Hemophilia Joint Health Score Research Articles

Effectiveness of emicizumab in preventing bleeding events in severe and moderate hemophilia A: A single-center experience in Bangladesh.

Emicizumab is a monoclonal antibody that bridges activated factor IX (FIX) and factor X (FX) to replace the function of missing activated factor VIII (FVIII) in hemophilia A patients irrespective of FVIII inhibitor status. This study assessed the effectiveness of emicizumab in preventing bleeding episodes in patients with hemophilia A. This observational study included patients with moderate to severe hemophilia A who were undergoing episodic FVIII replacement therapy. The primary endpoint was the difference in annualized bleeding rates (ABR) and the secondary endpoint was the difference in Hemophilia Joint Health Score (HJHS) before and after emicizumab prophylaxis. A total of 30 male hemophilia patients were included, the mean age was 16.7 (SD: ±8.1) years, and most of them had moderate hemophilia A [63.3%]. Before prophylaxis, the median ABR was 48 (interquartile range [IQR]: 35-60), and 93.3% of patients had ABR greater than eight, whereas after prophylaxis the median ABR decreased significantly (median [IQR]: 0 [0.0-0.4], p<0.001), and 56.7% had zero bleeds. ABR was not significantly different in patient with and without FVIII inhibitors. The HJHS scores significantly improved after prophylaxis (10 vs. 2.5, p<0.001). The bleeding events were reduced significantly (23 vs. 0.0, p<0.001), and zero new target joints were reported after prophylaxis. Most of the patients [93.3%] did not face any serious adverse events after prophylaxis. Emicizumab prophylaxis was associated with a significantly lower rate of bleeding events among participants with hemophilia A, regardless of inhibitor status.

The effectiveness and safety of octocog alfa in patients with hemophilia A: up to 7-year follow-up of the real-world AHEAD international study.

Real-world data assessing treatment outcomes in patients with hemophilia A in routine clinical practice are limited. To evaluate the effectiveness and safety of octocog alfa in patients with moderate/severe hemophilia A receiving treatment in clinical practice. The international Antihemophilic Factor Hemophilia A Outcome Database study is an observational, noninterventional, prospective, multicenter study. This planned interim data read-out was conducted following 7 years of observation of patients receiving octocog alfa (cut-off, 30 June 2020). The primary endpoint was joint health status, assessed by the Gilbert Score. Secondary endpoints included annualized bleeding rates (ABRs), Hemophilia Joint Health Score (HJHS), health-related quality of life, consumption, and safety. This post hoc analysis stratified data by hemophilia severity at baseline [moderate, factor VIII (FVIII) 1-5%; severe, FVIII <1%]. Of the 711 patients in this analysis, 582 (82%) were receiving prophylaxis with octocog alfa at enrollment, and 498 (70%) had severe disease. Median Gilbert Scores were higher with on-demand therapy versus prophylaxis and scores were comparable in moderate and severe disease. In patients receiving prophylaxis, there was an improvement in HJHS Global Gait Score over 7 years of follow-up overall and in patients with severe disease. ABRs and annualized joint bleeding rates were low across all 7 years. An ABR of zero was reported in 34-56% of prophylaxis patients versus 20-40% in the on-demand group. ABRs were similar in severe and moderate disease. In total, 13/702 (1.9%) patients experienced 18 treatment-related adverse events. These data demonstrate the long-term effectiveness and safety of octocog alfa in patients with moderate and severe hemophilia A, especially in those receiving prophylaxis. The high number of patients receiving on-demand treatment experiencing zero bleeds could be due to selection bias within the study, with patients with less severe disease more likely to be receiving on-demand treatment. ClinicalTrials.gov: NCT02078427.

Emicizumab Prophylaxis in Patients with Severe Hemophilia A: Insights from A Resource Limited Country.

In this prospective study, severe HA patients were recruited from January 2022 to June 2023. Inhibitor positive and inhibitor negative patients with annual bleeding rate (ABR) 8 or greater and past histories of bleeding like intra-cranial, intra-abdominal, and pseudo-tumors were included. Emicizumab loading dose was 3 mg/kg in the first 4 weeks, and the maintenance dose was started at week 5 at 6 mg/kg/month. Patients' detailed bleeding history and demographics were recorded. The five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) was used to evaluate patients' HRQoL. Furthermore, Hemophilia Joint Health Score (HJHS) and Functional Independence score in Hemophilia (FISH) were applied for the assessment of joints at different time points. Results were analyzed by SPSS version 21. A total of 36 HA male patients with the mean age of 19.7 ± 14.42 years were recruited in the study; among them, 19 patients were inhibitor positive, while 17 were negative. Patients clinically presented with bleeding symptoms which included: hemarthrosis 95%, GI bleeding 13.8%, and bruises and gums bleeding 13.8%. Significant reduction was observed in the bleeding episodes after the therapeutic intervention, and joints assessment and Euro-Quality-of-life Visual Analog Scale showed a significant improvement in health after treatment. Similarly, there was a remarkable reduction in bleeding episodes and improved quality of life among HA patients. The ABR decreased from 53.6% episodes per year prior to treatment to 2.4% during Emicizumab therapy. Prior to initiating Emicizumab therapy, participants exhibited an average FISH score of 16 and HJHS score of 10, indicating moderate limitations due to joint-related issues. After treatment, the mean FISH score improved to 9 and HJHS score to 4 reflecting a substantial enhancement in participants' ability to perform daily activities (P < 0.057). Our results showed that HA patients on prophylactic treatment with Emicizumab were less restricted and had improved quality of life due to marked decrease in bleeding episodes which resulted in improved health and social lives. In addition, it was well tolerated, and no participant discontinued treatment because of adverse events.

Low-dose emicizumab prophylaxis in patients with severe hemophilia A: a retrospective study bringing new hope for our patients

BackgroundLow-dose emicizumab can potentially offer a cost-effective treatment option in persons with hemophilia A, especially in developing countries. ObjectivesTo compare the efficacy and safety of low-dose emicizumab with those on low-dose factor (F)VIII prophylaxis via chart review. MethodsAfter ethics approval, chart data of 2 groups of patients were reviewed: group 1 (low-dose emicizumab, n = 10; 3 mg/kg monthly without a loading dose) and group 2 (low-dose FVIII prophylaxis, n = 10; 10-20 IU/kg of FVIII concentrates twice a week). Outcomes were target joints, annual bleeding rate, annual joint bleeding rate, Hemophilia Joint Health Score, nonactivated thromboelastometry–rotational thromboelastometry clotting time, plasma emicizumab levels, and direct costs of treatment. ResultsAll outcome measures were significantly better in the low-dose emicizumab group than in the low-dose FVIII prophylaxis group. For nonactivated thromboelastometry–rotational thromboelastometry, median values after 6 months in the low-dose emicizumab group were comparable with values seen in patients with mild hemophilia, while the values in the low-dose FVIII prophylaxis group were similar to those of patients with moderate hemophilia. The direct cost of low-dose emicizumab was found to be approximately US $6000 and that for low-dose recombinant FVIII prophylaxis used in our study was US $6282 (the cost may range from US $3432 to $7920 depending on the type of factor) when compared to approximately US $15 000 for standard-dose emicizumab. ConclusionLow-dose emicizumab offers a cost-effective treatment option and can improve access in developing countries. These findings need to be confirmed in a larger and better-controlled study.

The Correlation of Muscle Mass and Walking Distance with Joint Health and Functional Status in Hemophilic Arthropathy Among People with Hemophilia a (PwHA)

Introduction: Hemophilic arthropathy resulting from repeat joint bleeding is a common complication for people with hemophilia (PWH), despite the current prophylaxis therapy. Monitoring the status of musculoskeletal health for PWH is necessary. Muscle plays a critical role in maintaining and promoting the joint health. Muscle atrophy is one of the key features of haemophilic arthropathy. Up to date, there are more studies focusing on joint health of PWH but few having attention on the impact of limbs muscles on joint status of PWH. Clinical assessments such as muscle circumference and manual muscle strength tests fail to detect subtle muscle changes. The study aimed to evaluate the ultrasound measurement of muscle thickness in people with hemophilia A (PwHA) and its correlation to joint health and functional impairments. Methods and Materials: In the observational cross-sectional study, 29 PwHA (median age 35 years; range 13-63) were enrolled, including 27 severe-type diseases on prophylaxis therapy and 2 moderate-type diseases on episodic treatment. Muscle thickness of quadriceps and medial gastrocnemius were measured by ultrasound. Joint health and functional capacity were assessed using Haemophilia Joint Health Score (HJHS), Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US), Haemophilia Quality of Life Questionnaire for Adults (Haemo-A-QoL), and Haemophilia Activities List (HAL). 6-Minute Walking Test (6MWT) for global functional evaluation. Results: At the time when the 29 patients receiving this survey of joint health, there were 28 on rFVIIIFc treatment for an average of 31.2 months (mean: 33.5, range 19.5－43), among whom 26 severe-type patients had rFVIIIFc prophylaxis and 2 moderate-type patients had on-demand therapy with rFVIIIFc. Only one severe-type patient had received non-rFVIIFc product prophylaxis for &amp;gt; 3 years. Totally 174 joints were examined. By correlation analysis, a significant correlation was found between both quadriceps and calf muscle thickness and the HJHS knee and ankle scores, respectively, with a negative correlation ( r= -0.45, p=0.015*, right quadriceps; r= -0.60, p&amp;lt;0.001***, left quadriceps; r= -0.39, p=0.039*, right calf; r= -0.58, p&amp;lt;0.001***, left calf). A significant correlation between muscle thickness and HEAD-US was observed between quadriceps muscle and knee score, with a negative correlation ( r= -0.56, p=0.017*, right quadriceps; r= -0.36, p=0.0048**, left quadriceps). Therefore, Quadriceps muscle thickness significantly correlated with HJHS knee, HEAD-US knee, and HAL. Calf muscle thickness significantly correlated with the HJHS ankle. After adjusted age and BMI, calf muscle thickness was significantly associated with the HJHS ankle. Muscle thickness was also observed to correlate with Haem-A-QoL and HAL. 6MWT was found to significantly correlated with HJHS total, HEAD-US total, Haem-A-QoL, and HAL ( r= -0.42, p=0.0231*, HJHS; r= -0.52, p=0.0037**, HEAD-US; r= -0.60, p&amp;lt;0.0001***, Haem-A-QoL; r= 0.64, p&amp;lt;0.001***, HAL). Conclusion: For the first time, limbs muscle thickness and the distance of 6MWT were linked to assessment of joint health, quality of life and activity participation in PwHA. Ultrasound measurement of muscle thickness appears to be a reliable tool for the assessment of muscle mass in PwHA.The 6MWT also appears to be useful tool for assessment of physical capacity and endurance in PwHA. Disclosures: No relevant conflicts of interest to declare.

Experience with Emicizumab Among People with Hemophilia A in the Canadian Hemophilia Bleeding Disorders Registry

Background: The use of emicizumab as prophylaxis to prevent bleeding or reduce the frequency of bleeding episodes in congenital hemophilia A (HA) was approved by Health Canada for the treatment of people living with HA (PwHA) with FVIII inhibitors in 2018, and without inhibitors in 2019. Here we present the results of a non-interventional, cohort study, using data routinely collected by the Canadian Bleeding Disorders Registry (CBDR) to evaluate treatment patterns of emicizumab in Canada and the associated safety and effectiveness outcomes, including quality of life. Methods: De-identified data were extracted from the CBDR database for all registered PwHA who had received emicizumab at least once prior to December 31, 2022. Baseline demographic characteristics were stratified by disease severity (defined by the level of endogenous FVIII activity) and age. Effectiveness outcomes were measured by the proportion of patients with zero, traumatic, spontaneous, or joint bleeds as well as annualized bleeding rates (ABR) for any treated bleed. Intra-patient comparisons of bleeding were performed for all patients and for those with at least six months follow-up in both pre- and post-emicizumab periods as a sensitivity analysis. Effectiveness outcomes also included patients' Hemophilia Joint Health Score (HJHS), Patient Reported Outcomes, Burdens and Experiences (PROBE), and EQ-5D index and visual analog scale (VAS) scores. We performed a complete data analysis, without imputation. This study was approved by the research ethics board of McMaster University and other participating centers, and abides by the guiding principles of the Declaration of Helsinki. Results: In total, 533 PwHA received at least one dose of emicizumab (PwHA E) in the CBDR database. Overall, 498 (93.4%) PwHA E had severe disease, 28 (5.3%) had moderate disease, and 7 (1.3%) had mild disease. At start of emicizumab exposure, 220 (41.3%) PwHA E were &amp;lt;18 years old; 78 (14.6%) PwHA E had current FVIII inhibitors, 82 (15.4%) had a history of FVIII inhibitors, and 373 (70%) had no history of inhibitors ( Table 1). A total of 13 adverse events were reported in the entire observation period, including one event of thrombosis (occurring in one person with COVID-19), seven allergic reactions, two FVIII Inhibitor development, two neurological events (headache; and headache, nausea, and vomiting) and one case of large hematoma developed at operative site following removal of port-a-cath. Moreover, nine COVID-19 cases were reported as adverse events. Over a median (first quartile, third quartile) follow-up time of 249 (136, 395) days, 388 (72.8%) PwHA E had no recorded bleeds. Out of 145 PwHA E with recorded bleeds, 106 had joint bleeds, 87 had traumatic bleeds, 69 had spontaneous bleeds and 46 had other bleeds (Table 2). An intra-patient comparison in all PwHA E (n=533) showed a decrease in mean (95% confidence interval [CI]) annualized bleeding rate (ABR) from 1.22 (1.06, 1.42), pre-emicizumab (2018, prior to first dose) to 0.50 (0.41, 0.60) post-emicizumab (rate ratio (95% CI) 0.41 (0.33, 0.50), p-value &amp;lt;0.001). The Intra-patient comparison in PwHA E without current inhibitor (n=455) showed a decrease in mean ABR (95% CI) from 1.02 (0.87, 1.19) to 0.54 (0.44, 0.66) (rate ratio (95% CI) 0.53 (0.43, 0.65), p-value &amp;lt;0.001). The Intra-patient comparison in PwHA E with current inhibitor (n=78) showed a decrease in mean ABR (95% CI) from 5.03 (3.30, 7.66) to 0.41 (0.26, 0.65) (rate ratio (95% CI) 0.08 (0.04, 0.15), p-value &amp;lt;0.001). Conclusions: This analysis describes the baseline characteristics, safety and effectiveness outcomes of Canadian PwHA treated with emicizumab before December 31, 2022. A total of 387 new patients were included in this analysis compared to the previous one (data cut: December 31, 2021, n=146). The data shows that 72.8% PwHA E had no recorded bleeds since they started emicizumab and that there was a substantial decrease in bleeds post-emicizumab in both PwHA with and without current FVIII inhibitor. The safety profile of emicizumab was consistent with previous reports. The CBDR allows for a longitudinal follow-up of the Canadian hemophilia A population, which can inform healthcare practitioners and regulatory authorities of the safety and efficacy outcomes of treatments in routine clinical practice.

Characterization of Joint Disease in Women with Hemophilia: The Carriers Ultrasound Project (CUP) Study

Introduction: Women with hemophilia (WWH) are at risk for bleeding despite normal or mildly reduced plasma factor VIII (FVIII) or IX (FIX) activity levels. Subclinical joint bleeds can contribute to longstanding and irreversible joint damage. Although joint health has been well-studied among men with hemophilia, there is currently a gap in knowledge on the prevalence, clinical characteristics, and natural history of joint health in women with hemophilia. No prior studies have utilized point-of-care musculoskeletal ultrasound (POC-MSKUS) to assess the presence and characteristics of joint changes in carrier women. Aim: This multi-institutional, cross-sectional study primarily aimed to evaluate and compare the prevalence and extent of joint-related symptoms and joint changes in WWH compared to age-matched controls utilizing validated clinical tools including the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol. We also aimed to examine the relationship between innate FVIII and FIX levels and presence of joint disease changes in this population. