18). Ten (11.2%) non-HTC PTs (outpatient PTs, HTC nurse, HTC Nurse Practitioner) attended some of the PT ECHO sessions. Table 1.

Ninety-five percent of respondents reported strong agreement with the program’s educational value and appropriateness for a practicing PT. Thirty-seven (94.9%) of responses reported agreement that the PT ECHO program improved their knowledge of physical therapy and bleeding disorders. Table 2.

Conclusion:

Videoconferencing platforms such as ECHO allows PTs in the WSR HTC, who are geographically separated to successfully share clinical knowledge to facilitate best practice in the area of specialty care for PWBD.
 
Please see files attached for tables and figures.
 
 
 

Background:

There are no reported cases of acute lymphoblastic leukemia (ALL) in patients with hemophilia B. There is one case report of a young adult with hemophilia B and acute myeloid leukemia (1). Currently, there is no best practice recommendation for the management of patients with hemophilia B and ALL.

Objectives:

To report our experience in managing a pediatric patient with congenital hemophilia B and ALL, which presents a rare and unique clinical challenge.

Design/Method:

Retrospective chart review

Results:

This is a 2y/o male with hemophilia B diagnosed at birth from a cord blood sample showing a factor IX level <1%. Mother is a known carrier and maternal grandfather has severe hemophilia B. Patient started prophylaxis with a standard half-life product through central venous access around 8months of age, following a spontaneous wrist bleed. The schedule was 35 units/kg twice a week. He had no spontaneous joint or soft tissue bleed on this regimen. 3mo ago he presented with pain and swelling of the right wrist. He fell on an outstretched hand the day before and received 100% factor infusion. X-ray showed metaphyseal lucencies with overlying soft tissue swelling. No evidence of fracture. Due to this finding, additional labs were done. WBC 4.8K, hemoglobin 7.1 g/dL, platelets 18K and 31% blasts. Flow cytometry confirmed the diagnosis of preB-ALL. On exam, he had pallor, scattered petechiae and cervical lymphadenopathy.

Based on recovery studies and thrombocytopenia, the prophylaxis was changed to 50 units/kg every third day. The platelets are kept above 30K at baseline. For lumbar punctures, he has been corrected to 100% factor level and platelets kept above 50K. However, due to the risk of port infection with frequent accessing, he was switched to long-acting albumin fusion factor IX product on day 22 of induction. The current prophylaxis regimen is 75units/kg weekly and the schedule is adjusted to coincide with lumbar puncture days whenever needed. He has tolerated all his procedures well without increased bleeding, including end of induction bone marrow aspiration, biopsy and lumbar puncture with intrathecal chemotherapy. He is currently in remission and is in interim maintenance phase of treatment per COG protocol AALL0932.

Conclusion:

Long-acting factor IX products could potentially decrease the number of infusions and need for frequent central venous access in immunocompromised patients with hemophilia B. In addition, a higher trough level with a weekly schedule could provide better bleed control in patients with severe thrombocytopenia due to underlying malignancy. A baseline platelet count of at least 30K is recommended during treatment. More treatment guidelines need to be established.

(1) Clark C et al, Pediatric Blood and Cancer Jan 2011

Objective:

NHF Chapters must develop, support, and sustain influential advocacy programs to protect and enhance access to health care for the bleeding disorders community.

Method:

NHF supports the development of state health care policy advocacy programs with in-kind and financial assistance. NHF’s State-Based Advocacy Coalition (SBAC) program and the standard advocacy expectations our Chapters are the pillars of a robust framework of state advocacy programs. The standard advocacy expectations provide clear expectations and identify best practices for advocacy programming. These include: an advocacy committee of staff and volunteer advocates that meets monthly, multi-year strategic planning, clear engagement with legislative and administrative policymakers, an advocacy annual budget, and more. Chapters are also expected to actively engage their network of Hemophilia Treatment Centers, and all Industry partners.

The SBAC program provides funding and in-kind support from NHF for chapters to either start an advocacy program or grow and maintain an advanced one, using the standard advocacy expectations as a guide. NHF provides extensive in-kind support for SBAC grantees, as well as assisting all other chapters with their specific advocacy needs.

Summary:

Since the inception of the SBAC program NHF has seen participation by and enthusiasm among community members in advocacy events and programming grow. Nearly 500 volunteers participated in NHF’s Washington, DC Days in recent years. Chapter run State Advocacy Days are more prevalent and well-attended. At least 1000 advocates now travel to their state Capitol each year to participate in chapter Advocacy Days. There are 15 grantees participating in the SBAC program covering 20 states. Collectively, NHF has trained more than 5,000 volunteer advocates across the country.

Increasing numbers of volunteer advocates have turned out in state capitols for several years to make their voices heard and influence health care access. In addition, NHF’s investments in public policy resources have allowed us to encourage and support state regulatory advocacy, e.g. with state Medicaid offices. These new efforts have demonstrated tangible results in the form of protecting and enhancing patients’ access to care.

The promotion and support of state chapter advocacy programs by NHF, especially among the SBAC-participating states, has advanced the public policy interests of the bleeding disorders community. Objectively, we’ve seen the increased numbers and enthusiasm of volunteer advocates. Anecdotally, there are many stories of chapters playing a key role in state health care policy,

Conclusion:

Successful state advocacy work has led to improved access to quality healthcare. Start-up and ongoing support from NHF have played a critical role in that success. The continued refinement of our Chapter standard advocacy expectations and in-kind support of NHF policy staff will continue to be key to advancing state advocacy programs uniformly around the country.

Objective:

The formation of inhibitors to clotting factors is a serious complication in hemophilia A. Immune tolerance induction (ITI) therapy remains the primary method for eradicating inhibitors. This multicenter retrospective data collection project evaluated patient- and treatment-related factors associated with outcomes following primary or rescue ITI with an antihemophilic factor (Human) concentrate in patients with hemophilia A and high titer inhibitors.

Methods:

Medical records of nine inhibitor patients treated with antihemophilic factor (human) for primary or rescue ITI therapy between January 1, 2012 and July 31, 2017 were evaluated in four US hemophilia treatment centers. Data were de-identified and analyzed descriptively. Outcome measures were defined per the International Immune Tolerance Induction Study: successful (eradication of FVIII inhibitor and normal FVIII recovery), partial success (near normal FVIII recovery), and failure.

Results:

A total of nine patients between the ages of 10 months and 39 years at time of ITI were evaluated. Six out of nine patients (66.7%) had successful ITI; three with complete success (ages 27, 32, 32 years) and three with partial success (ages 5, 5, 21 years). Three patients failed ITI (ages 1.5, 10.5, 39 years) (Table 1.) Six of the patients had a combined previous ten attempts at ITI with other products (plasma derived and/or recombinant). Of these six rescue patients, ITI with antihemophilic factor (human) was successful in one and partially successful in three.

Conclusions:

While retrospective data has limitations, real-world evidence demonstrates that ITI with antihemophilic factor (human) concentrate can be successful or partially successful in diverse populations of moderately complex patients with hemophilia A and high titer inhibitor.

 

Objective:

Immune tolerance induction (ITI) is the standard of care for inhibitor eradication and restoration of factor VIII (FVIII) responsiveness in subjects with severe hemophilia who develop high-titer inhibitors. Retrospective data support the use of recombinant FVIII Fc fusion protein (rFVIIIFc) in ITI (Carcao et al. Haemophilia. 2018) but this has yet to be confirmed in prospective studies. This study presents preplanned interim results of verITI-8 (NCT03093480).

Methods:

VerITI-8 is a single-arm, nonrandomized, open‐label, ethics-approved study of rFVIIIFc (200 IU/kg/day) for first-time ITI. Eligible subjects had a history of high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL) and provided informed consent. The primary endpoint is time to tolerization, defined by negative inhibitor titer (<0.6 BU/mL) at two consecutive visits; incremental recovery ≥66% of expected at two consecutive visits; and rFVIIIFc half‐life ≥7 hours. ITI failure is defined as not meeting the above criteria by Week 48. This interim analysis was planned when ≥10 subjects had received ≥6 months of rFVIIIFc ITI.

Summary:

Fifteen subjects were screened as of the December 5, 2018 cutoff, while 14 subjects enrolled and had received ≥1 dose of rFVIIIFc for ITI. The median (range) age at start of ITI was 2.6 (0.8–16.0) years and historical peak inhibitor titer was 29.6 (6.2–256.0) BU/mL. Six subjects have been successfully tolerized, with a median (range) time to first negative titer, normal incremental recovery, and tolerization of 2.3 (1.7–15.6), 6.0 (4.3–28.1), and 11.7 (8.1–32.0) weeks, respectively. Seven subjects continue to receive rFVIIIFc ITI (median [range] time on ITI: 16.0 [0.1–35.6] weeks) and 1 subject has failed. No adverse events related to rFVIIIFc have been reported.

Conclusions:

Early results from this prospective/ongoing study of first-time ITI indicate that rFVIIIFc may offer rapid time to tolerization in some subjects with severe hemophilia A and high-titer inhibitors. Achieving tolerance faster can improve quality of life and reduce costs.
 

Objective:

Acute bleeds in patients with rare bleeding disorders (RBDs), including congenital hemophilia with inhibitors (CHwI), acquired hemophilia, congenital factor VII deficiency, and Glanzmann’s thrombasthenia (GT) must be treated as quickly as possible. This study evaluated the obstacles and experiences of patients with CHwI, or their caregivers, for the early treatment of acute bleeds in non-hemophilia treatment centers (HTCs).

Methods:

Patients in the United States (aged 18–65 years [or caregivers of patients <18 years]) with CHwI, who currently have or have had inhibitors in the last 3–4 years, and who sought treatment in a non-HTC, underwent an interactive online qualitative discussion over 7 days.

Summary:

The survey was completed by 23 respondents (seven patients and 16 caregivers; all patients with CHwI). Respondents were aware of the need to treat bleeds quickly, which had been taught to them by physicians and learned from experience. Delays in respondents initiating their treatment were typically due to: technical issues (e.g., 7/23 respondents had difficulty gaining access to a vein or port); delay in diagnosis (e.g., 5/23 respondents’ child does not inform caregiver of the bleed); convenience (e.g., 3/23 respondents were unwilling/unable to take treatment out of the home); or financial issues (e.g., one respondent had inadequate insurance). Respondents tended to visit a non-HTC as a last resort, often due to the long distance to an HTC when emergency treatment was needed, unsuccessful pain management, or unsuccessful factor administration at home. Most patients/caregivers (20/23) reported treatment delays in emergency departments (EDs). Delays in EDs were often due to healthcare professional’s (HCP) lack of knowledge (16/23 respondents; 4 hours average wait until treatment) and four reported delays due to lack of available treatment (14 hours average wait for treatment). All patients/caregivers reported that they had dealt with uneducated/unaware HCPs, having to spend significant time educating the ED staff. Three respondents reported not waiting for treatment—partly because they chose hospitals very carefully, and because they had educated their closest hospital prior to needing an emergency service. Patients/caregivers with negative experiences reported that HCPs were unwilling to listen to them, did not seek consultation quickly, dismissed their instructions, and directed care that forced an outcome. When patients had satisfactory experiences, HCPs listened intently, immediately called an HTC/patient’s physician, and provided care in consultation. Respondents highlighted the need for HCPs education on hemophilia.

Conclusions:

Patients/caregivers are aware of the need to treat an acute bleed fast, but sometimes delay their treatment, and experience delays when attending non-HTCs. The lack of experience of HCPs in managing acute bleeds contributes to these delays. Improved education of HCPs at non-HTCs and provision of protocols or guidelines would be beneficial for patients with CHwI.

Objective:

Demonstrate the success of collaborative efforts between the specialized multidisciplinary Infusion Pharmacy Provider (IPP), the prescriber, patient and payer, in achieving improved outcomes.

Methods:

A Case Study including chart review, cost analysis, and interviews with patient and prescriber.

Summary:

Patient is a 23-year-old male with severe hemophilia A and an inhibitor, followed by a Hemophilia Treatment Center (HTC). Patient developed a high titer inhibitor with a Bethesda Titre of 1000 BU/ml as a child. Several complex treatment plans including: Immune Tolerance Therapy (ITT) utilizing plasma derived and recombinant factor products, immunosuppressive therapy, and prophylaxis with bypassing agents failed. Complications with implanted ports resulted in hospitalizations and replacement of approximately twenty ports. Numerous hospitalizations for uncontrolled bleeding episodes and pain management contributed to a disruptive childhood/adolescence and suboptimal quality of life for the patient and family.

Patient was unable to attend school regularly, develop socially, or participate in normal age-appropriate activities. Repeated uncontrollable bleeding episodes led to the development of target joints and hemarthrosis. The complex nature of the patient’s treatment regimen, his psychosocial issues, bleed history, and cost of therapy resulted in frequent communication and collaboration between all stakeholders to maximize therapy outcomes.

Inhibitors presents a significant management challenge.2 Emicizumab (Hemlibra®) was approved for the treatment of hemophilia A with inhibitors in November 2017. Well in advance of the transition, the IPP and prescriber discussed the benefits with the patient. Although understandably reluctant due to his history of failed therapies, the patient agreed to try Emicizumab. Initial doses were administered at the IPP’s Alternate Infusion Suite (AIS) under clinical observation, per prescriber’s request. The patient and caregiver received extensive education regarding potential adverse events, self- administration, and bleed treatment regimen during these visits.

Conclusion:

The coordination of care, communication, and goal alignment by all stakeholders resulted in positive outcomes for this patient. Following eighteen months of therapy with Emicizumab, the patient reports improved over-all quality of life as evidenced by his ability to maintain employment, attend college, and engage in social events/ activities. Twenty-two hospitalizations in the twelve months prior to changing therapies decreased to one in the eighteen months after transitioning. His bleeding events decreased from six to eight bleeds per month to one bleed in the past eighteen months and this bleed was attributed to a missed dose. Education on the importance of adhering to prescribed dosing schedule was reinforced by both the IPP and HTC. His port has been removed. Along with his significant increase in quality of life, the dramatic decrease in overall cost of care will be highlighted.

Objective:

The adolescent/adult pivotal phase 3 pathfinder 2 trial assessed N8-GP (turoctocog alfa pegol, ESPEROCT^®) use for routine prophylaxis and treatment of bleeds in previously treated patients (PTPs).

Methods:

pathfinder 2 was a multi-center, multi-national, single-arm study evaluating safety, efficacy and pharmacokinetics. Adolescents/adults (aged ≥12 y) with severe hemophilia A were administered prophylaxis (50 IU/kg Q4D) in the main phase with option for eligible patients (0-2 bleeds in prior 6 months) to randomize (2:1) to 75 IU/kg Q7D or 50 IU/kg Q4D during extension 1 (24 weeks) and continue treatment into extension 2. An on-demand group was included throughout. Current analysis covers January 2012 through December 2018.

