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Background: Depression and anxiety are associated with poor health-related quality of life (HRQoL), lower functioning and decreased treatment adherence. In 2019, 7% adults in the US had moderate/severe symptoms of depression, while Disclosures Roberts: Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy; Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding. Kulkarni: Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sidonio: Bayer: Consultancy; Catalyst: Consultancy; Genentech: Consultancy, Research Funding; Novo Nordisk: Consultancy; Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Biomarin: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding. Carpenter: Genentech: Honoraria; Novo Nordisk: Honoraria; Kedrion Pharmaceuticals: Honoraria; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Konkle: Pfizer, Sangamo, Sanofi, Sigilon, Spark, Takeda and Uniqure: Research Funding; BioMarin, Pfizer and Sigilon: Consultancy. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

Background: The Consensus Study report from National Academy of Science, Engineering, Medicine on September 2020 found a lack of data to characterize sickle cell disease (SCD) related disease burden, outcomes, and the unmet needs. This study’s objectives were to 1) assess the feasibility of collecting data to estimate illness burden in adults with SCD; 2) investigate factors associated with health-related quality of life (HRQoL); and 3) estimate the societal burden. Method: We recruited 32 adults aged ≥18 years with a diagnosis of SCD who obtained care at two adult SCD specialty centers in the US. We collected data on fatigue, HRQoL measured by the EQ-5D-3L and the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me), and the Work Productivity and Activity Impairment via patient survey. Healthcare utilization was abstracted for the 12 months prior to enrollment using medical chart review. Factors associated with HRQoL scores were assessed by Pearson correlations. Results: Data collection was feasible, although prescription data could not be used to estimate medication costs. Mean age was 36.7±10.6 (standard deviation) years, 84.4% had hemoglobin (Hb)SS/Sbthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D VAS was 63.4. The mean EQ-5D index score was 0.79. ASCQ-Me scores are comparable to the referent population of adults with SCD. The mean fatigue score was 57.9 (range 33.7-75.9) and was negatively correlated with the EQ-5D index score (correlation coefficient r=-0.35, p=0.049), and ASCQ-Me scores, including pain (r=-0.47, p=0.006), sleep (r=-0.38, p=0.03), and emotion (r=-0.79, pConclusions: Fatigue, SCD complications, hospitalization and chronic pain negatively impact HRQoL in this small cohort of US adults with SCD. This sample experienced a high economic burden, largely from outpatient doctor visits.

Introduction: Over the past 21 years, treatment options for hemophilia have evolved significantly. The objective of this study is to describe the trends observed in clinician prescribing practices for management of hemophilia A (HA) and B (HB) in the United States (US) via three surveys from 1999-2021. Methods: We administered surveys to members of the Hemostasis & Thrombosis Research Society (HTRS) via an in-person paper survey at its annual symposia in 1999 and 2015, and an online survey in 2021. The survey participants included physicians, physician assistants, and nurse practitioners who manage the care of hemophilia patients at hemophilia treatment centers in the US. The surveys collected information regarding: 1) characteristics of clinician practice, 2) prescribed clotting factor products and dosages used for routine bleeds or major life-threatening bleeding, total joint replacement, and port placement, 3) reasons for changing doses, 4) frequency of recommendation for prophylaxis and inhibitor treatment for associated factor and non-factor products, and 