There is currently no consensus on optimal prophylaxis with clotting factor concentrates in hemophilia A. With or without pharmacokinetic data, prophylaxis regimens are often based on local practice and patient-specific factors, including bleeding history and activity level. The PREDICT study evaluated a baseline clinical risk score, based on phenotypic and biologic variables, to guide prophylactic regimen selection when switching from standard half-life (SHL) factor VIII concentrates to damoctocog alfa pegol. This multicenter, prospective study enrolled 21 participants aged ≥ 12 years with congenital hemophilia A of any severity who had received SHL prophylaxis for ≥ 6 months. Each participant was assigned a risk score (low, medium, high) based on five predefined variables: bleeding phenotype, treatment frequency, active target joints, von Willebrand factor levels, and physical activity. All participants initiated damoctocog alfa pegol at twice-weekly dosing for 4 weeks, after which regimens were individualized: 2×/week for high risk, every 5 days (Q5D) for medium risk, and Q5D for 4 weeks followed by less frequent dosing for low risk participants. A favorable outcome was defined as a reduction in annualized bleeding rate (ABR) and/or infusion frequency compared with previous SHL prophylaxis. Among 17 evaluable participants, 12 (70.6

OBJECTIVES:To assess the effectiveness and safety of damoctocog alfa pegol in patients with severe and nonsevere hemophilia A in the fifth interim analysis of the ongoing HEM-POWR study. METHODS:HEM-POWR (NCT03932201) is a multinational, Phase 4, prospective observational study. The key objectives were the annualized bleeding rate (ABR) and adverse events. RESULTS:At data cutoff (July 8, 2024), the safety analysis set and full analysis set (FAS) included 370 and 270 patients, respectively. In the modified FAS (patients with ≥ 90 days of bleed data), the mean (standard deviation; SD) ABR for total bleeds was 2.8 (5.9) 12 months prior to damoctocog alfa pegol initiation with the previous FVIII product and 2.1 (4.8) during the observation period. Bleed protection with damoctocog alfa pegol was maintained across disease severity, age group, BMI group, dosing regimen, and patient inhibitor history. One patient died due to spinal cord ischemia unrelated to the study drug. One patient developed a transient low-titer inhibitor, which resolved without clinical consequence. CONCLUSIONS:This updated analysis further demonstrated the effectiveness, acceptable safety profile, and tolerability of damoctocog alfa pegol for previously treated patients with severe and nonsevere hemophilia A from adolescence to older age in a real-world setting.

BACKGROUND:Hereditary factor X deficiency (HFXD) is an ultra-rare, autosomal recessive bleeding disorder that results in reduced factor X coagulant activity (FX:C). HFXD is traditionally classified by severity as severe (FX:C <1%), moderate (FX:C = 1%-5%), or mild (FX:C = 6%-10%). Treatment aims to replace the deficient factors, but there are no standardized guidelines for management. STUDY DESIGN AND METHODS:This multicenter retrospective chart review examined the diagnostic features, bleeding patterns, and current management strategies for HFXD patients in the United States. Patients were classified based on the revised European Network of Rare Bleeding Disorders (EN-RBD) criteria: severe (FX:C <10%), moderate (FX:C = 10%-40%), and mild (FX:C >40%). Data, including demographics, bleeding symptoms, laboratory analyses, and treatments, were collected. RESULTS:Twenty-four patients were included, with diagnoses based on family history or significant bleeding history; most were diagnosed in childhood (n = 10) or adolescence (n = 6). All patients had FX:C >5%, with 2 and 12 patients classified as EN-RBD mild and moderate, respectively. Twenty patients experienced bleeding episodes requiring treatment. Bleeding episodes were heterogeneous, ranging from epistaxis to spontaneous subdural hematoma; treatments included antifibrinolytics, hormonal therapy, and factor replacement. Seven patients with FX:C >40% had bleeding episodes that required treatment, and 3 of them experienced multiple bleeding episodes. DISCUSSION:HFXD presents with variable bleeding phenotypes that may not correlate with FX:C levels. This analysis demonstrates that while bleeding phenotypes generally align with the revised EN-RBD classification, patients with mild or moderate HFXD can experience significant bleeding. Future work should focus on correlating genotype with phenotype and refining management guidelines for mild and moderate HFXD.