Summary:

Of the 186 PTPs (including 46 [25%] from the US) enrolled in the main phase, 150 (81%) started extension 1, 139 (75%) completed extension 1, and 128 (69%) completed the study. Mean age was 31.1 years, weight 75 kg and BMI 24.3.

The complete trial covers 785 patient-years of treatment (66,577 exposure days [ED]) during which there were 2,758 bleeds, including 1,807 (66%) spontaneous bleeds and 1,735 (63%) joint bleeds. Twelve patients treated on-demand for a mean 3.1 years reported nearly half of all bleeds (1,270, 46%), including 971 (54%) spontaneous bleeds and 627 (36%) joint bleeds. Hemostatic efficacy was rated excellent/good in 2,470 (90%) episodes; 2,614 bleeds (95%) were treated with 1-2 injections.

Of 175 patients on prophylaxis, 55 of 110 eligible were randomized in extension 1. For 177 patients treated with 50 IU/kg Q4D prophylaxis for 613 years (57,723 ED), 126 (71%) experienced 1,312 bleeds. For 61 low-bleed patients with 134 years (7,255 ED) on 75 IU/kg Q7D prophylaxis, 53 (87%) experienced 176 bleeds. Median ABRs are shown in the TABLE.

N8-GP mean trough levels were 3.1 IU/dL on 50 IU/kg Q4D and 1.0 IU/dL on 75 IU/kg Q7D.

A total of 1,827 adverse events were reported over 785 exposure years, including 63 serious adverse events. One patient with an intron 22 inversion developed a low-titer inhibitor at 93 ED and was withdrawn when it progressed to >5 BU. Non-neutralizing anti-PEG antibodies were seen at baseline in 12 patients (6.5%) prior to first N8-GP exposure and 11 (5.9%), who had negative anti-PEG at baseline, had positive antibodies after exposure.

Conclusion:

These data support the safety and efficacy of N8-GP in a controlled phase 3 trial setting in adolescents/adults. Prophylaxis with N8-GP with a consistent dose/interval (50 IU/kg Q4D) was effective in preventing bleeds; extended dosing was evaluated as successful for a subgroup of low-bleed patients. No significant safety issues were identified. 

Objective:

The ongoing pediatric phase 3 paradigm 5 trial is assessing N9-GP (nonacog beta pegol, REBINYN^®) use for routine prophylaxis and treatment of breakthrough bleeds in previously treated children with hemophilia B (FIX ≤2%). This analysis presents 5-year safety and efficacy data in a group of children treated with weekly prophylaxis to a higher mean FIX trough (≥15%).

Methods:

paradigm 5 is a multinational, single-arm study evaluating safety, efficacy, and pharmacokinetics. Children (aged ≤12 years at enrollment) were administered weekly prophylaxis (N9-GP 40 IU/kg) through a 52-week main phase followed by an ongoing extension study. Mild/moderate bleeds were treated with 40 IU/kg. Prophylaxis, bleed treatments, and hemostatic efficacy were captured in electronic diaries. Current analysis extends from May 2012 through October 2018.

Summary:

Of the 25 children enrolled in the main phase (12 ages 0-6, 13 ages 7-12), 24 completed the main phase and 22 entered the extension (11 per age group). At the time of this analysis, 17 remain in the trial. No patients withdrew due to adverse events. Ten participants remaining in the trial have become adolescents (mean 2.6 adolescent-years of exposure).

The cumulative exposure in the study was 116 patient-years (6,194 exposure days). The median (range) time in study was 5.2 (0.2-6.1) years representing 290 (10-325) N9-GP doses per patient. The median/mean prophylactic dose was 43.1 IU/kg/wk.

A total of 573 adverse events were reported, including 4 serious adverse events, all of which were considered unlikely related by the investigator. No patients developed anti-FIX inhibitory antibodies (primary endpoint). There were 7 medical events of interest, including 6 allergic reactions (no anaphylaxis).

Age-related increase in trough FIX levels was seen; the mean FIX trough levels were 0.179 IU/mL (overall), 0.166 IU/mL (younger), and 0.192 IU/mL (older). Mean PEG plasma concentration reached steady state after ~6 months.

Overall, 20 patients (80.0%) experienced 115 bleeds, the majority of which were traumatic (64%) or spontaneous (33%) and in joints (43%). Most (93%) were treated with 1-2 doses with 89% rated as excellent/good. Median individual ABRs are shown in the TABLE; 64% of patients were spontaneous-bleed-free throughout the study.

Conclusion:

These data support the safety and efficacy of N9-GP 40 IU/kg weekly over a median of 5 years in a controlled phase 3 trial setting in children. N9-GP prophylaxis with a trough of ~18% was effective in preventing bleeds with low reported ABR and with 64% of patients reporting no spontaneous bleeds during the entire study period. No unexpected safety issues were identified.

Objective:

Daily administrations of FVIII products are considered useful for providing high FVIII coverage for active patients with hemophilia A. This analysis was performed to determine the daily dose levels required of N8-GP (turoctocog alfa pegol, ESPEROCT^®) vs standard half-life (SHL) FVIII (N8, turoctocog alfa, Novoeight^®) to normalize risk of activity-related bleeding for patients with hemophilia participating in daily sports activities (practices, games) of varying risk profiles.

Methods:

Patients with hemophilia engaging in physical activity have associated increased bleeding risk with sports that have increased potential for contact injuries as classified by Broderick et al (JAMA. 2012): Class 1 - no contact (eg, swimming); Class 2 - contact might occur (eg, basketball); and Class 3 - inevitable contact (eg, American football). To normalize the risk of bleeding, nominal targets of FVIII activity levels for at least 2 h/d based on Broderick et al were chosen: above 30% (Class 1), above 50% (Class 2), and above 70% (Class 3).

Pharmacokinetic (PK) simulations were performed using a one-compartment model with first-order elimination. FVIII PK profiles were simulated for the extended half-life (EHL) N8-GP based on the pathfinder 1 PK trial showing 60% prolonged half-life compared with prior SHL FVIII. For PK simulations of an SHL, N8 was used due to 104⁰F stability with PK based on the guardian clinical trial program.

Summary:

Daily doses to sustain at least 2 h/d of 30%/50%/70% activity were estimated for N8-GP (9, 15, and 21 IU/kg) and N8 (14, 23, and 33 IU/kg). Steady-state PK profile simulations of once-daily administration are shown in the Figure.
 

Conclusion:

Experience with routine prophylaxis with EHL/SHL FVIIIs towards guideline recommended >1% activity does not readily translate to HCP understanding of the PK with high daily or much higher every-other-day administration required to minimize risk for the active patient. With a 1.6x (60%) prolongation in half-life for adolescents/adults, this model shows daily N8-GP to be a more efficient strategy compared with daily SHL FVIII (N8) to cover the active patient; N8-GP achieves higher trough levels with a smaller increase in overall factor consumption compared with standard prophylaxis with SHL FVIII. 

Objective:

The completed pediatric phase 3 pathfinder 5 trial assessed the safety and efficacy of N8-GP (turoctocog alfa pegol, ESPEROCT^®) use for routine prophylaxis and treatment of breakthrough bleeds in previously treated children.

Methods:

pathfinder 5 was a multicenter, multinational, single-arm study evaluating safety, efficacy, and pharmacokinetics. Children (aged <12) with severe hemophilia A were administered prophylaxis (target 60 [50-75] IU/kg twice weekly) in the main phase (26 weeks) followed by an extension phase. Current analysis covers study initiation (February 2013) through completion (September 2018).

Summary:

Of the 68 children (34 aged 0-5, 34 aged 6-11) enrolled, 63 completed the main phase and 62 completed the extension. Most (95%) were previously on prophylaxis. The total study period amounted to 306 patient-years (32,138 exposure days); median (mean) patient exposure was 4.9 (4.5) years.

Overall, 838 adverse events (AEs) were reported; 18 serious AEs included 2 possibly/probably related to N8-GP (severe allergic reaction [1] and increasing bleeding symptoms [1]). No inhibitor development was observed in the trial. Two AEs resulted in withdrawal; a third patient with severe allergic reactions (after 4 doses) that resolved after 2 hours without any treatment met preestablished withdrawal criteria. There were no anti-PEG antibodies of clinical significance; however, 21 (31%) patients had anti-PEG antibodies at baseline (prior to exposure), and 1 patient had a single positive measurement after exposure at a titer <1.

Overall, 55 patients (81%) reported 330 bleeds during the study; most were traumatic (67%). The success rate for hemostasis was 84% (excellent/good); 71% were treated with 1 injection, and 88% of patients were successfully treated with 1-2 injections. Median (mean) utilization for bleeds was 68 (95) IU/kg.

Median ABRs are shown below; estimated mean ABR was 1.1. Forty-seven percent of children had no spontaneous bleeds throughout the trial. Of 13 children with 17 target joints at baseline, 77% (main phase) and 46% (complete trial) reported no bleeds in their target joints. For those previously on prophylaxis, the mean observed ABR was 2.3 compared with the historical ABR of 6.4. The mean prophylaxis dose was 64.7 IU/kg with an interval of 3.5 days.

N8-GP prolonged single dose half-life by 1.9x compared with the child’s prior FVIII product. The mean trough levels on twice-weekly dosing were 0.019 IU/mL (0.016 ages 0-5, 0.024 ages 6-11).

Conclusion:

These data support the safety and efficacy of N8-GP in a controlled phase 3 trial setting in children. Prophylaxis with N8-GP using a consistent dose/interval (65 IU/kg twice weekly) was effective in preventing bleeds. No unexpected safety issues were identified. 

Objective:

Hemophilia A (HA) is an X-linked disorder caused by mutations in the gene encoding Factor VIII protein (FVIII). Gene therapy is increasingly being viewed as a viable treatment option for hemophilia. Herein, long-term clinical safety and efficacy are presented from a Phase 1/2 study of an AAV-mediated gene therapy for severe HA.  
 
Methods:

Valoctocogene roxaparvovec is an adeno-associated virus-mediated gene therapy that delivers a functional, codon-optimized, B domain-deleted, human FVIII gene under the control of a liver-specific promoter (AAV5-hFVIII-SQ). An ongoing Phase 1/2 study continues to evaluate the safety and efficacy of valoctocogene roxaparvovec in thirteen males with severe HA. Study participants received a single intravenous injection of valoctocogene roxaparvovec at one of two dose levels (6×10¹³vg/kg, n=7; 4×10¹³vg/kg, n=6).

Summary:

Participants who received 6×10¹³vg/kg valoctocogene roxaparvovec showed a reduction in annualized bleeding rate (ABR) of 96%, from a pre-treatment median(mean) of 16.5(16.3) to 0.0(0.7) at year three. Participants demonstrated an absence of target joints and target joint bleeds, with 86% experiencing zero bleeds requiring FVIII treatment. ABR diminished by 92% in 4×10¹³vg/kg participants, from a pre-treatment median(mean) of 8(12.2) to 0(1.2) at year two. Sixty-seven percent of 4×10¹³vg/kg participants experienced zero bleeds requiring FVIII treatment.
 
FVIII usage demonstrated a reduction from pre-treatment median(mean) of 139(137) infusions to 0(5.5) at year three in 6×10¹³vg/kg participants, and from 156(147) to 0.5(6.8) at year two in 4×10¹³vg/kg participants.
 
In 6×10¹³vg/kg participants, FVIII levels reported by chromogenic assay reached a median(mean) of 60.3(64.3), 26.2(36.4), and 19.9(32.7) IU/dL at the end of one, two, and three years post-infusion, respectively. In 4×10¹³vg/kg participants, FVIII levels reported by chromogenic assay reached a median(mean) of 22.9(21.0) IU/dL and 13.1(14.7) IU/dL at the end of one and two years post-infusion, respectively. Although FVIII levels were measured and will be presented using both the chromogenic substrate assay and the one-stage assay, chromogenic assay results appear to more accurately represent the true level of circulating FVIII.

The safety profile of valoctocogene roxaparvovec remains favorable and unchanged, with transient, asymptomatic ALT elevations and no FVIII inhibitor development reported to-date.

Conclusions:

Following a single administration of valoctocogene roxaparvovec, participants showed sustained, clinically relevant FVIII activity that reduced self-reported bleeding and exogenous FVIII replacement use at 156 weeks and 104 weeks post-administration in 6×10¹³vg/kg and 4×10¹³vg/kg dose cohorts, respectively.

Objective:

Inhibitor development is the most serious complication of hemophilia A therapy. Immune tolerance induction (ITI) is the gold standard for inhibitor eradication, restoring factor VIII (FVIII) responsiveness. Retrospective data on ITI therapy using rFVIIIFc have been reported (Carcao et al. Haemophilia. 2018). The ReITIrate study (NCT03103542) was designed to prospectively evaluate success of rescue ITI with rFVIIIFc.

Methods:

ReITIrate, a prospective, interventional, multicenter, open-label study, enrolled patients with severe hemophilia A and inhibitors, who failed previous ITI attempts. The primary purpose is to describe the outcome of ITI performed with rFVIIIFc (200 IU/kg/day) within a maximum of 60 weeks. Here, patient baseline characteristics are reported using descriptive statistics and listings.

Summary:

Sixteen subjects were included in the study between November 2017 and December 2018. The median (range) age at study enrollment was 7.5 (2–46) years. Seven subjects had a known family history of inhibitors. The median (range) number of prior ITI attempts was 1 (1–3) and the median (range) total ITI duration was 51.5 (12–155) months. All subjects had previously received high-dose ITI, with 3 subjects receiving plasma products, 6 subjects receiving recombinant products, and 7 subjects receiving both recombinant and plasma products for previous courses of ITI. Four subjects received prior immunomodulatory therapy. The median (range) inhibitor titer at screening and historical peak were 11 (0.9–635) BU/mL and 127 (8–3000) BU/mL, respectively. During the 12 months prior to enrollment, the median (range) number of bleeds was 5 (0–24); 11 subjects used activated prothrombin complex concentrate (aPCC) for treatment of bleeds, 5 subjects received recombinant factor VIIa (rFVIIa), and 1 subject each received FVIII/von Willebrand factor, recombinant FVIII, and tranexamic acid. Twelve subjects received prophylaxis with bypassing agents during this period (10 aPCC, 1 rFVIIa, and 1 both products).

Conclusions:

This is the first prospective study describing rescue ITI with an extended half-life recombinant FVIII product. Enrolled subjects had multiple risk factors for poor ITI outcomes and a long duration of previous ITI. There is an unmet need for successful tolerization in such patients, allowing regular FVIII prophylaxis and potentially leading to improved clinical outcomes and quality of life.