5) gene therapy. Results: Forty-one clinicians completed the survey in 1999 and 2021, 53 in 2015. The mean number of patients seen by respondents increased from 142 (range: 0-314) for children and 101 (0-480) for adults in 1999 to 202 (0-900) for children and 154 (0-500) for adults in 2021. The proportion of clinicians prescribing >40 units/kg of Standard Half Life (SHL) Factor IX concentrates for routine bleeding events in HB patients increased from 22.5% in 1999 to 50.9% in 2015, and 87.8% in 2021. The proportion of clinicians reported SHL Factor VIII usage for routine bleeding at a dose of >40 units/kg in HA patients increased from none in 1999 to 11.3% in 2015 and 29.3 % in 2021. The reported rates of prescribing an average >60 units/kg factor to treat major life-threatening bleeds increased from 67.5% in 1999 to 90.3% in 2021 for HB; rates were 2.5% in 1999, 17.3% in 2015 and 7.3% in 2021 for treating HA. For children 91% of clinicians reported prescribing emicizumab to treat HA inhibitors in patients of all ages, while >87% reported prescribing it to treat HA without inhibitor. Clinicians were more likely to always prescribe emicizumab to treat HA patients with inhibitors (63.2% for children and 57.1% for adults), as compared to always prescribing it for those without inhibitors (13.2% for children and 5.7% for adults). The most frequent reported method to treat a patient with a history of inhibitors on emicizumab who had break through bleeds was rFVIIa: 85.4% for children, and 75.6% for adults. The most frequently reported reasons for switching from FVIII to emicizumab were fewer injections/visits (87.8%), and improved patient quality of life (82.9%). Thirty-nine percent of clinicians reported caring for patients currently in gene therapy trials, 27.5% had patients who had completed gene therapy. When asked about potential future prescribing practices, 14.6% reported that they would prescribe gene therapy "all the time", 4.9% would prescribe it "about 3/4 of the time", 29.3% "about 1/2 the time", 29.3% "about 1/4 the time", and 22.0% "rarely or never". Conclusion: These data indicate changes in prescribing practices among hemophilia specialists in the US over the past 21 years. Prescribing of high doses of factor (>40 units/kg) increased, while ITI prescribing practices remained similar over time. To treat patients with major life-threatening bleeds, a larger proportion of clinicians prescribed high doses of factor (>60 units/kg) for patients with HB as compared to HA. Most clinicians frequently prescribed emicizumab for patients with HA inhibitors, but less frequently for those without inhibitors. At this time, there is wide diversity among clinicians in the expected uptake of gene therapy. Disclosures Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. Decker-Palmer: Genentech Inc. --A member of the Roche Group.: Current Employment, Current equity holder in publicly-traded company. Khairnar: Genentech Inc - A Member of The Roche Group: Current Employment; University of Maryland, Baltimore: Ended employment in the past 24 months; Roche: Current equity holder in publicly-traded company. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

Introduction: Persons with hemophilia suffer from recurrent bleeds, especially hemarthrosis, which results in joint damage. Hemophilia inhibitor status impacts bleeding, which is associated with acute and chronic pain. To better characterize the impact of inhibitor status, we compared patient-reported outcomes (bleed rate, pain, and joint health), work productivity and activity impairment (WPAI), and health-related quality of life (HRQoL) by inhibitor status, and investigated the correlation of patient-reported outcomes with WPAI and HRQoL. Methods: The U.S. Hematology Utilization Group Studies Part VIII prospectively collected data to examine the cost and burden of hemophilia in persons with hemophilia A (PwHA) aged ≥2 years obtaining care at four