The treatment landscape for hemophilia has evolved rapidly over the past decade, with the approval of several therapies with novel mechanisms of action. Extended half-life factor concentrates and nonfactor therapies, including factor VIII mimetics and rebalancing agents, have reduced treatment burden while also improving bleed protection. Although these new therapies provide an unprecedented ability to personalize treatment and to meet changing needs across the life span for each individual, the complexity of these treatment considerations has made clinical decision-making and selection of the optimal treatment challenging for those living with hemophilia and their clinicians.

Introduction: Damoctocog alfa pegol (BAY 94-9027) is an extended half-life recombinant replacement factor VIII (FVIII) product for use in previously treated patients aged ≥12 years with hemophilia A. Previous interim analyses of the HEM-POWR study demonstrated effectiveness and safety of damoctocog alfa pegol. There are age-related considerations in the management of hemophilia. Adolescents may want to pursue a more active lifestyle and play sports as well as coping with transition to independent treatment. An aging population of patients with hemophilia A means that treatment is being managed alongside age-related comorbidities. Additionally, older and younger patients may be underrepresented in clinical trials. This subgroup analysis presents updated data from the fourth interim analysis of HEM-POWR specifically for these age groups of interest, ie, adolescent patients aged ≥12 to <18 years and older patients aged ≥60 years. Methods : HEM-POWR (NCT03932201) is an ongoing, phase 4, observational, multicenter, and multinational study. The primary endpoint is annualized bleeding rate (ABR) and is assessed in the full analysis set (FAS); secondary endpoints include safety and are assessed in the safety analysis set (SAF). The FAS includes all eligible previously treated patients with bleeding data who received ≥1 documented dose of the study drug in the patient diary. The SAF consists of previously treated patients who received ≥1 dose of study drug during the observation period. Results: At data cutoff (1 August 2023), overall, there were227 patients included in the FAS and 332 in the SAF. Total median (Q1, Q3) observation period overall was 728.0 (491.0, 876.0) days in the FAS and 624.0 (364.5, 822.5) in the SAF. In the FAS, 33/227 (14.5%) had nonsevere and 190/227 (83.7%) had severe disease (data missing for 4 patients). Of all patients in the FAS,17 were aged ≥12 to <18 years and 21 were aged ≥60 years and have been included in this subgroup analysis. All adolescent and 20/21 (95.2%) older patients were male. There were 3/17 (17.6%) adolescents and 1/21 (4.8%) older patients with a history of inhibitors. Most adolescents did not have a concomitant disease, the most common concomitant disease for older patients was hypertension (n=16, 76.2%). The most common regimen for previous FVIII product prior to damoctocog alfa pegol was every 2 days for adolescents (n=11, 64.7%) and twice weekly for older patients (n=7, 33.3%). At baseline, the most common prophylaxis regimen was twice weekly for adolescents (8/16, 50.0%) and older patients (12/19, 63.2%). Mean (standard deviation [SD])/median (Q1, Q3) ABR for total bleeds in adolescents prior to damoctocog alfa pegol initiation was 2.2 (3.2)/1.0 (0.0, 4.0); during the observation period, ABR was 1.1 (2.2)/0.0 (0.0, 0.8). For this adolescent subgroup, mean (SD)/median (Q1, Q3) difference in ABR from 12 months prior to damoctocog alfa pegol initiation to the observation period was -0.8 (1.7)/0.0 (-1.0, 0.0) for spontaneous bleeds, -1.2 (3.1)/0.0 (-1.0, 0.0) for joint bleeds, and -0.9 (2.1)/0.0 (0.0, 0.0) for spontaneous joint bleeds. Mean (SD)/median (Q1, Q3) ABR for total bleeds in patients aged ≥60 years prior to damoctocog alfa pegol initiation was 2.0 (3.5)/0.0 (0.0, 2.0); during the observation period ABR was 0.8 (1.1)/0.5 (0.0, 1.2) (data missing for 1 patient in the observation period). By bleed type, mean (SD)/median (Q1, Q3) difference in ABR for older patients was -1.0 (2.6)/0.0 (-1.5, 0.0) for spontaneous bleeds, -1.0 (2.4)/0.0 (-1.0, 0.0) for joint bleeds, and -0.8 (2.3)/0.0 (-0.5, 0.0) for spontaneous joint bleeds. In the SAF, 2 adolescents (6.7%) reported serious treatment emergent adverse events (TEAEs), including traumatic cerebral hemorrhage, epileptic absence, and hematuria. In the older subgroup, 3 (9.7%) reported serious TEAEs, including transurethral prostatectomy, rotator cuff syndrome, and injury. There were no deaths, new inhibitors, or study-drug related TEAEs reported in these subgroups. Conclusions : Results of this analysis demonstrate the consistent effectiveness and acceptable benefit-risk profile of prophylactic damoctocog alfa pegolin patients with hemophilia A regardless of age and challenges associated with this, such as activity level and comorbidities.These findings can inform routine clinical use of damoctocog alfa pegol in adolescent and older patients. Funded by Bayer.