Objectives:

This study has a primary objective to determine the efficacy of VWF/FVIIII concentrate (Wilate) in the prophylactic treatment of previously treated patients with type 3, type 2 (except 2N), or severe type 1 VWD.

Secondary objectives of this study will be to collect data to 1) Assess the VWF:Ac and VWF:Ag incremental IVR of VWF/FVIIII concentrate over time, 2) Assess the safety and tolerability of VWF/FVIIII concentrate in this indication.

Also the study will examine, the efficacy of VWF/FVIIII concentrate in the treatment of breakthrough bleeding episodes (BEs), and in surgical prophylaxis, as well as the quality of life (QoL) during prophylaxis with VWF/FVIIII concentrate.

Methods:

The study is planned to enrol 28 PTPs aged ≥6 years and with VWD type 1, 2A, 2B, 2M, or 3. Eligible patients must be receiving on-demand treatment with a VWF-containing product, with at least 1, and an average of ≥2, documented spontaneous BEs per month in the preceding 6 months requiring treatment with a VWF-containing product. This will be assessed as part of a run in observational study to collect bleeding rate prior to the start of prophylaxis.

From the beginning of the study, patients will receive prophylactic treatment with VWF/FVIIII concentrate for 12 months and record all BEs in a patient diary. Based on these data, the frequency of BEs and the annualized bleeding rate (ABR) under prophylactic treatment will be calculated.

Treatment efficacy of BEs will be assessed by the patient (together with the investigator in case of on-site treatment) using a 4-point scale (excellent, good, moderate, none)
In case patients undergo surgeries, efficacy of VWF/FVIIII concentrate will be assessed at the end of surgery by the surgeon and at the end of the postoperative period by the haematologist. In both cases, predefined assessment criteria will be used. In addition, an overall assessment of efficacy will be made at the end of the postoperative period by the investigator.

Summary/conclusions:

Prophylactic treatment in other congenital bleeding disorders is widely accepted as the standard of care to prevent bleeding and preserve quality of life in patients. This form of treatment in VWD is not well characterized prospectively as yet. This study will provide data on the efficacy of prophylactic treatment in reducing the rate of bleeding and on the impact of prophylaxis on the quality of life in VWD patients.
 

Background:

Recombinant adeno-associated viruses (rAAV) are replication-deficient, non-integrating viruses commonly used as vectors for gene therapies currently in clinical development. Systemic administration of gene therapy raises the possibility of vertical germline transmission of the vector DNA.

Aim:

Here, we investigated the possibility of germline transmission following IV administration of an AAV serotype 5 vector designed for the liver-directed expression of human Factor IX which is being studied in clinical trials for hemophilia B.

Methods:

Since hemophilia B predominantly occurs in male patients, paternal germline transmission was investigated in mice in a GLP compliant study, according to current gene therapy guidelines (EMEA/273974/2005). Male C57Bl/6 mice (n=15) each received a single intravenous infusion of 2x1014 gc/kg AAV5-hFIX and were mated 6 days later with untreated female mice (n=30). On day 20 post-treatment, males were sacrificed and the seminal vesicle, epididymis, testes and a sperm sample were collected. Successfully mated females were necropsied on day 17 of gestation and the uterus, placenta and fetuses collected for each female. Each fetus was examined for viability and externally visible abnormalities. All samples were analyzed for vector DNA by QPCR.

Results:

No effect of treatment was observed on male mating performance, fertility indices, maternal body weight, food consumption, pregnancy performance, external fetal abnormalities, or fetal weights. Vector DNA levels of up to 2x106 gc/μg gDNA were detected in male reproductive tissues (epididymis, seminal vesicle, sperm, and testes), but not in female uterus, placenta and offspring. Although vector DNA was detected in the reproductive tissues of males, there was no evidence of transmission of vector DNA to female reproductive tissues or to the fetuses.

Conclusion:

The risk of paternal germline transmission following AAV5-based vector administration is therefore considered to be low.

Objective:

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, however, initial diagnosis and subsequent management of patients after diagnosis remains a challenge. The aim of this study was to characterize the specialists who are treating patients before and after diagnosis of VWD. We also identified the most common bleeding types and the treatments given to these patients.

Methods:

This retrospective study analysed data from a US medical claims insurance database (IQVIA PharMetrics Plus Database) for patients who had made insurance claims for VWD (International Classification of Diseases, ninth edition [ICD-9] code: 286.4). The claims were made from January 01, 2006 to June 30, 2015. Patients with ≥2 medical claims for VWD and who were continuously enrolled for a 2-year period before and after their 1 st VWD claim were included in this study. Descriptive statistics were used to summarize patient demographic and clinical characteristics, which included bleed types, treating physician specialty, and type of VWD treatment, in both the pre- and post-diagnosis periods.

Summary:

A total of 3,756 patients were included: 73% were female, and the median age at VWD diagnosis was 34 years old (age range 2–82 years). Pre-diagnosis, the top 3 treating physician specialties were hospitalists (22%), primary care physicians (14%) and obstetrician-gynecologists (13%). Post-diagnosis, the top 3 treating physician specialties were hospitalists (14%), primary care physicians (8%) and obstetrician- gynecologists (10%). Only 6% of patients saw a specialist hematologist before VWD diagnosis for a bleeding event and this decreased to 3% after diagnosis. The number of claims made by patients for bleeding events decreased from 45% pre-diagnosis to 34% post-diagnosis. In females, heavy menses were the most common bleed type, representing 29% of pre-diagnosis claims and 21% of post-diagnosis claims. In males, epistaxis was the most common bleed type, representing 13% of pre-diagnosis claims and 8% of all post-diagnosis claims. Overall, insurance claims for medical treatments associated with VWD increased from 19% pre-diagnosis to 27% post-diagnosis. The most prescribed treatments in women were oral contraceptives, desmopressin (DDAVP) and aminocaproic acid (ACA) (pre-diagnosis: 18%, 5% and 2%, respectively; post- diagnosis: 20%, 11% and 5%, respectively). In men, the most prescribed treatments were DDAVP, ACA and von Willebrand factor (VWF) concentrates (pre-diagnosis: 5%, 4% and 2%, respectively; post-diagnosis: 9%, 6% and 4%, respectively).

Conclusions:

These data show an overall reduction in the frequency of bleeding event insurance claims after VWD diagnosis. This was coupled with an increase in treatment insurance claims for DDAVP, ACA and VWF after diagnosis. These results highlight the importance of diagnosis of VWD and treatment optimization in these patients. Also, only a minority of patients received care from a hematologist, which may impact treatment and care.

Factor XIII deficiency is classified under rare bleeding disorders and is in fact, the rarest with an incidence of 1 in 2 to 3 million births and is inherited in an autosomal recessive manner. On the other hand, Von Willebrand Disease (VWD) is the most common bleeding disorder occurring in about 1% of the US population. Type 2M Von Willebrand Disease (Type 2M VWD), a subtype of Type 2 VWD, has an autosomal dominant pattern of inheritance and is characterized by decreased activity of Von Willebrand Factor (VWF) and its failure to interact with platelets. This report describes an interesting case of an individual with a combined severe congenital factor XIII deficiency and a recently diagnosed Type 2M VWD.

A 43 year old male diagnosed with severe congenital factor XIII deficiency at birth following umbilical stump bleeding has been on regular prophylaxis since 2007. Frequent breakthrough bleeds despite receiving prophylactic infusions of Factor XIII concentrate prompted a re-evaluation of the patient’s coagulation profile. Clinical laboratory parameters consistent with a diagnosis of Type 2M VWD were observed in addition to his underlying severe Factor XIII deficiency. DNA sequencing identified a novel missense variant p.Arg1136Trp (c.3406C>T) as the possible causative mutation.

Weekly blood draws overlapping 3 cycles of prophylactic infusions of Tretten (recombinant FXIII-A subunit concentrate) revealed peak and trough factor XIII activity levels of ~80% and ~10% respectively. The subject had a largely sedentary life style over this period of 12 weeks indicating, based on previous experience, that any moderate to vigorous physical activity could necessitate maintenance of a higher trough level. Additionally, the potential utility of VWF concentrates to effectively manage the second hemostatic defect and prevent breakthrough bleeds needs to be explored.

To our knowledge, this is the first report describing a unique combination of severe congenital factor XIII deficiency and type 2M VWD.

Objective:

We conducted a pilot study using a single open-ended question to elicit patient-perceived challenges and management strategies in individuals with bleeding disorders. The de-identified responses and themes expressed in this study were analyzed. The identification of perceived challenges and management strategies in individuals with bleeding disorders offers the opportunity to improve value based care.

Methods:

This retrospective, cross-sectional cohort study used a sample of convenience at The Hemophilia Center at OHSU. Study population included 20 participants. Inclusion criteria included: ages seven to eighty nine, diagnosed with a bleeding disorder and seen during any outpatient Hemophilia Center clinic visit between March 1, 2017 and April 30, 2018. Participants were included if, during the course of their clinical care, they answered the question, “What is the most significant (or greatest) challenge you have in managing your bleeding disorder and what do you do about it?” Data extracted included question response, age, type and severity of bleeding disorder. Responses were analyzed for themes by the investigators and using qualitative data analysis software. Coded demographic data was correlated.

Summary:

Seven challenge themes were identified: activity restrictions, infusions, emotion/stress, pain, future plans, education and access. Management themes included: self-advocacy, parent directed, activity modification or avoidance, acceptance, inquiry, asking for assistance, planning ahead, resiliency, and peer supports. Younger participants’ (9-17 years) challenges included activity restriction and infusions with management strategies of self-advocacy, activity avoidance and modification. Participants aged 18-57 years highlighted challenges with access to care, infusions, emotion/stress, pain, education and future planning. Management strategies in this group were focused on acceptance, planning ahead, peer support and resiliency. Analysis based on severity of bleeding disorder revealed that subjects with severe hemophilia reported infusions and activity restriction as their most significant challenge, with self-advocacy and activity modification management strategies. Participants with moderate hemophilia reported challenges centered on activity restriction and education of peers, with management strategies being self-advocacy and planning ahead. There were no differences in themes identified when analyzed based on type of bleeding disorder.

Conclusions:

This study characterizes the unique challenges and management strategies described by individuals with bleeding disorders. The themes highlighted the importance of patient voice and can be used to inform individual care decisions.

Introduction and Objectives:

Von Willebrand disease (VWD) is the most common bleeding disorder, affecting men and women equally. Despite this, awareness surrounding VWD is low. Outreach efforts often only target women, leaving many to assume VWD does not affect men. To begin changing this perception, the National Hemophilia Foundation (NHF) conducted a needs assessment to understand men’s awareness of VWD and experience getting a diagnosis for future programming.

Materials and Methods:

On behalf of NHF, The Harris Poll conducted a nationally representative online survey. From 2015 to 2016 1,002 adult men in the US were interviewed to learn about their health behaviors and awareness of VWD. A second online survey was conducted by NHF targeting men who were diagnosed with VWD to learn about their path to diagnosis and the impact of VWD on their lives. This survey was given to adult men in the US from 2016 to 2017 and 49 responses were included in the analysis.

Results:

The Harris Poll found that only 28% of men say they are aware of VWD and 68% are not sure of the symptoms. Medical providers (69%) are the main sources the men turned to for information about their health, followed by internet sources (40%). The second survey found an average of 8 years from first symptoms to final diagnosis, with almost 60% of respondents diagnosed at 18 years of age and older. When asked what motivated them to seek medical care, 45% cited a significant bleeding incident. Over half reported limitations to work, physical and social activity. Medical providers were one of the most common sources of information and support for men with VWD and the first place men went for information.

Conclusion:

More awareness of VWD is needed and outreach focused online and to medical providers. Diagnosed men need more education and support surrounding their disorder. NHF will continue to pursue outreach efforts and creation of resources for men with VWD.

Background:

Inherited factor X deficiency is an autosomal recessive bleeding disorder with an estimated occurrence rate of 1:1,000,000¹. Historically, bleeding symptoms have been treated with topical therapies, antifibrinolytic agents, fresh frozen plasma (FFP) or plasma-derived FIX concentrates (PCCs). In 2015, the first factor X (FX) concentrate was approved in the U.S.

Objective:

This organization was interested in reviewing clinical outcomes such as perceived pain and unplanned hospitalizations of adults and children with FX disease currently being treated in the home with Coagadex®. METHODS: This organization conducted a retrospective review of a population of seven adult and pediatric patients. Patients were surveyed for pain, bleeding episodes, hospitalizations/ ER visits, dosing parameters and administration methods pre/post initiation of FX therapy. There were 3 children, 12 years old and under and four adults. Ages ranged from 5-60 years old with the average age of 27.9. There were five males and two females. The average length of treatment was 6.4 months. One patient was naïve, six converted from other therapies. Dose ranges administered by caregivers or self-infusion were 750 -2800 IU (26-61 IU/Kg). One patient was on-demand and six were administering prophylaxis therapy.

Results:

There were two converted prophylaxis patients reported pain with PCC’s and none with FX; one on-demand naïve patient stated his pain was markedly improved with prn administration of FX; four converted prophylaxis patients with no prior pain history reported no changes in pain on FX therapy. For on-demand patients treating bleeding episodes, three reported a decrease in the number of bleeding episodes, three were unchanged and one reported one additional bleeding episode. A total of ten hospitalizations or emergency room visits were reported during the six months prior to initiation of FX treatment and only one in the six months following initiation of treatment.

Conclusion:

Early recognition and home treatment with FX concentrate allows for prompt resolution of bleeding symptoms, decreased pain and decreased hospitalization or emergency room visits. Further investigation is needed to determine cost-savings for decreased hospitalization/ ER visits.References:Brown, D.L. & Kouides, P.A. (2008). Diagnosis and treatment of Inherited Factor X deficiency. Haemophilia. (14). 1176-1182. Retrieved from: https://www.hemophilia.org/sites/default/files/document/files/DiagnosisAndTreatmentOfInheritedFact…

Objective:

We sought to explore real-world outcomes, such as annualized bleeding rate (ABR) and markers of adherence, in persons with hemophilia A (PwHA) or with hemophilia B (PwHB) who receive standard half-life (SHL) or extended half-life (EHL) factor VIII (FVIII) or factor IX (FIX) replacement products.

Methods:

We analyzed de-identified data from the Adelphi Disease Specific Programme (DSP) database, a patient health record–based survey of hematologists in the US and 5 European countries (France, Germany, Italy, Spain and the UK). Data were collected from May–November 2017 for male patients with moderate or severe HA or HB. Outcomes in the two groups of patients (SHL vs EHL) were compared and descriptive statistics were used to summarize results.

Summary:

A sample of 595 patients with HA or HB met the inclusion criteria (US, n=123; Europe, n=472). Age, weight, and body mass index (BMI) were similar between SHL and EHL groups for PwHA and PwHB on both continents. Higher ABR was noted consistently in Europe vs the US. Hemophilia A: Analysis included 101 patients from the US (SHL, n=64; EHL, n=37) and 360 patients from Europe (SHL, n=340; EHL, n=20). The ABR was similar between both groups on both continents (median: US, 1.0 SHL and 1.0 EHL; Europe, 1.0 SHL and 1.5 EHL; mean: US, 1.3 SHL and 1.2 EHL, P=0.68; Europe, 1.8 SHL and 1.7 EHL, P=0.76). The mean of the physician-reported ‘number of doses missed of the last 10 doses’ appeared to be numerically higher in the EHL vs the SHL group in the US (mean: 0.4 SHL and 1.6 EHL, P=0.13), whereas in Europe, the trend was reversed (mean: 0.7 SHL and 0.0 EHL, P=0.29). Hemophilia B: Analysis included 22 patients from the US (10 SHL; 12 EHL) and 112 patients from Europe (91 SHL; 21 EHL). The median ABR for PwHA and PwHB in the US was 1.0 (SHL) and 1.0 (EHL), and the mean was 1.6 SHL and 0.8 EHL (P=0.25); in Europe, the median ABR was 2.0 SHL and 1.0 EHL, and the mean was 2.2 SHL and 1.6 EHL, P=0.25. The mean of the physician-reported ‘number of doses missed of the last 10 doses’ was 0.8 SHL and 0.5 EHL (P=0.63) in the US and 0.6 SHL and 0.1 EHL (P=0.33) in Europe.

Conclusions:

These preliminary real-world data, unadjusted for treatment regimen and inclusive of US and ex-US sampling, showed no clinically meaningful difference in ABR or adherence markers in PwHA or PwHB who received SHL versus EHL FVIII or FIX products. These observations may challenge assumptions regarding adherence and or clinical outcomes associated with SHL/EHL product selection among PwHA and PwHB. Further analyses should be explored.

Objective:

The Evolving Treatment of Hemophilia’s Impact on Neurodevelopment, Intelligence and Other Cognitive Functions (eTHINK) study aims to evaluate the impact of hemophilia on neurodevelopment and cognitive function through the use of validated instruments and to identify covariates that drive differences in neuropsychological performance.

Methods:

A sample of at least 510 males aged 1-21 years (~25 per age) with hemophilia A or B (any severity, with or without inhibitors) will be enrolled in a cross-sectional, non-interventional study. Following ethics review and informed consent, data collected will include a structured developmental and hemophilia history interview, a standardized neurologic examination, and a comprehensive neuropsychological assessment of cognitive/motor development (Bayley-III), intelligence (WPPSI-IV/WASI-II), attention/processing speed (CogState™), executive function (BRIEF-P/BRIEF2/BRIEF-A), mood and behavior (BASC-3), and adaptive behavior (ABAS-3). Assessments will include objective tests as well as parent and patient self-report rating scales. Z scores will be derived from published general population norms for each instrument and analyzed to develop hemophilia population specific norms. Secondary analysis for predictors of outcome will include regression modeling and chi-square tests of top vs bottom quartile responses.

Summary:

Initiated in the early 1990s under Centers for Disease Control, Maternal and Child Health Bureau, and National Institutes of Health, the Hemophilia Growth and Development Study (HGDS) evaluated the impact of hemophilia on neurodevelopment, executive function, and intelligence. The 4-year observational study enrolled 333 patients from 14 US centers, aged 6-18 years at baseline (62% HIV+), who underwent annual/semi-annual comprehensive assessments including neurologic examination, neuroimaging (MRI), and neuropsychological assessment. Results suggested that hemophilia and HIV had independent effects at baseline and follow-up. Baseline neurologic examination findings were common, as were progressive abnormalities of gait/coordination. Imaging showed baseline CNS bleeds in 12% of patients and new CNS bleeds (2% per year), which often occurred in the absence of reported head trauma. HIV+ children were more likely to show lower scores on neuropsychological assessments. Academic/adaptive skills were lower than expected based on mean IQ, and more behavioral/emotional problems were seen, including attention abnormalities related to known/silent CNS bleeds. There was a large shift in mean scores in IQ and achievement for the children with more severe hemophilia. Six small studies published between 1996 and 2009 reported impacts on academic achievement, attention, and behavior.

Conclusions:

HGDS established 25 years ago that hemophilia and HIV have independent effects on cognitive and behavioral function in children with hemophilia. Since then, standards of care in hemophilia treatment have changed significantly, but no follow-up studies have investigated whether these changes have affected the profile of neurocognitive outcomes in hemophilia. We therefore designed the eTHINK study to provide valuable insights into whether subgroups of children and young adults with hemophilia remain at risk for impaired neuropsychological outcomes.

Objective:

BAY 94-9027 is an extended–half-life recombinant factor VIII (FVIII) product. In the PROTECT VIII Kids trial, BAY 94-9027 was efficacious for the prevention and treatment of bleeding episodes in previously treated children with severe hemophilia A. We report interim long-term efficacy and safety data from the PROTECT VIII Kids extension study.

Methods:

In PROTECT VIII Kids, previously treated patients (PTPs) aged <12 years with severe hemophilia A received BAY 94-9027 prophylaxis twice weekly (25‒60 IU/kg), every 5 days (45‒60 IU/kg), or every 7 days (60 IU/kg). Patients completing ≥50 exposure days (EDs) and ≥6 months in the main study or a 12-week safety substudy (part 2) that enrolled PTPs aged <6 years could continue in the optional extension for an additional ≥50 EDs.

Summary:

Fifty-nine of 73 patients treated with BAY 94-9027 in PROTECT VIII Kids (main study or part 2) continued in the extension (median [range] age at enrollment in the main study, 5.0 [2–11] years). At data cutoff (January 2018), patients had a median (range) of 1456 (351–1665) days in the trial (main study or part 2 plus extension). Patients in the extension received prophylaxis twice weekly (n=20), every 5 days (n=20), every 7 days (n=8), or switched prophylaxis frequency during the extension (variable frequency; n=11). Median (range) dose/infusion was 52.1 (19–62) IU/kg. Median annualized bleeding rate (ABR) for total bleeds was 1.8 for all patients and 0.8, 1.1, 2.1, and 3.2 for those treated twice weekly, every 5 days, every 7 days, or with varying frequency, respectively. Median ABR for joint bleeds in all patients was 0.7. During the extension, 3 patients (5.1%) experienced treatment-related adverse events (AEs) classified as mild (n=1), moderate (n=1), or severe (n=1). One patient discontinued because of a serious AE that was not related to treatment. No confirmed FVIII inhibitors or anti-PEG antibodies were observed; no patients had sustained levels of detectable PEG in plasma.

Conclusions:

Long-term treatment (up to ~4.5 years) with BAY 94-9027 prophylaxis was efficacious and well tolerated in previously treated pediatric patients with severe hemophilia A.

Objective:

Patient satisfaction with healthcare services is a measure of patient centeredness, influences treatment adherence, and increasingly affects reimbursement. In 2018, the US Hemophilia Treatment Center Network (USHTCN) launched the second national Patient Satisfaction Survey (PSS).

Methods:

A Steering Committee and Regional HTC Coordinator work group updated, piloted, and finalized the two-page survey for patient self-administration online, at clinic, or at home, in English or Spanish, and mailed to households. Survey content and format were based on national health surveys to enhance comparability and scientific robustness. Questions included assessed patient demographics, satisfaction with team members, and care processes aligned with HRSA goals. An open ended question sought qualitative data. Respondents were anonymous but the HTC where they received care was identified. Participation was voluntary. Persons with genetic bleeding disorders who had HTC contact in 2017 were eligible. Since March 2018, HTCs sent surveys to approximately 31,650 households. Parents were asked to complete surveys for children under age 15. No reminders were sent. Data were entered and analyzed at a central site and aggregated at national, regional and HTC levels. Survey remains open through summer 2018.

Results:

4042 individuals (12.8%) from 125 (90%) of the 139 Centers in the USHTCN returned surveys by June 12, 2018. National analyses on 4042 surveys reveal that 93% - 98% were ‘always’ or ‘usually’ satisfied with HTC care processes: shared decision making (97%); care coordination (97%); obtaining understandable information (97%); getting timely services (95%); enough time with staff (97%); being treated respectfully (98%); and HTC Factor Program/Pharmacy (340b) (96%). 95% - 97% were ‘always’ or ‘usually’ satisfied with core HTC team members. 91% of 12-17 year olds were ‘always’ or ‘usually’ satisfied with HTC encouragement regarding becoming more independent, and 92% with how the HTC discussed caring for a bleeding disorder upon reaching adulthood. Insurance and language were ‘always’ or ‘usually’ a problem for 14% and 9% respectively. 31% of respondents were female and 10% Hispanic. 80% were Caucasian, 5% African-American, 4% Asian/Pacific Islander or Native Hawaiian, 4% Multiple races, and 7% did not respond. Over 60% had severe or moderate FVIII or FIX deficiency or VWD Type 3. Ages ranged from newborns to over 90 years: 37% under 18, 18% age 18 – 34, and 45% over age 35.

Conclusions:

Implementing a National Patient Satisfaction Survey for the USHTCN remains feasible, is supported by HTCs nationally, and provides valuable information. Satisfaction with HTC services including 340B pharmacy is high. Insurance and language pose problems for 9-14%. Future analyses will examine additional national data and regional variation, and identify trends from the first national PSS conducted in 2014.

Objective:

My Life, Our Future (MLOF) seeks to advance understanding of hemophilia by developing the MLOF Research Repository, a resource for use in scientific study. To strengthen the database and improve clinical care for females, MLOF expanded in 2016 to collect data and samples from potential and confirmed carriers.

Methods:

MLOF is a collaboration between the American Thrombosis and Hemostasis Network (ATHN) (educates HCPs, collects and protects genetic data, manages ATHNdataset, manages research review committee), Bloodworks Northwest (BWNW) (performs genetic testing and analysis, manages MLOF Research Repository), National Hemophilia Foundation (educates patients and the community), and Bioverativ (provides scientific collaboration and sponsorship). Patients enrolled in MLOF can contribute their de-identified clinical information and specimens (DNA, RNA, plasma and serum) to the MLOF Research Repository. The patients’ hemophilic genetic data (F8 or F9 variant) and specimens are stored at BWNW and their clinical data in the ATHNdataset. For carrier project participants, an ISTH Bleeding Assessment Tool score is determined, and for confirmed carriers factor levels are obtained and recorded in ATHN Clinical Manager. Upon enrollment of 5,000 participants, the MLOF Research Repository was opened to U.S-based investigators in February 2017. Investigators were encouraged to partner with a participating hemophilia treatment center (HTC) on projects for clinical translational support. An independent, international, multidisciplinary panel of experts was convened to review research proposals, evaluating project feasibility, scientific merit and potential contribution to the bleeding disorders community.

Summary:

To date, 97 HTCs are actively participating in MLOF and have enrolled 8,246 patients. Of those, 83% (6,857), including 723 confirmed carriers, have consented to research. The samples of 427 additional females consenting to research are pending evaluation; 1,643 females have participated in MLOF. The first MLOF Research Repository cycle received 9 Letters of Intent and 7 were chosen for full proposal review. The final selection of studies will be announced to the community in June 2017.

Conclusions:

Combining and analyzing genetic and clinical data via this database may allow researchers to solve unmet needs in patients with hemophilia, including understanding inhibitor development, bleeding severity or aiding in identifying new therapeutic targets. By considering molecular drivers of disease and genetic variability, this approach could lead to more individualized treatment through advancement of precision medicine. Global expansion of the MLOF Research Repository is planned for 2018. Carrier testing may help females manage their bleeding disorder and may aid in family planning. Related to research, females provide a unique control group for males with hemophilia on natural history, modifier genes inside and outside the coagulation system, and epigenetic factors affecting outcomes.

Objective:

To identify sociodemographic, clinical and treatment characteristics associated with the quality of life (QoL) of individuals with hemophilia B (HB) using longitudinal data in the HUGS Vb cohort.

Methods:

Between 2009-2012, 148 persons with HB were enrolled into HUGS Vb, a prospective cohort study examining individuals seen at ten federally supported U.S. hemophilia treatment centers (HTCs). Participants or parents of pediatric enrollees completed periodic surveys; data from 107 individuals with at least three follow-up surveys, clinician charts and dispensing records were included in the analyses. Data were analyzed at baseline and 6-month intervals across 2 years, yielding 5 time points. Periodic QoL assessments (SF-12 for adults and PedsQL for children), self-reported pain, employment and insurance status, time lost from work/school and treatment regimen were collected. Descriptive statistics and Spearman’s correlation coefficient test were used to examine the associations.

Summary:

Forty-six percent of the sample had severe HB; 50% were children (2-17 years). Among those with severe HB, 64% of children and 50% of adults treated prophylactically. 58% of adults were employed full-time. Individuals with mild hemophilia missed more work/school days due to disease-related issues (8 days) than those with moderate hemophilia (2 days) or severe hemophilia (3 days, P=0.03). QoL scores were similar over time among those using prophylactic and on-demand treatment for both adults and children. Median adult Mental Component Scores (MCS) and Physical Component Scores (PCS) measured at 5 time points ranged from 53.0 to 55.1 for MCS and 45.5 to 50.5 for PCS, with no significant changes observed over time. However, adults employed full-time had significantly higher median PCS at each time point than those working less than full-time (all Ps<0.05). Adults who reported pain had significantly lower median PCS than those who reported no pain/pain only when bleeding at each time point (all Ps<0.03). Median MCS remained similar between the two groups. Overall, we observed no longitudinal differences in children’s total PedsQL scores (range of median: 81.2-92.4) or in functioning subscales. However, among 18 children with QoL scores at both baseline and 24 months, missed school days were significantly correlated with decreased social functioning over time (rho=0.73, P<0.001). 8% of children who reported pain had consistently lower median total QoL scores than those reporting no pain/pain only when bleeding, despite having access to insurance and prophylactic treatment.

Conclusions:

Longitudinal data collected by HUGS Vb provide a valuable opportunity to examine the association of HB patient characteristics with measures of QoL in a multi-state sample. These data demonstrate that lower QoL was consistently associated over time with multiple factors, including absence from school, unemployment and pain. Continued analysis of this cohort will increase our understanding of the challenges faced by persons with HB.

Objectives:

To better understand what symptoms beyond bleeds are experienced, as well as the depth of impact of these symptoms and how they uniquely impact people living with hemophilia on a daily basis. Additionally, the study aims to better understand patients’ satisfaction with current treatments in addressing their hemophilia needs.

Design/Method:

An email invitation was sent to all U.S. members affiliated with hemophilia A of MyHemophiliaTeam, a social network of people diagnosed with or caring for someone with hemophilia. 54 members responded to a 24 question survey between April 19 and May 1, 2017.

Results:

Hemophilia had a significant negative impact on the day-to-day life of adults (72%) and children (52%). Pain was the most broadly and acutely experienced symptom: 60% of adults and 28% of caregivers felt that pain had a major impact on their lives and 33% of adults and 25% of caregivers considered mobility to be significantly impacted by hemophilia.

For adults, both pain and mobility limitations impacted sleep (71% and 45%, respectively), being able to perform chores (71% and 65%), and the ability to work (48% and 45%). For children, these conditions impacted school attendance (61% and 58%) and participation in high impact activities like running or playing soccer (56% and 75%).

Depression and anxiety were also common symptoms that impacted sleep across adults (71%, 61%) and children (60%, 55%). Adults most commonly reported feeling negative ones: stress (38%), fatigue (38%) and annoyance (35%).

81% of adults and 86% of caregivers were extremely or very satisfied with current treatment. However, needs beyond treating bleeds are currently not being met. Few felt their pain was adequately addressed by current therapies (74% of adults and 57% of children reported no relief). Mobility impairment issues were also not being adequately addressed. Time spent on treatment impacted people with hemophilia (39% of adults and 43% of children, respectively were not satisfied with the frequency of treatment).

Background:

While people with hemophilia are known to suffer from bleeding, numerous concomitant symptoms also burden these patients, including pain, mobility impairments, depression, and anxiety. These symptoms can have a significant impact on quality of life, limiting work and school attendance, causing social withdrawal, and encouraging inactivity. Additionally, available treatment options can sometimes fall short in treating the totality of hemophilia symptoms.

Conclusions:

People with hemophilia have many challenges beyond bleeds that are not currently being well addressed. This is particularly true for the pain experienced. As such, a more holistic approach to treating hemophilia beyond bleeds would be beneficial to patients living with hemophilia. Additionally, therapies that reduce the need and frequency for treatment could potentially lower the burden of disease.

Objective:

Pain and functional impairment resulting from joint disease in patients with hemophilia (PWH) may impact emotional well-being, resulting in consistent reports of anxiety/depression. The P-FiQ study formally evaluated patient-reported anxiety/depression symptoms and treatment as well as responses to standardized patient-reported outcomes (PROs), and evaluated reliability, validity, and consistency of responses.

Methods:

At a comprehensive care visit, adult male PWH with a history of joint bleeding or pain completed a hemophilia history and 3 patient-reported outcomes (PROs) assessing anxiety/depression and quality of life (QoL): EQ-5D-5L, Brief Pain Inventory (BPI), and SF-36v2. PROs were assessed for reliability, consistency, and correlation with factors including patient-reported characteristics.

Summary:

A total of 381 PWH (median age, 34 years) were enrolled in P-FiQ; 77% had hemophilia A, 23% had hemophilia B, and 9% had inhibitors. Fewer than half (44%) were currently receiving routine infusions to prevent bleeding. More than half were employed full-time (53%), and 65% were married or had a long-term partner. Depression was reported by 19% and anxiety by 14%. On the EQ-5D-5L anxiety/depression item, 43% reported feeling anxious or depressed “today.” On BPI, most participants indicated that pain interfered in the previous week with mood, sleep, and enjoyment of life, and more than half (54%) indicated interference with relations with other people. On SF-36v2 (range 0- 100, higher scores indicate better QoL), median mental health summary score was 50.7; subdomains were similar (vitality, 49.0; social functioning, 45.6; role emotional, 55.9; mental health, 52.8). Emotional problems resulted in reduced time spent on work/activities (40%) and accomplishing less than they would like (47%). More than half (55%) had felt downhearted or depressed, and a large majority (93%) had felt tired in the past 4 weeks. Sixty percent of participants indicated that their physical or emotional problems had interfered with their normal social activities with family, friends, and other contacts. Similar items across PROs correlated with one another, and PRO scores (EQ-5D-5L anxiety/depression, SF-36 mental health) were significantly (P<0.05) correlated with self-reported anxiety/depression.

Conclusion:

Anxiety and depression in adults with hemophilia have been consistently reported in other studies and were identified in P-FiQ by self-report and across several PRO instruments. Emotional problems were reported to interfere with normal social activities and productivity. While the unmet need to address mental health in PWH has received increased recognition, it is not typically assessed formally. When compared with pain, management strategies and/or referral relationships may also not be as formally established. The findings presented here highlight the potential value of simple screening tools (eg, EQ-5D-5L) and opportunities to encourage patient dialogue about mental health within the comprehensive care setting and in referral networks.

Objective:

The B-HERO-S study assessed the impact of hemophilia on US adults with hemophilia B, including affected females. Here we describe the symptoms, management, and impact on education, employment, and engagement in recreational activities in women.

Methods:

Adults aged ≥18 years with hemophilia B (factor IX <40%) completed a survey including questions about bleeding, treatment, and psychosocial impact.

Summary:

Of 299 respondents, 86 were women (median age, 29 years; 6% were aged >45 years) with mild (29%), moderate (65%), or severe (6%) hemophilia. The majority reported arthritis (66%) and anxiety/depression (57%); 19% reported acute and/or chronic pain. Most (86%) were treated with some form of “routine infusions to prevent bleeding”; 16% reported self-infusing, 31%/17% by partners/family. Self-infusion was initiated at median age of 18, and learned from HTCs (86%), camps (71%), or parents (57%). Most reported difficulty with access to factor due to affordability/availability in the past 5 years (72%) or expected in the next 5 years (85%). Women reported a median (mean) of 4 (3.86) bleeds in prior year; 83% bled within the last 4 weeks with most recent bleeding in joints (73%) or muscles (21%). Twenty-five percent reported one specific “bad” joint, most commonly the knee (69%). Nearly all were seen in HTCs (85%) with a median (mean) of 3 (3.5) HTC visits per year. Most (88%) went past high school with 55% completing 4-year college and 24% graduate degrees. Most (94%) reported some negative impact on completing their education (7% very large/69% moderate/19% small impact), most commonly due to difficulties concentrating at school due to bleeds or pain (81%). Most were employed full-time (71%) or part-time (10%), commonly in office work (71%). Most (94%) reported a negative impact on their working life (3% very large/71% moderate/20% small impact); 36% reported leaving a job because of their hemophilia. Nearly all (99%) indicated some negative impact on their ability to engage in recreational activities (3% large/83% moderate/13% small impact). From a list of predetermined activities, dancing (50%) and walking (48%) were the most common current activities; bicycling (20%), dancing (17%), and swimming (16%) were the most common discontinued activities. Most reported treatment changes around activities (21% started prophylaxis, 52% revised time of doses, 38% added doses, 34% changed amount of doses); 8% reported no change and 3% no moderate/vigorous activities.

Conclusion:

Clinical presentation and treatment in women mirrored that reported by men except for greater anxiety/depression and more issues with access to treatment. Nearly all affected women reported a negative impact on their education, employment, and activities. While these results may be limited by bias in recruitment selecting those most symptomatic, the data reveal opportunities to improve awareness of and guidance around management and counselling of affected women.

Objective:

The B-HERO-S study evaluated the impact of mild-severe hemophilia B on the lives of affected adults and children. Here we assess the impact of hemophilia B on relationships.

Methods:

US adults with hemophilia B and caregivers of affected children completed separate 1-hour online surveys that included questions regarding impact on interpersonal relationships.

Summary:

Most (88%) of the 299 adults completing the survey had mild-moderate hemophilia B. Of those, 54% were married or in a long-term relationship, and 44% were single. Most adults (87%) reported that hemophilia impacted their ability to form close relationships with partners or prospective partners; 35% were very/quite dissatisfied with the support received from a previous partner. Ninety percent reported that their experiences in a prior relationship, including satisfaction with support from their previous partner, impacted their decision to enter a relationship with their current partner. Nearly all participants (98%) were very/quite satisfied with the support received from their current partner. The top reason for satisfaction was “my partner takes the lead in providing financial security” (45%). Most were very/quite satisfied with the support from family (87%) and friends (96%). Most participants reported a negative reaction or experience as a result of disclosing their hemophilia (friend/colleague/employer, 76%/80%/82%); some reported having felt bullied by peers/colleagues (69%/66%). Majorities reported that past experiences impacted which friends/colleagues they told about their hemophilia, and how or when they disclosed their hemophilia status to these individuals (97%/95%). Seventy-four percent of participants indicated that hemophilia has affected the quality of their sex life; only 54% were extremely/moderately satisfied with their overall sexual relationship. Many reported having had a bleed during sex (40%). Of 150 caregivers of children with mostly mild-moderate hemophilia (74%), 89% were married or in a long-term relationship, and most felt very/quite supported by their partner (98%) and family (87%). Impact on unaffected siblings was more often mixed (49%) than negative (18%). Most felt very/quite satisfied with support of teachers (91%), children at school (80%), and other adults in regular contact (72%). Most caregivers reported negative experiences telling a friend (76%) or having their child tell a friend (69%) about the child’s hemophilia; 43% reported that their child was bullied as a result of having hemophilia.

Conclusion:

While the impact of severe hemophilia on relationships has been reported in HERO and other studies, B-HERO-S suggests that mild-moderate hemophilia B also significantly impacts relationships of affected men/women and boys/girls, especially in terms of disclosure, intimacy, and feeling bullied by peers/colleagues. Opportunities may be explored to more proactively counsel individuals with mild-moderate hemophilia B and families in the setting of comprehensive care to better navigate interpersonal relationships and improve quality of life.

Objective:

Limited evidence supports activity-associated bleeding risk assessment for people with hemophilia (PWH), and consumer materials generically describe types of risk and a single activity risk score based on input from a few physical therapist (PT) authors. The aim of AIR was to assess activity-specific risk ranges, bleed-specific risks, and inherent/modifiable factors that increase risk based on survey/consensus of PT experts.

Methods:

Peer- nominated PTs from US hemophilia treatment centers (HTCs) were invited to participate in a survey regarding ~100 sports/recreational activities. For each activity, respondents provided a low (minimum) and high (maximum) risk assessment on a 5-point scale (low=1, high=5). Position-specific assessments were made for some team sports (eg, baseball pitcher, catcher, and field positions). Sports with distinctly different rules for contact were evaluated separately (eg, flag/tackle football, boys/girls lacrosse, Frisbee/ultimate). Drivers of risk were identified from free text comments and explored at a consensus meeting. Drivers of risk were categorized as inherent, modifiable, activity-driven, and patient-driven.

Summary:

Of 32 invited PTs, 17 responded to the survey with median 26.5 years as a PT and 15.5 years at an HTC; 8 participated in the full-day consensus meeting. Of the survey participants, majorities reported treating adults (94%) and treating children (88%), and most worked in the HTC full- time (29%) or nearly full-time (41%). Overall, few activities had low and high risk assessments both fall within the lower (1) or upper (5) end of the response range. For example, swimming is associated with low risk scores, even when including maximum risk with year-round competitive teams (median low 1, high 2), and tackle football had consistently high scores (median low 5, high 5). Risk scores (median low, high) for some common sports were as follows: baseball pitcher (3,4), catcher (3,4) or other position (2,3); basketball (2,4); hockey (4,5); skiing-downhill (2,4); soccer goalie (2,4) or other position (2,4); snowboarding (3,5). Risks for joint injuries were consistent with position and motion requirements for each sport, while head and muscle bleeds were associated with contact. Key drivers of risk that were identified included progression from seasonal participation to year-round play, overtraining, competitive level, participation in tournaments, and improper body mechanics. Inherent risks included impact with surface/ball/equipment (eg, soccer goalie), impact with players (eg, football), or falls (eg, horseback riding). Modifiable risks included tricks/stunts (eg, skateboarding) and use of safety equipment when not required.

Conclusion:

AIR provides insights into activity-specific risk for PWH including types of bleeding risk and drivers of increased risk. The results may provide a broader framework for assessing activities with respect to bleed site-specific risks and for recognizing how certain activities may be modified to decrease risk or to identify those with non-modifiable inherent risks for injury.

Introduction & Objective:

Standard approaches to prophylaxis may be further improved by taking into account individuals’ pharmacokinetic (PK) profile, thereby increasing the likelihood of therapeutic success [Valentino 2012, Valentino 2014, Lissitckov 2017]. One study demonstrated an association between more time spent above higher FVIII levels (20 and 30%) and lower bleeding rates [Valentino 2016]. Furthermore, a consensus statement proposes to target specific factor levels to tailor treatment for different patient profiles [Iorio 2017]. Additionally, new extended half-life treatments provide physicians with another option to personalize therapy. As more data and therapeutic options become available, it is important to understand physicians’ current perceptions and practice patterns with respect to personalizing haemophilia A care in the US.

Materials & Methods:

Physicians in the US who treat persons with severe hemophilia A and provided informed consent were eligible to complete a cross-sectional, double-blinded web-based survey to evaluate physicians’ perceptions and practice patterns with respect to measuring PK and if/how they personalize FVIII treatment with this information, when and to what extent. This abstract presents results from the first half of the survey which focused on ways in which physicians measure FVIII pharmacokinetics and personalize care.

Results:

Ninety physicians completed the survey. The top three most important considerations for personalizing therapy in general were bleeding history, patient goals, and physical activity. The most commonly cited reason for conducting a PK assessment was product switch (74%) while the most common barrier was patient willingness/availability (60%). Physicians reported using a PK-based approach to personalize treatment in 25% (median) of their severe patients. Of physicians who use PK, trough levels (91%), half-life (58%), peak levels (56%) and Area Under the Curve (22%) were used. While 12% of these physicians reported using all PK parameters, 18% only used trough levels. 23% reported using peak, trough and half-life in combination. Most physicians (89%) indicated using PK data to adjust dose and 50% also used it as a patient education opportunity.

Conclusions:

There was significant variability across respondents as to how PK is assessed and how PK parameters are used in treatment decisions, suggesting an opportunity to increase awareness and use of PK-guided personalization to ultimately improve patient care. Additional education on the definitions and details of PK-guided dosing could help improve overall adoption of this treatment strategy and align the community on what it means to personalize therapy using PK information. More research studying the association between PK-guided prophylaxis and outcomes is encouraged to better understand how best to personalize PK-based prophylaxis for different patient scenarios.

Background:

Hemophilia is an inherited bleeding disorder caused by an impairment in the body’s ability to accomplish the natural clotting process. People with hemophilia experience bleeds because there is an inadequate amount of thrombin due to a deficiency in factor VIII or IX. Thrombin is critical to clotting and sealing the wound by converting fibrinogen into fibrin, reinforcing the primary platelet plug. Thrombin activity is regulated by antithrombin.

Fitusiran is a subcutaneously administered investigational RNA interference (RNAi) therapeutic targeting antithrombin with the goal of improving thrombin generation to promote clotting in people with hemophilia A or B with and without inhibitors. Fitusiran is currently being evaluated as a prophylactic agent for hemophilia A and B with and without inhibitors in an ongoing Phase 2 extension study. Breakthrough bleeds on the study are being managed using replacement factors (non-inhibitor patients) or bypassing agents (BPAs; inhibitor patients). The use of replacement factors or BPAs in the background of fitusiran treatment is of clinical interest and will be described.

Methods:

The Phase 2 extension study (NCT02554773) includes people with hemophilia A or B with and without inhibitors, previously dosed in the Phase 1 (NCT02035605) study. Participants receive monthly, fixed subcutaneous doses of fitusiran, 50 mg or 80 mg. Data on breakthrough bleeds and how they were treated were collected by patient diary.

Results:

As of May 2017, 33 participants were enrolled in the study. Previously reported data demonstrated that fitusiran was generally well tolerated and led to dose-dependent antithrombin lowering, thrombin generation increase, and decrease in bleeding frequency in participants with hemophilia A and B with or without inhibitors. Among those achieving target antithrombin lowering of >75%, few bleed events occurred during the observation period. Bleed events were treated with factor concentrates (FVIII or FIX) or bypassing agents (rFVIIa or aPCC), respectively, in doses according to or lower than recommended by the WFH guidelines. Detailed analyses of the frequency and management of bleed events in the Phase 2 study will be presented.

Conclusions:

Clinical data suggest that fitusiran may be a promising investigational prophylactic therapy to promote appropriate clotting and reduce the frequency of bleeding in people with hemophilia A or B with and without inhibitors. Further, the initial limited experience in treating breakthrough bleeds with replacement factor or BPAs has been encouraging, demonstrating good treatment effect in the absence of identified safety concerns.

Background/Objective:

Hemophilia is a bleeding disorder caused by the body’s inability to accomplish the natural clotting process. People with hemophilia experience bleeds because there is an inadequate amount of thrombin due to a deficiency in factor VIII or IX. Thrombin is critical to clotting and sealing the wound; it converts fibrinogen into fibrin, establishing a network to help more platelets accumulate. Thrombin activity is regulated by antithrombin. Fitusiran is a subcutaneously administered investigational RNA interference (RNAi) therapeutic targeting antithrombin with the goal of improving thrombin generation to promote clotting in people with hemophilia A or B with and without inhibitors. Interim data from the Phase 1 study showed fitusiran was generally well tolerated and administration of monthly fitusiran led to dose-dependent antithrombin lowering, improvement in thrombin generation, and decrease in bleeding frequency. We will report interim safety, pharmacodynamics, and clinical activity of fitusiran from the Phase 2 extension study.

Methods:

The Phase 2 extension study (NCT02554773) includes people with hemophilia A or B with and without inhibitors, previously dosed in the Phase 1 (NCT02035605) study. Participants receive monthly, fixed subcutaneous doses of fitusiran, 50 mg or 80 mg. Primary endpoints include safety and tolerability; secondary endpoints include antithrombin activity, thrombin generation and exploratory evaluation of bleed events.

Summary of Results:

As of May 2017, 33 participants were enrolled in the study and had received continuous dosing of up to 14 months. Previously reported data showed that fitusiran was generally well tolerated, with no serious adverse events related to study drug and no thromboembolic events. Once-monthly subcutaneous dosing achieved dose-dependent antithrombin lowering of ~80% and thrombin generation levels approaching levels similar to participants without hemophilia. Exploratory post-hoc analysis of bleed events showed median annualized bleed rate (ABR)=1 in participants without inhibitors and median ABR=0 in participants with inhibitors. Bleed events were successfully managed with either replacement factors or bypassing agents. Updated safety, tolerability and clinical activity will be presented.

Conclusions:

Emerging clinical data suggest that fitusiran may be a promising investigational prophylactic therapy to promote appropriate clotting and reduce the frequency of bleeding in people with hemophilia A or B with and without inhibitors.

Objective:

Patients with hereditary bleeding disorders have been included in Phase 2 and 3 clinical trials of sofosbuvir (SOF), ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) as well as in a dedicated study (n = 120) in this patient population. This integrated analysis evaluates the safety and efficacy of SOF-based regimens in HCV-infected patients with hereditary bleeding disorders.

Methods:

HCV-infected patients with a medical history of a hereditary bleeding disorder who participated in a SOF-based Phase 2 or 3 study were included in this pooled analysis. Medical history term(s) used to identify patients with bleeding disorders included variations of Hemophilia A or B, Von Willebrand’s Disease, Factor Deficiencies, or conditions associated with hemophilia.

Summary:

A total of 201 patients (74 GT1, 10% GT2, 14% GT3, 2% GT4, <1% GT5) with bleeding disorders were identified across 19 studies. The majority were male (91%), Caucasian (82%), IL28B non-CC (70%), HCV treatment-naïve (55%), and without cirrhosis (74%). Hemophilia A (65%) and B (26%) were the most common bleeding disorders. SVR12 results are shown in the below table by treatment regimen and genotype. The most frequently reported adverse events (>10%) were fatigue and headache; majority were mild or moderate in severity. One patient (<1%) discontinued LDV/SOF due to an adverse event and 11 patients (5%) experienced a serious adverse event. Hemarthrosis, muscle hemorrhage, epistaxis, hematoma, and hematuria were the only hemorrhagic events that occurred in >1 patient. Grade 3 or 4 laboratory abnormalities were infrequent with anemia and hyperbilirubinemia the most frequent Grade 3 laboratory abnormality consistent with RBV administration.

Conclusions:

SOF-based regimens led to high rates of SVR in genotype 1–5 HCV infected patients with bleeding disorders. SOF-based regimens were safe and well tolerated with no new toxicity specific to patients with bleeding disorders emerging
.

Background:

Congenital FXD is a rare bleeding disorder characterized by spontaneous joint and mucocutaneous bleeding and gastrointestinal or intracranial hemorrhage. pdFX is a US- and EU-approved treatment for congenital FXD, but data in children <12 years have been unavailable.

Aims:

To investigate pdFX efficacy, safety, and pharmacokinetics in children <12 years with moderate to severe congenital FXD.

Methods:

In this 6-month, open-label, multicenter, phase 3, prospective study in children <12 years, all subjects had a confirmed diagnosis of moderate to severe congenital FXD (basal FX:C <5%), severe bleeding history, or an F10 gene mutation causing a documented severe bleeding type. Subjects received routine prophylaxis at recommended 40–50 IU/kg twice weekly to maintain trough FX:C levels ≥5%. Each investigator assessed efficacy based on standardized criteria and presence of breakthrough bleeding. All subjects provided informed consent and the protocol was approved by appropriate independent ethics committees.

Results:

Mean age of the 9 trial completers was 6.8 years. Eight subjects had severe and 1 had moderate FXD. Overall, 537 prophylactic infusions were administered; mean dose/child was 38.6 IU/kg. Ten bleeds in 3 of 9 children were reported: 6 minor, 3 major, 1 unassessed. Investigators rated overall pdFX efficacy as excellent in all subjects. Overall mean incremental recovery was 1.74 IU/dL per IU/kg. FX trough levels were maintained >5% after visit 4 (days 29–42) in all subjects.

A total of 28 treatment-emergent adverse events (TEAEs) were reported in 8 children; none were considered pdFX related. No significant changes were noted in vital signs, physical exams, or laboratory measurements. No evidence of inhibitor development was seen.

Conclusion:

pdFX is efficacious in the prophylaxis of bleeding episodes in subjects <12 years with moderate to severe FXD. Safety profile in this population is consistent with previous results in subjects ≥12 years.

Funding: Bio Products Laboratory

Objectives:

The primary aims of this study are to 1) evaluate the prevalence of depression and anxiety among adult persons with hemophilia (PWH) and 2) explore relationships between depression, anxiety, chronic pain, and adherence to clotting-factor treatment.

Method:

This study used a subset of data from the IMPACT QoL II, a one-time, cross-sectional survey of 200 adults (age >18) with self-reported diagnosis of either Hemophilia A or B who were able to read, write, and speak English. The study was approved by the IRB in the primary investigator’s institution. Participants were a convenience sample recruited at bleeding disorders conferences in 2013-2014 and issued a randomly generated identification number to ensure anonymity. The 139-item survey was completed electronically through SurveyMonkeyTM on a study computer tablet. Participants were given $20 upon completion of the survey, which took 15-45 minutes to complete. The subset of variables evaluated for this analysis included the Faces of Pain Scale-Revised (FPS-R) (chronic pain), level of control over pain each participant feels they have, adherence to clotting factor measured by total scores (higher score=lower adherence) on the VERITAS-PRO or VERITAS-PRN, anxiety measured by the GAD- 7, depression measured by the PHQ-9, and self-report of ever receiving a diagnosis of depression and/or anxiety. The cut-off score for presence of moderate to severe depression or anxiety was 10 on both the PHQ-9 and the GAD-7, scores which have been validated by previous literature in other populations. Lower vs. higher adherence was defined by VERITAS scores in the highest and lowest quartile respectively.

Summary:

Participants with lower treatment adherence (VERITAS score >57) were more likely to have PHQ-9 scores >10 (P=0.02). GAD-7 scores >10 also demonstrated a trend to be associated with lower treatment adherence (P=0.15). 28% of participants reported a diagnosis of depression, but 53% with PHQ-9 scores >10 had not been diagnosed with depression. Similarly, 22% reported a diagnosis of anxiety but 52% with GAD-7 scores >10 had not been diagnosed. Participants who reported non-control of pain were more likely to have PHQ-9 scores or GAD-7 scores >10 (P=0.001 and P=0.013 respectively). There were significant correlations between PHQ-9 and GAD-7 (Rho=0.76, P<0.0001), PHQ-9 and FPS-R (chronic pain) (Rho=0.31, P=0.003), and GAD-7 and VERITAS (P=0.005). These data indicate that depression and anxiety are associated with greater severity of chronic pain, and depression is associated with poorer adherence to clotting factor treatment regimen (prophylaxis or other regimen). Both depression and anxiety appear to be under-diagnosed in PWH.

Objective:

This study assessed current clinical practices of clinicians related to hemophilia treatment guidelines to identify knowledge, competency, practice gaps and barriers to optimal care of patients with inhibitors.

Methods:

A continuing medical education (CME)-certified clinical practice assessment survey was developed comprising 24 knowledge- and case-based, multiple-choice questions. The survey assessed knowledge, attitudes, and confidence with regard to newly-developed hemophilia treatment guidelines emphasizing integrated care for patients with inhibitors, and the application of these guideline-based recommendations. The survey launched on the Medscape Education website on December 5, 2016 with participant responses collected through January 26, 2017. The data sample includes responses from 170 physicians who participated during the study period.

Summary of Results (n=170 physicians):

Responses to questions on the screening for, and management of, inhibitor formation in patients with hemophilia undergoing prophylaxis, showed that: the majority of hematologists/oncologists correctly identified the factors that increase risk of inhibitor formation (71%), while less than half of pediatricians did so (46%); when asked regarding exposure days (EDs) and the formation of inhibitors, half of hematologists/oncologists correctly identified within 50 EDs, while only 25% of pediatricians did so; and both hematologists/oncologists (21%) and pediatricians (28%) incorrectly identified how often a patient should be tested for inhibitors. When surveyed specifically regarding immune tolerance induction (ITI), a slight majority of hematologists/oncologists and pediatricians correctly chose the time frame during which to initiate ITI (55% and 51%, respectively), and 50% of hematologists/oncologists knew the most powerful predictor of ITI success, while only 42% of pediatricians did so; only 14% of hematologists/oncologists and 4% of pediatricians knew that there is no optimal rFVIII to initiate for ITI; only 10% of hematologists/oncologists and 8% of pediatricians knew that there is not optimal dose of rFVIII to initiate for ITI.

Conclusions:

The need for further education was observed for the following topics: best practices in the integrative care of patients using evidence-based guidelines and recommendations; current and emerging clinical data guiding acute and prophylactic management; risk factors for the development of inhibitors during prophylaxis; screening and management of inhibitor formation, including ITI. Further educational efforts tailored to address these gaps are warranted.

Objective:

Physicians prescribing Factor VIII for haemophilia A patients are presented with an array of dose and dose frequency in the package insert making it difficult to precisely prescribe. To clarify the treatment outcome across products, a model of the published half-life was used to provide the expected % IU/dl +/- SD at 24, 48, 72, and 96 hours post dose at a normalized dose and at the high end of the recommended dosage (dose and freq.).

Methods:

Eleven rFVIII products recently marketed in the US were assessed using a model of the halflife +/- SD to calculate the expected %IU/dl +/- SD at 24, 48, 72, and 96 hrs post-dose. Terminal half-life data for adults was obtained from each published package insert (PI). The one-stage clotting assay data was used for all except Afstyla© (chromogenic assay only). Variance reported as coefficient of variation or confidence intervals was converted to standard deviation.

The first comparison was made using a standard dose of 50 IU/kg across all products. The second comparison used the maximum recommended dose and frequency for routine prophylaxis defined in the PI. Full data sets and curves of %IU/dl+/-SD under standard doses of 50 IU/kg and under maximum dose and frequency for routine prophylaxis have been generated.

Summary:

Graphing the single dose comparison (50 iu/kg) revealed 3 general clusters and one outlier at 24 hrs post dose. The first cluster had 4 products with a mean range of 21-25 %IU/dl at 24 hrs post dose. The second cluster had 5 products with a range of 30-32 %IU/dl at 24 hrs. The third cluster had 1 product (Eloctate©) with 43% IU/dl at 24 hrs. The outlier (Nuwiq©) showed exceptional variance compared to others and removed from discussion.

Expected %IU/dl was recalculated using the most frequent and highest dose recommended for individual products. Assessing the –SD value: 10 of 10 products achieved > 1% trough at 24 hrs; 8 of 10 at 48 hrs; 2 of 10 at 72 hrs; and 1 of 10 at 96 hrs. Note at 72hrs, only 2 of 10 products achieve minimal trough at –SD level when 4 of 10 claim q3day dosing.

Conclusions:

Initial dosing for routine prophylaxis relies on the mean half-life. The PK parameters are based on only 18 to 30 patients under well-controlled conditions. There is waste on both sides of the PK half-life distribution curve. Would it be reasonable to assure minimal breakthrough bleeds and less over-dosage by initiating treatment with a personal PK profile for each patient in order to identify the correct dose and frequency? This model could be used to find optimal dose and frequency with input from a personalized product half-life.

Objectives:

To streamline and standardize the transition process of care through improved collaborations with staff and for persons with hemophilia transferring from a pediatric to an adult HTC. Processes were developed to provide patients with documented transition skills in order to foster medical independence in a complex healthcare environment.

Methods:

Continuous quality improvement tools were used to develop, implement and test a standardized transition tool for patients diagnosed with hemophilia A or B, ages fifteen to nineteen years of age. The transition tool was designed to assess the knowledge and skills of the adolescent in preparation for transition to adult care. Adherence to the administration of the tool in the pediatric HTC was the initial outcome measure. Key drivers included 1) improving communication between staff at the HTCs 2) transition tool development 3) educational resource content identification and 4) education of staff and families regarding the transition project. Communication was fostered through weekly team meetings to discuss and develop the transition tool in collaboration with the adult HTC. The adult HTC social worker would then attend the comprehensive clinic appointment at the pediatric HTC for those identified patients to assist in the preparation of transferring care. An excel spreadsheet, along with the ATHN database, was utilized to track patients to provide continuity of care during the transfer. Additionally, quarterly meetings were implemented with both HTC teams to discuss transferring patients and the continuum of the transition process. The transition tool was developed after review of available transition tools and was designed to provide systematic assessment of patient knowledge for transition readiness. The tool was refined through a series of PDSAs and implemented at each comprehensive clinic. The patient responses to the transition tool highlighted educational opportunities and led to the development of a resource cart to provide readily accessible targeted educational tools. Family and staff were educated about the value of transition readiness through team meetings, community outreach and during clinic visits.

Summary:

Use of the transition tool began in March 2016. Data was available through May 17, 2017. Thirty of 31 (97%) eligible patients completing the tool. Communication was improved between HTC teams. Educational tools were identified, obtained and provided to patients.

Conclusions:

We have successfully streamlined and standardized the transition process, identified educational opportunities and improved communication with staff at our HTCs utilizing established quality improvement techniques. Next steps include measurement of answered transition tool questions to further enhance patient/family knowledge and promote successful transition, as well as expansion to other age appropriate transition tools, to facilitate the journey to medical independence.

Background:

Factor VIII (FVIII) pharmacokinetic (PK) parameters and other patient characteristics may play a role in effectiveness of FVIII prophylaxis. Objective: A post-hoc analysis was conducted to assess the association between PK parameters and BAY 81-8973 (Kovaltry® ) prophylaxis regimen in patients with severe hemophilia A.

Methods:

LEOPOLD I was a randomized, open-label, phase 2/3 trial to investigate use of BAY 81-8973 routine prophylaxis for treatment of bleeds in adolescents and adults with severe hemophilia A. In the efficacy part of the trial (part B), patients received BAY 81-8973 at a dose of 20‒50 IU/kg 2x/week (n=18) or 3x/week (n=44) for 12 months. Prophylaxis regimens were determined by study investigators, independent of BAY 81-8973 PK data. A subset of 20 patients (2x/week, n=7; 3x/week, n=13) had data from an earlier PK study (part A), in which patients received a single 50-IU/kg injection of BAY 81-8973 and had blood samples collected over 48 hours to assess PK parameters, including area under the curve (AUC), half-life (t½), and clearance (CL). Estimates of PK parameters were also derived using a population PK model based on data from all patients. This analysis compared model-based PK parameters, baseline characteristics, total annual dosing, and bleed outcomes between 2x/week and 3x/week prophylaxis groups. A similar analysis was done among the subset of patients in part A who had PK data. Differences between 2x/week and 3x/week dosing were assessed using Wilcoxon rank sum tests for continuous variables, and chi-square or Fisher’s exact tests for categorical variables.

Results:

In the full trial population, model-based AUC [mean (SD): 1957.1 (648.3) vs 2139.1 (875.7), 2x/week and 3x/week, respectively], t½ [15.0 (3.7) vs 15.9 (6.6)], and CL [0.028 (0.009) vs 0.027 (0.011)] were comparable between groups. The proportion of patients with ≥3 bleeds at 12 months was 33% for 2x/week and 48% for 3x/week. The 3x/week group had more bleeds in the past 12 months, higher baseline Gilbert bleeding scores, were more likely to have target joints at baseline, and received higher doses of BAY 81-8973 during the 12- month treatment period. In the part A subset analysis, observed and model-based AUC, t½, and CL were similar in both groups. The proportion of patients with ≥3 bleeds at 12 months was 0% for 2x/week and 46.2% for 3x/week (P=0.052).

Conclusions:

The similarity of PK parameters in patients successfully treated with 2x/week and 3x/week regimens suggests that clinical factors other than t½, AUC, and CL are important in predicting success of prophylaxis with BAY 81-8973. Physician decisions, taking into consideration clinical factors to identify appropriate patients for specific prophylaxis regimens, appear to be an important factor for 2x/week or 3x/week dosing with BAY 81-8973. These factors should be considered when individualizing BAY 81-8973 prophylaxis frequency.

Background:

Accurate measurement of factor VIII (FVIII) activity in patients with hemophilia A is important for patient monitoring and treatment decisions. Discrepancies in results using different assays or reagents to measure prolonged–half-life factor products have been recognized. BAY 94-9027 is a prolonged–half-life FVIII product site-specifically conjugated with a 60-kDa polyethylene glycol molecule (2×30 kDa branched).

Objective:

A global field study was conducted to assess the ability of clinical laboratories to measure BAY 94-9027 activity in spiked hemophilic plasma samples using their in-house or specific assays.

Design/Method:

In this 2-part study, laboratories received sample sets (3–4 per laboratory) of 26 blinded samples in randomized order for analysis. Each set consisted of triplicate test samples of BAY 94-9027 or a comparator (antihemophilic factor [recombinant] plasma/albumin-free method [rAHF-PFM (Advate® ); Shire]) spiked at low (<10 IU/dL), medium (10–50 IU/dL), and high (50–100 IU/dL) concentrations in pooled hemophilic plasma. Normal control plasma and unspiked hemophilic plasma in triplicate were positive and negative controls, respectively. Two additional blinded samples matching 2 of the other 24 samples in the set were included in each set to decrease the predictability of each set. Laboratories analyzed test samples using their in-house assays (one-stage, chromogenic, or both), reagents, and standards (part 1). In part 2, all laboratories tested 2 additional sample sets using 2 activated partial thromboplastin time kits (Pathromtin® and HemosIL® SynthASil) previously shown to accurately measure BAY 94-9027 and full-length FVIII. FVIII recovery and FVIII levels were primary and secondary endpoints, respectively.

Results:

Fifty-two laboratories in North America, Europe, and Israel participated in the study. In part 1, 49 laboratories tested samples using the one-stage assay, 16 used the chromogenic assay, and 13 used both assays. The reagents routinely used for measuring FVIII activity varied among participating laboratories. Mean FVIII recovery ranged from 75.1%‒103.2% for BAY 94-9027 and 94.6%‒114.7% for rAHF-PFM across all concentrations and reagents using the one-stage assay. As expected based on previously published data, the PTT-A and HemosIL® APTT-SP kits underestimated BAY 94-9027 at all concentrations. More accurate one-stage results were generated using the Pathromtin® and SynthASil kits, as shown in part 2 of the study. For the chromogenic assay, mean FVIII recovery ranged from 104.4%‒117.1% for BAY 94-9027 and 87.7%‒107.8% for rAHF-PFM across all concentrations.

Conclusion:

BAY 94-9027 can be accurately monitored using the chromogenic assay and select commonly used one-stage assay kits without need of a conversion factor.

Background:

For people with hemophilia, mild trauma can cause internal joint bleeding resulting in stiffness and pain, limited range of motion and irreversible bony changes. Ankle pain may occur early in life affecting the ability to participate in activities of daily living, work and leisure. The purpose of this study was to explore experiences and priorities of people with hemophilia regarding their foot and ankle function, activity and participation.

Methods:

Eleven participants with hemophilia A or B, twenty-one years and older with a history of ankle pain, were recruited. Semi structured interviews were recorded, transcribed and then analyzed for themes with NVivo 10 Software.

Results:

Themes: (1) "Pain impacts my daily life, but I still have to get things done." (2) "Management of ankle function is highly individualized." (3) "Self-advocacy is crucial." (4) "I want healthcare providers who listen to me and respect my knowledge."

Conclusions:

For our participants, ankle pain and dysfunction impact daily life. Expressed themes highlighted priorities for participation, health management and desired healthcare.

Discussion:

As health care moves from volume-based to value-based care delivery, the patient’s voice is increasingly important in prioritizing interventions. The participant-identified priorities and experiences from our study can begin to inform healthcare providers, allowing them to deliver more targeted care for their patients with hemophilia.

Aim:

The goal of this project was to gather data and identify factors affecting access to dental care for people with bleeding disorders in the United States.

Methods:

The Arizona School of Dentistry and Oral Health and the National Hemophilia Foundation conducted a joint survey. The survey was completed by 102 of the 147 hemophilia treatment centers (HTC) in the USA. This represents 69% of the HTC’s in the country. Each HTC provided specific information concerning the dental services and education provided for patients.

Summary:

Survey results revealed inconsistent levels of oral health services available to patients. Major factors limiting access to care include finances, patient anxiety and a lack of providers with the skills to treat this population.

Conclusion:

Improvement in oral health for persons with bleeding disorders requires appropriate education for providers, patients and families. Additionally, both public and private health funding must be re-evaluated as it relates to people with bleeding disorders.

Background:

Activity limiting joint disease has greatly decreased with the introduction of prophylactic treatment for people with severe bleeding disorders. Previous research using the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition (BOT-2TM), a standardized, normative, age and sex matched test of motor development, suggested motor development of males aged 4-21 years with bleeding disorders may be lower than age-matched peers.

Objective:

The primary purpose of this study was to compare the gross motor proficiency of boys with hemophilia ages 4-21 years followed at the Hemophilia Center at Oregon Health & Science University utilizing the BOT-2. Secondarily, we examined the relationship between joint health and gross motor proficiency.

Methods:

1. a)  Participants and setting: Thirty-four subjects with either hemophilia A or B were recruited

   from our center. Data collection occurred during clinic visits or at the patients’ homes.

2. b)  Design and Procedures: A prospective, cross-sectional study design was used. The Upper Limb Coordination, Bilateral Coordination, Balance, Running Speed and Agility, and Strength subtests of the BOT-2 were administered. Body composition, range of motion, presence of an inhibitor, and use of prophylaxis were collected at the time of testing or from chart review.

3. c)  Analyses: Analysis of variance (ANOVA) modeling was used to compare BOT-2 scores of PWH with baseline BOT-2 scores estimated from the general population of comparable age.

Summary:

Mean Running Speed & Agility scores were greater among boys with hemophilia compared to the control population (p=0.0026). Agility scores were similar between boys with hemophilia A and B (p>0.60), and significantly greater compared to the control group (p=0.0153). No other significant differences were found comparing boys with hemophilia to the control group. Within the boys with hemophilia cohort, age-adjusted ANOVA found no significant differences in BOT-2 scores between subjects of different severities, treatment regimen (prophylaxis or episodic), or diagnoses (Hemophilia A or B).

Conclusion:

Boys with hemophilia have the same or better gross motor proficiency as age matched peers.

Attainment of self-management skills, disease knowledge, and a documented transition plan are key elements for smooth transfer from pediatric to adult care for patients with chronic disease. Our hemophilia center had no standardized approach for assessing key patient competencies or independence readiness. In the last quarter of 2014, our team undertook a quality improvement project; we developed a transition tool with the goals of consistently assessing self-efficacy skills at a sustained rate of 90% during annual comprehensive visits; and developing patient-centric skill-building plans based on these assessments.

We previously reported that after four PDSA ramps of tool utilization, 31 patients, age 2-21 years, had been seen in hemophilia comprehensive clinic during the 3 month period studied. Utilizing the newly developed tool, 97% had a global assessment of competency with respect to their current age group; 93% had transition or progress plans documented. This demonstrated significant improvement compared with retrospective data from the three month period prior to implementation of the tool.

Since this previous report, we have continued to utilize the tool during hemophilia comprehensive clinic. In the proposed poster, we will demonstrate sustainability of the tool through analysis and presentation of Hemo-milestone data from the first half of 2015. Further, based on these results we will propose additional areas of study inspired by the transition tool, with the aim of continued improvement of the skill-building and transition process. These include improved utilization of educational materials based on identified learning needs; evaluation of documented, planned interventions; the development of collaborative educational events with our partner adult HTC; and retrospective, patient- centered evaluation of the transition process after the transition to adult hemophilia care.

Objective:

Personalizing treatment to a patient’s lifestyle and promoting overall health and wellness in persons with hemophilia (PWH) is essential to optimizing outcomes. There is limited evidence that correlates how activity and infusions impact bleeding episodes and further data on this relationship is needed. The research objective of SPACE is to prospectively explore the association between activity level, timing of infusion, and occurrence of a bleeding episode in PWH using novel technology.

Methods:

This six-month prospective, observational study includes PWH A or B in the United States currently receiving ADVATE or RIXUBIS between the ages of 13 and 65 years. Enrolled PWH use a smartphone eDiary application to log information on activities, infusions, and bleeding episodes. As an additional measurement of activity, enrollees are given a FitBit, a consumer-based activity tracker that measures steps taken and calories burned. Activity types are assessed based on their level of perceived risk for collision, according to the NHF “Playing It Safe” brochure. We report here current study status and descriptive analysis of baseline data.

Results:

The interim analysis included 15 patients with a median age of 19 (Range: 13 to 47). At baseline, 87% of patients were on prophylaxis and 13% treated on-demand treatment. Fifty-three percent of patients had 0 target joints at baseline. Eighty-seven percent of patients indicated that they had discussed activity participation with their physician. Sixty-seven percent of patients considered themselves ‘very satisfied’ or ‘satisfied’ with their level of activity. Data collected from the FitBit indicated that patients in SPACE walked on average 7,367 (SD: 3250) steps per day and burned 979 (SD: 398) calories from their activity. For patients on prophylaxis, the mean number of days per week doing mild, moderate and strenuous activity were 3.57, 2.64, and 1.5 respectively. Of the data reported on bleeding episodes, 40% of patients reported no bleeds at the time of the interim analysis. Forty percent of patients did not report having a bleed at the time of the interim analysis. Of all bleeds reported, 34% were associated with physical activity.

Conclusions:

Current data from SPACE demonstrates that subjects are active and participating in various activities. Continued data will provide better understanding of the types of activities and infusion schedules that may be associated with risk as well as protective effects on bleeding episodes by infusing prior to activity. A personalized approach to treatment based on physical activity levels may minimize bleeding risk in PWH.

Background:

Until recently, the hemophilia B community has only had standard Factor IX (FIX-Fc) products as treatment choices. With the availability of additional standard rFIX products and extended half-life (EHL) rFIX-Fc, there has been much debate (1-4) regarding clinical and cost expectations, balanced with optimizing use in patients. To level the debate, an understanding of real-world prescription costs of patients who switch to EHL FIX-Fc products is warranted.

Objectives:

1) To characterize patients who switch from rFIX to EHL rFIX-Fc, and 2) to understand their change in factor costs.

Methods:

Retrospective analysis using national US specialty pharmacy dispensing databases from Jan 1, 2013-Apr 25, 2015 of Hemophilia B (ICD-9 code 286.1) individuals who switched from rFIX to rFIX-Fc. Descriptive statistics summarized patient characteristics. Patients who had at least 90 days of prescription coverage on both products were included. Utilization was averaged on a monthly basis pre and post switch. Costs were calculated by multiplying the units by the wholesale acquisition prices for each product (Red Book) and the percentage change in cost from rFIX to EHL-rFIX was compared. This analysis studied patients who switched but stayed on similar regimens. Cohorts were characterized as prophylaxis to prophylaxis (P to P), or on-demand to on-demand (OD to OD).

Results:

Sixteen switchers were included in the study. Hemophilia severity was reported as 62.5% severe, 12.5% moderate, 6.25% mild, and 18.75% of unknown severity. The P to P cohort comprised of the majority of patients at 87.5% (n=14) while OD to OD were smaller at 11% (n=2). The median ages for these cohorts were similar. The P to P median age was 15 (range: 5-51) and OD to OD was 14 (range: 13-15) years old. Median prescription costs increased in the P to P cohort by 40% (range: -56% to 181%), while OD to OD increased by 173% (range: 1% to 348%).

Conclusion:

While the availability of EHL rFIX-Fc allows hemophilia B patients an option with less frequent infusions, our findings demonstrate that for those who initially switched from prophylaxis to prophylaxis or from on-demand to on-demand regimens, costs increased for the majority of patients. This analysis provides initial real-world cost data for those who have switched to EHL and may be helpful in decision makers’ understanding of the value of EHL rFIX-Fc in hemophilia B.

Objective:

BAX 855 is an extended half-life recombinant Factor VIII based on ADVATE. It was developed as an option to further personalize care and improve outcomes in people with hemophilia A. As a new therapy, it is important to understand patient satisfaction and preferences relative to their prior treatment. The objective of this research was to describe patient satisfaction with and preference for their prior FVIII therapy and BAX 855 as reported in the pivotal trial.

Methods:

BAX 855 was studied in a 6-month, phase 2/3, multi-center, open label study. Subjects in Arm A received 45 ± 5 IU/kg of BAX 855 twice weekly while subjects in Arm B infused BAX 855 on-demand. Patient preference and satisfaction were included as exploratory endpoints. Patient satisfaction was captured with the following options describing their treatment: very satisfied, satisfied, neither satisfied nor dissatisfied, or very dissatisfied at baseline for their prior FVIII therapy and at follow-up for BAX 855. Patient preference for BAX 855 or their prior FVIII therapy was captured at follow-up. Ethics approval and informed consent were obtained. The percent of very satisfied and satisfied patients were combined for this analysis. Results were reported for all patients and by treatment arm.

Summary:

138 patients were in the intent to treat (ITT) sample. The majority of patients in the ITT sample completed the satisfaction questionnaire, however the number varied slightly by question and visit. While 79.4% (100 of 126) of patients were satisfied with their prior FVIII at baseline, satisfaction increased to 90.1% (109 of 121) with BAX 855 and 84.7% (100 of 118) preferred BAX 855 over their prior FVIII. Of the 85 patients in Arm A previously on prophylaxis, 18 patients in Arm A previously on-demand, and 15 patients in Arm B previously on-demand, 83.5%, 88.9% and 86.7% preferred BAX 855 over their prior FVIII, respectively.

Conclusion:

Notably, patients enrolled in the BAX 855 trial had a high degree of satisfaction with their prior FVIII therapy. Nonetheless, treatment with BAX 855 was successful in further improving patient satisfaction with the majority of patients preferring it over their prior FVIII product.

Objective:

To assess pain and functional impairment through 5 patient-reported outcome (PRO) instruments in non-bleeding adults with hemophilia.

Methods:

Adult men with hemophilia (mild-severe) with history of joint pain/bleeding completed a hemophilia/pain history and 5 PROs (EQ-5D-5L with visual analog scale [VAS], Brief Pain Inventory v2 [BPI-SF], International Physical Activity Questionnaire [IPAQ-SF], SF- 36v2, and Hemophilia Activities List [HAL]) during routine visits. Initial patients were asked to complete the PROs again after their estimated 3-4 hour visit (retest population). PRO scores were calculated from published algorithms. Generally, higher scores indicate better health- related quality of life (HRQoL) and functional status, and greater pain severity/interference.

Summary:

381 Patients were enrolled between October 2013 and October 2014; 164 of the initial 187 completed the retest and are reported here. Median time for completion of the initial survey/PROs was 36.0 minutes and 21.0 minutes for the PRO retest. Most retest subjects had hemophilia A (74.4%) and were white-non-Hispanic (72.6%). Median (Q1, Q3) age was 33.9 (26.9, 46.0), 48.7% were married, 62.6% had some college or graduate education, 80.7% were employed, and 61.0% were overweight or obese. HCV (49.4%) was more common than HIV (16.5%); 61.0% self-reported arthritis/bone/joint problems. Median EQ-5D- 5L VAS was 80.0 (0-100 scale), and EQ-5D-5L health index 0.80 (-0.11-1 scale); 61.6% reported any problems with mobility (29.3% reported moderate/severe problems), 55.8% with usual activities (18.4% moderate/severe), and 22.0% with self-care (4.3% moderate/severe). 73.2% reported pain-discomfort (43.3% moderate/severe), and 41.1% anxiety-depression (14.7% moderate/severe). For BPI, median pain severity was 3.0 (0-10 scale) and pain interference 2.9 (0-10 scale); median worst pain was 6.0, least pain 2.0, average pain 3.0, and current pain 2.0. Pain most impacted general activity, mood, walking ability, and normal work, and least impacted relations with other people. Ankles were the most frequently reported site of pain. Median IPAQ total activity was 693.0 MET/min/week; 49.3% reported no activity in the prior week. Median SF-36v2 scores (0-100 scale) were lower for physical health (39.6) than for mental health (51.6). Median overall HAL score was 76.1 (0-100 scale); complex lower extremity activities were the most impacted activity domain.

Conclusions:

These 5 PRO instruments provide different levels of detail describing the impact of hemophilia on pain and function, and consequently, have varied burdens of administration. PRO data from the retest population demonstrate that most adults with hemophilia experience pain and functional impairment that impacts HRQoL, highlighting the importance of assessments and patient dialogue.

Background and Objective:

Standard outcome measures in hemophilia, such as the annual bleeding rate, have inherent limitations in both clinical practice and in research, including lack of both sensitivity and personalization. Goal attainment scaling (GAS) is a method for evaluating outcome that is patient-centered and sensitive to change in individuals and populations; collaborative goal setting may also be viewed through the biopsychosocial lens as a potential resource to strengthen disease-related coping. GAS has been used successfully in several disease areas. However, feasibility can be an issue. To address this, standardized goal attainment menus can be developed that preserve individualization, while allowing greater ease of use by non-experts. We initiated a process to develop a novel outcome measure in hemophilia, the GAS-Hem, by creating a goal attainment menu for patients living with hemophilia.

Methods:

We conducted 2 multidisciplinary workshops with participants from medicine, nursing, social work, and physical therapy (n=12). During the first workshop, we developed a list of goal areas, each with an associated set of descriptors of attainment levels. At the second workshop, a second group of experts (n=8) critically reviewed each goal to evaluate its importance and relevance for inclusion in the GAS-Hem.

Summary:

28 goal areas with associated descriptors of attainment levels were developed, covering 3 broad categories: ability to manage hemophilia, ability to recognize and treat complications, and ability to cope with the impact of hemophilia on daily life. Descriptors incorporated several key parameters for each goal (eg. skill level, desire for change, utilization of available resources) (Table).

Conclusions:

We developed a novel, patient- centered outcome measure for patients with hemophilia. A comprehensive, preliminary list of goal areas and attainment levels was successfully created. The next step will be to incorporate feedback from patients and families, after which a feasibility study will be conducted to evaluate content and construct validity and overall ease of use.

Table. Examples of Goal Areas and Descriptors

Background:

BAY 1093884 is a fully human monoclonal antibody against tissue factor pathway inhibitor developed as a bypass agent for hemophilia patients with inhibitors. It restores thrombin burst, leading to stable clot formation in hemophilic conditions in vitro and effectively stops bleeding in vivo.

Aims:

Efficacy and thrombogenic potential of BAY 1093884 were evaluated in bleeding models in acquired hemophilia A rabbits and the Wessler venous stasis model, respectively.

Methods:

The efficacy of BAY 1093884 was tested in rabbit bleeding models. Anti-factor VIII antibodies rendered rabbits hemophilic, increasing bleeding time by ~3-fold (median 120–390 seconds) in an ear bleeding model and >7-fold (median 240–1800 seconds) in a saphenous vein bleeding model. In the Wessler model, thrombosis was induced by complete ligation of the jugular vein after administration of BAY 1093884, recombinant FVIIa (rFVIIa), or activated prothrombin complex concentrate (aPCC) to measure in vivo hypercoagulability.

Results:

In both bleeding models, BAY 1093884 corrected bleeding time close to normal in a dose-dependent manner. A statistically significant reduction in saphenous vein bleeding was reached at 1 and 3 mg/kg BAY 1093884, reducing bleeding time to 330 and 240 seconds, respectively. In contrast, 1 mg/kg rFVIIa only slightly reduced bleeding time to a median of 1200 seconds. In the Wessler model, 1 mg/kg rFVIIa and 40 IU/kg aPCC resulted in thrombus formation, reaching full occlusion in rabbits with normal coagulation system. In contrast, BAY 1093884 up to 100 mg/kg did not fully occlude, and only showed a slight increase in localized clot formation over baseline, which could be completely prevented by an anticoagulant. In addition, no stasis-triggered thrombi were seen in hemophilia A rabbits treated with BAY 1093884, indicating reduced thrombogenicity risk for BAY 1093884 in patients with hemophilia.

Conclusions:

These studies showed that BAY 1093884 potently controls bleeding in hemophilic rabbits while showing reduced thrombogenic risk compared with the current standard of care.

Introduction and Objectives:

The phase 3 A-LONG and Kids A-LONG studies demonstrated the safety and efficacy of rFVIIIFc for the control and prevention of bleeding episodes in subjects with severe hemophilia A. This subgroup analysis of A-LONG and Kids A-LONG examined bleeding frequency with rFVIIIFc prophylaxis in subjects with target joints at baseline.

Methods:

A-LONG (≥12 y) and Kids A-LONG (<12 y) subjects with a history of target joints (a major joint with ≥3 bleeding episodes in a 6-month period) who were previously treated with FVIII and received on-study rFVIIIFc prophylaxis were identified. Self-reported pre-study 12- month bleeding history and on-study annualized bleeding rate (ABR) for all bleeds were evaluated.

Results:

93/141 subjects in A-LONG and 13/69 subjects in Kids A-LONG had target joints at baseline. The most prevalent locations of pre-study target joints identified at baseline among subjects in A-LONG were the elbow (61.7%) and ankle (59.6%). Similarly, in Kids A-LONG, these were the ankle (69.2%) and elbow (30.8%). A total of 59.7% and 52.4% of subjects receiving individualized (Arm 1) and weekly (Arm 2) rFVIIIFc prophylaxis in A-LONG, respectively, and 53.8% of subjects receiving rFVIIIFc prophylaxis in Kids A-LONG with target joints at baseline had no target joint bleeding episodes on-study. Median on-study ABRs with rFVIIIFc prophylaxis tended to be lower than pre-study bleeding rates in subjects with target joints at baseline (Table).

Conclusions:

For subjects with severe hemophilia A who had target joints at baseline, rFVIIIFc prophylaxis lowered bleeding rates across age groups compared with pre-study FVIII treatment.

Objective:

Hemophilia is marked by frequent joint bleeding, resulting in acute and chronic pain and functional impairment. Surveys in US adults with hemophilia demonstrate suboptimal pain management and quality of life (QoL). The objective of P-FiQ was to methodologically assess QoL parameters, including functional impairment and pain, and pain management strategies.

Methods:

Adult men with mild-severe hemophilia with a history of joint pain and/or bleeding completed a hemophilia/pain history and various patient-reported outcome assessments (completed twice in “retest” population of initially enrolled patients).

Summary:

Of 164 adults with hemophilia (median age 34) in the “retest” population, more had hemophilia A (74%) than B (26%); 6% had inhibitors. Most had some college-or-above education (63%), 81% were employed, 61% were overweight/obese, and 61% self-reported arthritis/bone/joint problems. Current patient-reported treatment regimens were prophylaxis (42%), on-demand (39%), or mostly on-demand (19%; 25/31 using infusions ahead of activity). One-third (32.9%) reported unrestricted school/work/recreational activities in the prior 6 months; 6.2% reported needing assistance for school/work/self-care, or did not participate in recreational activities because of pain, loss of motion, and weakness. Some patients (31.3%) reported using a cane/crutches/walker (3.8% always) and 7.6% a wheelchair (1.3% always), and 47.0% reported a history of joint surgery (41 knee, 37 ankle, 29 elbow). Patients reported losing an average of 3.7 and 1.8 school/work days in the previous 6 months due to lower and upper extremity problems, respectively. Patients reported that during the prior 6 months they had experienced acute pain only (24%), chronic pain only (33%), or both (29%); 15% reported no pain. Acute pain was most frequently described as sharp (77%), aching (66%), shooting (57%), and throbbing (55%), and chronic pain as aching (74%), nagging (49%), throbbing (44%), and sharp (40%). Most common analgesics in the past 6 months for acute/chronic pain were acetaminophen (69%/58%), NSAIDs (40%/52%), hydrocodone-acetaminophen (29%/33%), oxycodone (12%/11%), and oxycodone- acetaminophen (9%/8%). Most common nonanalgesic treatment strategies reported for acute/chronic pain in the past 6 months were ice (73%/37%), rest (48%/34%), factor or bypassing agent (48%/24%), elevation (34%/28%), relaxation (31%/23%), compression (27%/21%), and heat (25%/15%); other reported strategies include medical marijuana (17%/9%), physical therapy (12%/9%), prayer (11%/8%), faith (9%/8%), alcohol (8%/7%), aquatherapy (5%/6%), illicit drugs (4%/2%), acupuncture (2%/1%), hypnosis (2%/1%), and biofeedback (1%/1%).

Conclusions:

Initial data corroborate the high prevalence of pain and functional disability in adults with hemophilia and highlight opportunities to address clinical assessment, patient dialogue, and management strategies to improve outcomes.