federally-supported hemophilia treatment centers. From April 2019 to May 2021 we enrolled PwHA with and without inhibitors at a 1:2 ratio. Parents/adult participants completed a survey at enrollment to collect sociodemographic and clinical characteristics, self-reported bleeds in the last month, pain, and joint stiffness (5-item scale). We also measured WPAI and HRQoL using EQ-5D-3L. Clinical chart review documented hemophilic severity, inhibitor level and treatment regimen. Participants were classified into three groups: 1) active inhibitor (inhibitor titer ≥1.0 Bethesda Units (BU) six months prior to enrollment), 2) tolerized inhibitor (history of inhibitor titer ≥1.0 BU, immune tolerance induction (ITI) and/or currently using factor VIII for prophylaxis), and 3) no inhibitor. Patient-reported data were compared across these groups using Chi-square tests for categorical variables and generalized linear models for continuous variables. Association of bleeds, pain, and joint stiffness with HRQoL and WPAI were assessed using Pearson correlation. Results: Among 80 PwHA enrolled, 9 (11%) had active inhibitors, 22 (27.5%) had tolerized inhibitors, and 49 (61.3%) had no inhibitors. Mean age was 24.9±14.3 (standard deviation) years, 66.3% were adults, 87.5% had severe hemophilia, and 87.5% used prophylaxis. Mean age of the non-inhibitor group (29.3±13.5) was older than the tolerized inhibitor group (16.3±9.5 years, p0.05). The non-inhibitor group had a lower rate of severe hemophilia (81.6%) or prophylactic treatment (81.6%) than those in the active (100%) or tolerized groups (95.5%, p=0.13). Larger proportions of participants with active inhibitors (66.7%) and no inhibitors (57.1%) reported having bleeds in the last month compared to those with tolerized inhibitors (22.7%, p=0.01). Participants without inhibitors had a greater mean number of bleeding episodes (1.09±standard error (SE) 0.26 vs. 0.23±0.38, p=0.03), specifically joint bleeds (0.58±0.16 vs. 0.08±0.24, p=0.03,) than the tolerized group. Those with active inhibitors reported significantly higher mean joint stiffness scores (35.1±2.6 vs. 27.5±1.9, p=0.006) or more joint pain (77.8% vs. 54.5%, p=0.23) than the tolerized group. Mean EQ-5D index score was significantly lower in the active inhibitor group (0.79±SE (0.07) than in the tolerized group (0.96±0.05, p=0.03). Joint bleeding, chronic pain, and joint stiffness were negatively correlated with the EQ-5D visual analogue scale, and index scores (all correlation coefficients |r|>0.43, all p Conclusions: This study is limited to a small sample skewed toward a younger age in the tolerized inhibitor group. PwHA in the active and no inhibitor groups experienced greater clinical burden as measured by bleeds compared to the tolerized group. Those with active inhibitor displayed lower HRQoL scores than the tolerized inhibitor group. Bleeds, chronic pain and joint stiffness were inversely correlated with HRQoL, resulting in lower work productivity and activity. Figure 1 Figure 1. Disclosures Roberts: Takeda; Speakers Bureau: Novo Nordisk, Octapharma, Sanofi, Takeda.: Research Funding; Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, Takeda, uniQure: Consultancy. Khairnar: University of Maryland, Baltimore: Ended employment in the past 24 months; Roche: Current equity holder in publicly-traded company; Genentech Inc - A Member of The Roche Group: Current Employment. Decker-Palmer: Genentech Inc. --A member of the Roche Group.: Current Employment, Current equity holder in publicly-traded company. Curtis: Pfizer, Bayer, and Novo Nordisk: Consultancy; University of Southern California: Consultancy. Wu: Baxalta US Inc., Bannockburn, IL (a Takeda Company), CSL Behring L.L.C., Octapharma USA, Inc., Genentech Inc.: Research Funding. Nichol: Pfizer, Genentech Inc., Baxalta US Inc., Bannockburn, IL (a Takeda Company), Octapharma, CSL Behring, Global Blood Therapeutics, and Novo Nordisk: Research Funding.

Background: Non-severe hemophilia A and B account for 50% of patients with hemophilia, in which factor level does not consistently correlate with bleeding phenotype. Clinical decision-making in regards to timely prophylaxis initiation and tailored surgical management could be informed by a biomarker that is more predictive of bleeding phenotype. We hypothesized that a global method to assess clotting potential, such as thrombin generation (TG), is more predictive of bleeding phenotype than factor level. Objectives: Determine the ability of TG, as compared to standard baseline factor activity, to differentiate bleeding phenotype severity in patients with non-severe hemophilia. Methods: Subjects were recruited from two hemophilia treatment centers (HTCs): Rady Children's Hospital San Diego (RCHSD) and Center for Inherited Blood Disorders (CIBD). Subjects were eligible for enrollment if they were at least one year of age and had a diagnosis of non-severe congenital hemophilia A or B, or were genetically confirmed or suspected female carriers. All enrolled patients or their parents completed the standardized, self-administered pediatric bleeding questionnaire (Self-PBQ) or bleeding assessment tool (Self-BAT). Clinical and laboratory information were extracted from the medical chart, including age at diagnosis, bleeding event history, past surgical history, treatment history and factor VIII or IX gene analysis. Validation of self-reported bleeding symptoms was performed using chart-derived data. Bleeding phenotype was assessed using standard calculation of the bleeding score, as defined by the respective validated self-reported tools. For the purpose of this analysis, we defined a high bleeding score as 13 or more, while a low bleeding score was defined as 12 or less. After a washout period of 5x the standard half-life of the administered factor product, blood samples were collected at time of enrollment. Platelet poor plasma was obtained according to a strict protocol to minimize pre-analytical variables. TG was measured by means of the calibrated automated thrombogram, with three different reagents: low (1 pM of tissue factor [TF]), regular (5 pM of TF) and High (20 pM of TF). The following TG parameters were evaluated: Peak TG (Peak), estimated thrombin potential (ETP) and velocity index (VI). Results: Eighty-one subjects were enrolled. The median age of our cohort was 15.6 years (IQR 21.2, range 4.9 - 59.8), with a slight female predominance (51%) due to inclusion of female carriers. The median follow-up period at the HTC was 5.3 years (IQR 7.5 years), with the majority having follow-up for at least three years. Enrolled patients had the following diagnoses: mild hemophilia A (70%), mild hemophilia B (3%), moderate hemophilia A (13%), moderate hemophilia B (3%), hemophilia A carriers with normal factor VIII levels (10%) and hemophilia B carriers with normal factor IX levels (1%). Median age at diagnosis was 8 years (IQR 26.3, range 0.1 - 56.1), which strongly correlated lower baseline factor activity (r=0.573, p-value < 0.0001). The median baseline factor activity was 21% (IQR 26, range 2 - 249). Factor exposure occurred in 46% of patients (n=37), of which 5 patients were on prophylaxis at time of enrollment. Chronic arthropathy was present in 2 patients (one with mild hemophilia A and one with moderate hemophilia A) and none of the patients had a history of an inhibitor. The majority of patients had a low bleeding score (74% vs. 26%). Baseline factor level and TG values obtained with regular reagent (5 pM of TF) showed significant correlation with bleeding score (r = -0.229 to -0.237, p-value < 0.05), while values obtained with other reagents did not show a significant correlation. Sensitivity/specificity analysis revealed the following optimal cutoff values for differentiating between bleeding severities, as obtained from TG with regular reagent: ETP ( Conclusion: Even though both TG and baseline factor level had comparable correlation with bleeding severity, all TG values with 5 pM TF showed a much higher sensitivity outcome and greater ability to differentiate between bleeding severities in this population. This approach shows potential for predicting bleeding severity in patients with non-severe hemophilia and should be validated in long-term prospective studies. Disclosures Nossair: Novo Nordisk: Other: Conference - Haemophilia Acadamy; Novo Nordisk: Research Funding. Hwang:BPI: Consultancy; Bayer: Consultancy; Hema Biologics: Consultancy; Shire: Consultancy; Bioverativ: Other: PI in clinical research study. Thornburg:ATHN: Research Funding; Bayer Pharmaceuticals: Research Funding; Biomarin: Consultancy; CSL Behring: Research Funding; Bioverativ: Consultancy; Genentech: Speakers Bureau; Octapharma: Research Funding; NovoNordisk: Research Funding; Shire: Research Funding; Johns Hopkins All Children's Hospital: Research Funding; Bluebird Bio: Consultancy.