Damoctocog alfa pegol (BAY 94-9027, Jivi®), is a site-specifically PEGylated, extended half-life recombinant factor VIII (FVIII) that is approved in several European and non-European countries for on-demand treatment and prophylaxis of bleeding in previously treated patients aged ≥ 12 years with hemophilia A. Reliable measurements can be obtained using most one-stage and chromogenic FVIII assays over a wide concentration range. The efficacy, safety and pharmacokinetics (PK) of damoctocog alfa pegol have been studied extensively in the PROTECT VIII clinical trials, and its long-term safety and effectiveness profile is continuing to build through observational and interventional real-world studies. The PK of damoctocog alfa pegol was shown to be improved as compared with that of sucrose-formulated rFVIII (rFVIII-FS, Kogenate®), and was also demonstrated to be non-inferior to and, for some variables, more favorable than rFVIII-Fc fusion protein, efmoroctocog alfa (Elocta®; NCT03364998), rurioctocog alfa pegol (BAX 855, Adynovate®/Adynovi®; NCT04015492), and antihemophilic factor (recombinant) plasma/albumin-free method (rAHF-PFM, Advate®; NCT02483208). Damoctocog alfa pegol was generally well tolerated and none of the patients in any of the clinical trials, including the PROTECT VIII clinical program, HEM-POWR, or ongoing single-center studies, developed FVIII inhibitors. Efficacy for perioperative hemostasis has been demonstrated. Low bleeding rates were achieved across the studies, with twice weekly, every 5-day and every 7-day prophylaxis offering patients ≥ 12 years and their clinicians the chance to tailor treatment to individual needs and lifestyles, while maintaining long-term protection from bleeds and their consequences.

Background The standard-of-care for hemophilia A (HA) involves prophylaxis (PPX) with factor replacement therapies (standard half-life [SHL] and extended half-life [EHL]), or emicizumab (Emi). Despite the availability of these therapies, the clinical burden of HA remains high due to breakthrough bleeding, joint damage, and consequent pain. Aim This study aimed to better characterize the usage of additional factor treatment beyond PPX for preventive use before physical activity and for the treatment of patient-reported bleeds in patients with HA (PwHA) treated with SHL, EHL, or Emi. Methods This was a retrospective, observational, cohort analysis of moderate to severe PwHA identified through the PicnicHealth database from the US, using electronic health record data linked to electronic patient-reported outcome data. Adult (≥18 years) and pediatric (0−17 years) patients with diagnosis of moderate (1%−5% endogenous FVIII) or severe HA (<1% endogenous FVIII) on routine PPX regimen between March 2022 and March 2024 were included. Patients with evidence of mild HA (6%−50%), any FVIII inhibitor (on index), or treated with efanesoctocog alfa were excluded. Demographic and clinical characteristics, additional factor treatment patterns and usage beyond PPX (to treat a bleed, before physical activity, before a procedure), patient-reported bleeding events (total bleeds, bleeds by treatment type, bleed causes [injury, spontaneous, procedure], and type [joint, muscle/soft tissue, etc.]), annualized bleed rates (ABRs), routine PPX product class exposure (SHL, EHL, and Emi) were assessed and reported descriptively. Additional factor treatment use did not exclusively mean bleed treatment in this study. Results In total, 131 PwHA were included with mean (SD) age of 29 (14) years, 76% were adults, 99% were males, and 87% had severe HA. Patients completed a median (IQR) number of 46 (31−51) Bleeds and Medication surveys during the study period (biweekly). For all patients, median (IQR) study duration (earliest-latest survey) was 1.89 (1.19−1.95) years (SHL PPX: 1.63 [1.04−1.95]; EHL PPX: 1.35 [0.87−1.94]; Emi PPX: 1.83 [1.10−1.95] years). Of all patients, 78% reported use of factor treatment in addition to PPX at least once during the study period (SHL PPX: 95%, EHL PPX: 83%, and Emi PPX: 65%). Most common reason was ‘to treat a bleed’ (76%), followed by ‘before, during, or after a procedure’ (25%), and ‘before physical exercise’ (21%) to prevent bleeding. Patients on SHL and EHL PPX tend to use the same product class for additional factor treatment (84% and 96%, respectively). Each patient had completed at least one survey where they reported zero bleeds (during the study period). Around 75% of patients reported one bleed, while 21% reported two bleeds in a single survey. Median (IQR) ABR for all patients, SHL, EHL, and Emi PPX users were 2.0 (0.8−5.6), 3.6 (1.0−7.1), 3.3 (1.2−10.7), and 1.4 (0.0−3.7), respectively. The majority of bleeds were treated (93.4% overall) using additional factor products beyond PPX (SHL PPX: 95.2%; EHL PPX: 96.4%; Emi PPX: 87.2%) with injection or other bleeding medications being most common treatment strategy (89.5% of all bleeds). Emi users were more likely to leave a bleed untreated followed by SHL and EHL PPX users (12.8%, 4.8%, and 3.6%, respectively). Causes of bleeding were majorly attributed to injury/ trauma (53.9% [SHL PPX: 55.4%; EHL PPX: 47.9%; Emi PPX: 59.5%]) followed by spontaneous bleed (43.7% [SHL PPX: 43.2%; EHL PPX: 50%; Emi PPX: 36.2%]). Procedural bleeds were rarely reported (2.4%). Approximately, 61% of overall bleeds were joint bleeds (SHL PPX: 69.8%; EHL PPX: 60.0%; Emi PPX: 50.2%). Muscle/soft tissue bleeds (31%) were also common (SHL PPX: 26.3%; EHL PPX: 31.5%; Emi PPX: 37.0%). All patients (100%) on SHL >3 times/week (x/wk) regimen used additional factor treatments compared to 94% on ≤3 x/wk regimen. Most patients (88%) on EHL >2 x/wk regimen used additional factor treatments compared to on ≤2 x/wk regimen (77%). Among Emi PPX users, 62% on weekly regimen, 64% on biweekly regimen, and 36% on monthly regimen used additional factor treatment. Conclusion The majority of patients with moderate or severe HA on routine PPX use additional factor treatments to treat bleeds, whereas a smaller proportion of patients use additional factor treatment before physical activity or procedures to prevent bleeds.

Management of bleeding in persons with hemophilia and inhibitors involves treatment with bypassing agents including recombinant activated factor VII (rFVIIa). Two rFVIIa products are commercially approved for use in the United States and the European Union. Eptacog alfa and eptacog beta share the same amino acid sequence but differ in posttranslational modifications. While rFVIIa has been used to manage bleeding in hemophilia patients with inhibitors for over 30 years, understanding of its mechanisms of action continues to evolve. In vitro and in vivo studies have suggested that rFVIIa could promote hemostasis by: 1) increasing tissue factor (TF)-dependent activation of factor X (FX), 2) directly activating FX on the surface of activated platelets, and 3) downregulating protein C anticoagulant effects by binding endothelial protein C receptor (EPCR). Studies of rFVIIa and rFVIIa variants in murine models of hemophilia demonstrate that platelet-dependent activity is sufficient for hemostatic efficacy. Dosing levels required in clinical practice are most consistent with a platelet-dependent mechanism of action. However, in vivo models also suggest that pathways involving EPCR binding contribute to rFVIIa hemostatic activity. Eptacog beta displays increased platelet- and EPCR-dependent endothelial cell-binding compared to eptacog alfa. Thus, the relative contribution of these mechanisms to the overall hemostatic efficacy of eptacog alfa and eptacog beta may differ. Further research is required to assess the clinical relevance of these differences. A better understanding of the mechanisms by which rFVIIa promotes hemostasis in patients will provide insights when evaluating clinical outcomes of safety and efficacy for innovative bypassing therapies.

BACKGROUND:Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. OBJECTIVES:To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. METHODS:GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate, annualized FVIII utilization, FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Safety was assessed by adverse events (AEs). RESULTS:At week 156, 131 of 134 participants remained in the study; overall, 17 of 134 resumed prophylaxis. Mean annualized bleeding rate for treated bleeds decreased from 4.8 (SD, 6.5) bleeds/y at baseline to 0.8 (SD, 2.3; P < .0001) bleeds/y after prophylaxis (prophylaxis cessation to last follow-up) and 0.97 (SD, 3.48) bleeds/y during year 3. Annualized FVIII utilization decreased 96.8% from baseline after prophylaxis and 94.2% during year 3. At week 156, mean and median FVIII activity were 18.4 (SD, 30.8) and 8.3 IU/dL, respectively. FVIII activity decrease was lower between years 2 and 3 than between years 1 and 2. At the end of year 3, clinically meaningful improvements in the Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score were observed (mean change from baseline, 6.6; 95% CI, 4.24-8.87; P < .0001). Mild alanine aminotransferase elevations remained the most common AE during year 3 (23.7% of participants). A serious AE of B-cell acute lymphoblastic leukemia was considered unrelated to treatment. CONCLUSION:Hemostatic efficacy was maintained, and safety remained unchanged from previous years.

Objectives: To assess effectiveness and safety of damoctocog alfa pegol in interim analyses of the ongoing real-world hemophilia A HEM-POWR study.Methods: HEM-POWR (NCT03932201) is a multinational Phase 4 prospective observational study. The primary objective was annualized bleeding rate (ABR) in previously treated patients (PTPs) with hemophilia A. Secondary objectives included adverse events and number of affected joints.Results: At data cut-off (August 17, 2022), the safety analysis set included 268 patients and the full analysis set (FAS) included 161 patients. The most common dosing regimen during observation period was prophylaxis (FAS = 158/161, 98.1%) every 3-4 days (twice weekly; FAS = 78/158, 49.4%) and a median (min, max) infusion dose of 37.5 (10, 72) IU/kg. PTPs receiving prophylactic damoctocog alfa pegol have fewer infusions compared with prior treatment. Median total ABR (Q1, Q3) was 0.0 (0.0, 1.8) and mean total ABR (SD) was 2.4 (8.2). The proportion of patients with no affected joints increased between initial visit and follow-up. No FVIII inhibitors, treatment-related adverse events, or deaths were reported.Conclusions: Damoctocog alfa pegol shows effectiveness and acceptable safety, as well as consistent utilization, in real-world PTPs with hemophilia A, including in patients with non-severe hemophilia and those with a history of inhibitors. Please see video for a summary of this study.

Patients with haemophilia (PWH) have not been spared from the obesity epidemic. The reported prevalence of overweight (BMI 25–29.9 kg/m2) and obese (BMI ≥ 30 kg/m2) adults in the US haemophilia population is 19%−59% and 18%−36%, respectively.1, 2 While the impact of obesity on the general population is well-known, its effect on adult PWH is not well-studied. Past work has suggested obesity is associated with increased loss of joint mobility in PWH.3 We sought to more fully characterize the impact of obesity on PWH using the ATHN dataset, a large multicentre registry of data from 146 participating haemophilia treatment centres (HTCs) supported by the American Thrombosis and Haemostasis Network. Using this database, we evaluated the association between obesity, adverse joint outcomes (need for joint surgeries), and chronic pain. As pain medication use was not well recorded in the ATHN dataset at the time of our review, we performed a retrospective chart review of electronic health record (EHR) data of two centres in the ATHN dataset to assess the impact of obesity on chronic pain medication use. We hypothesized that patients above normal body weight would have a higher incidence of joint surgeries and chronic pain. We identified all adult patients (age ≥ 18 years) with haemophilia A or haemophilia B enrolled in the ATHN dataset from 2012 to 2017.4 We extracted multiple demographic and clinical variables in addition to body mass index (BMI) at each encounter during the study period. We excluded patients who were underweight (BMI < 18.5 kg/m2) upon entry into the cohort as well as outliers of BMI that were clearly reporting errors. We initially planned to assess joint bleeding as an outcome, but there was a significant amount of missing data. We assessed if a joint surgery or procedure (joint replacement, arthroscopic joint procedure, synovectomy (open, radioscopic, and/or radionuclide)) occurred during the study period. If BMI was missing for an encounter during which joint surgery occurred, BMI was imputed using the most frequent BMI category for a specific subject. BMI and joint surgery status (yes/no) could change over time for each patient during the period of interest (repeated measures). Thus, we used a generalized estimation equation methodology to estimate the odds of having joint surgery based on race, primary diagnosis, severity of haemophilia, current or former history of an inhibitor, HCV, and HIV. For the primary GEE model, we categorized BMI as >25 kg/m2 versus ≤25 kg/m2. We then performed sensitivity analysis with BMI in quartiles as well as BMI categories (normal, overweight, and obese). As pain medications were not frequently recorded in ATHN,5 we performed a retrospective review of electronic health record (EHR) data at two adult haemophilia treatment centres (University of Pennsylvania and University of Minnesota) between June 2015 and June 2019 in patients with haemophilia A or haemophilia B of any severity. We excluded underweight patients (BMI < 18.5 kg/m2) and patients missing BMI. We extracted demographics, clinical features, BMI, and pain medication use (opioid or non-opioid) at the two centres. Chronic pain medication (opioid or non-opioid) use was defined as a prescription for opioid for three or more consecutive months during the study period. As non-opioid pain medication use can be obtained over the counter and may not be accurately recorded in the EHR, we chose the use of chronic opioids as our primary outcome. We compared clinical features and chronic pain medication use between BMI categories using a Fisher exact test. We then performed multivariable logistic regression to determine an association between BMI category (i.e., normal [18.5–24.9 kg/m2], overweight [25–29.9 kg/m2], obese [≥30 kg/m2]) and need for chronic opioid pain medications. This study was determined to be exempt by the Institutional Review Board at the University of Pennsylvania. In the ATHN dataset, we identified 1639 PWH, 1215 (74.1%) with haemophilia A and 424 (25.9%) with haemophilia B (Appendix 1A). In this cohort, 22.3% of patients had mild, 20.2% moderate, and 57.4% severe haemophilia; .2% were of unknown severity. A total of 1039 (63.4%) PWH had a BMI > 25 kg/m2 (34.2% had a BMI 25−29.9 kg/m2; 29.2% had a BMI > 30 kg/m2). The mean first BMI measurement in this cohort was 27.8 kg/m2 (std dev 6.1 kg/m2). Of PWH, 14.4% had a current or former history of an inhibitor. There were 9077 encounters during the study period in 1639 patients. During the study period, 10.80% (177/1639) of all PWH had at least one joint surgery/procedure recorded (228 total joint surgeries/procedures). The type of joint surgery was arthrodesis in 4.8%, arthroplasty in 53.5%, arthroscopy in 30.7%, radionuclide synovectomy in 7.0%, and synovectomy in 4%. Of the joint surgeries, 34.5% (n = 61) were performed in patients with a normal BMI, 37.3% (n = 66) in overweight patients, and 28.2% (n = 50) in obese patients. In the adjusted model, BMI > 25 kg/m2 was not associated with increased odds of joint surgery (Table 1). GEE models with different BMI categories (BMI quartiles or normal, overweight, obese categories) showed consistent results as BMI categorized as >25 and <= 25 kg/m2. For every 10-year increment in age, the odds ratio of having joint surgery increased by 22%. The odds ratio of having joint surgery was 4- and 3-fold higher in patients with severe and moderate haemophilia, respectively, compared to patients with mild haemophilia. A current or former inhibitor history increased the likelihood of a joint surgery/procedure by 65%. In our two-centre analysis of EHR data, we identified 210 PWH (77.9% haemophilia A and 22.1% haemophilia B) at the University of Pennsylvania and 183 PWH (81% haemophilia A and 19% haemophilia B) at the University of Minnesota (Appendix 1B). Seven patients were excluded for underweight BMI and one for missing BMI. The incidence of moderate or severe haemophilia was similar between institutions, with 17.9% moderate and 52.5% severe at the University of Pennsylvania, and 16.1% moderate and 51.7% severe at the University of Minnesota. Combining data from the two HTCs, 36.9% of PWH were overweight and 31.7% were obese. There was no significant correlation between severity of haemophilia (mild, moderate, severe) and BMI category (p = .561) or between presence of haemophilic arthropathy and BMI category (p = .408) (Table 2). Of the haemophilia patients studied, 47.5% required chronic pain medications with 16% requiring opioids. In the multivariable analysis, adjusted for moderate or severe haemophilia, prophylaxis use, presence of an inhibitor, age, presence of haemophilic arthropathy, the overweight or obese BMI (BMI ≥ 25 kg/m2) compared to normal BMI group (BMI < 25 kg/m2) was not significantly associated with chronic opioid pain medication use [OR 0.61 (95% CI 0.31–1.19)] (appendix 1C). Normal 18.5–24.9 kg/m2 N = 121 N (%) Overweight BMI 25−29.9 kg/m2 N = 142 N (%) Obese ≥30 kg/m2 N = 122 N (%) In this retrospective analysis of a large dataset of PWH, we did not find an association of overweight/obesity with an increased need for joint surgeries. In our two-centre EHR review, we also did not find a correlation between overweight or obese BMI status and chronic opioid or non-opioid pain medication use. Past studies are inconsistent regarding whether obesity is a risk factor for joint surgeries/procedures. Similar to our study, a prior multicentre analysis of the Universal Data Collection (UDC) database from 2000 to 2010 did not identify overweight/obese status as a risk factor for joint procedures (specifically joint synovectomy) in PWH.6 However, the study found that overweight status (but not obesity) was a risk factor for joint arthrodesis compared to normal BMI.6 A Taiwanese study also found an association between obesity and annualized joint bleeding rates but did not report the incidence of joint surgeries/procedures.7 Our study found that 16% of PWH were prescribed an opioid pain medication. One of the centres in our study, the University of Minnesota, previously published a high incidence of opioid use in adult and adolescent PWH. This observation was consistent with the pooled findings in our current study.5 A recent meta-analysis reported a pooled incidence of chronic pain in 46% of all PWH, and in 53% of patients with severe hemophilia.8 While our current study did not find an association with overweight/obese status and chronic opioid use, it provides further evidence that chronic pain is a prevalent issue in PWH. Further studies assessing risk factors are needed. Our study was limited in that not all adverse joint outcomes (e.g., joint bleeds) and relevant clinical factors (e.g., factor usage) could be assessed using the ATHN dataset due to concerns for incompleteness of data. We chose joint surgeries/procedures as a primary outcome because it is a major event, which was likely to be accurately recorded in the dataset. Nevertheless, inaccurate reporting cannot be excluded as we did not have linking identifiers available to confirm by chart review that joint surgeries were appropriately recorded in ATHN dataset. There were insufficient joint surgeries performed at our centre to be able to validate this outcome with one centre. Furthermore, joint surgeries prior to the study period were not recorded, which may have resulted in misclassification of patients who had joint surgery prior to 2012. It is likely that some of the risk factors for joint surgery, particularly haemophilic arthropathy, are underreported in this study as we relied on clinical documentation in the electronic health record. There are also patient-specific factors apart from chronic pain that may influence a patient's likelihood of undergoing joint surgery such as access to healthcare and economic status. In addition, providers may be less likely to recommend surgery in the presence of certain comorbidities including obesity. While historically HIV infection and/or viral hepatitis may have been viewed as a contraindication to joint surgery, neither of these infections was associated with a decreased likelihood of joint surgery in our study. A strength of our study was supplementing the ATHN dataset with an EHR review at two participating HTCs to obtain information on pain management. Assessing the role of obesity as a risk factor for chronic pain may lead to targeting weight loss as an intervention for affected patients. Future studies that include quality of life, functional status, factor use, and healthcare utilization are needed to fully assess the impact of obesity on PWH. Allyson M. Pishko, Adam Cuker and Keerthy Joseph designed the research study. Allyson M. Pishko, Keerthy Joseph and Skye Peltier performed the research. Dunlei Cheng and Xiaoyan Han analysed the data. Allyson M. Pishko, Adam Cuker and Keerthy Joseph drafted the manuscript. Mark T. Reding critically reviewed the manuscript. All authors approved of the final manuscript. This work was supported by a 2019 HTRS Mentored Research Award supported by Sanofi Genzyme and the Eastern Pennsylvania Chapter of the National Hemophilia Foundation granted to Allyson Pishko. Adam Cuker has served as a consultant for Synergy; has received authorship royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, Spark, and Takeda. Skye Peltier has served on advisory boards for Novo Nordisk, Sanofi Genzyme, and Sigilon Therapeutics; she has also served as a speaker for Novo Nordisk. MR has served on advisory boards and/or speakers bureaus for Bayer, BioMarin, CSL Behring, HEMABiologics, Novo Nordisk, Sanofi, and Takeda; his institution has received research support from Bayer and Biomarin. Allyson M. Pishko receives research funding from Sanofi Genzyme, and served on an advisory board for BioMarin. HTRS Mentored Research, Sanofi Genzyme and the Eastern Pennsylvania, National Hemophilia Foundation. This study was determined to be exempt by the University of Pennsylvania IRB. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.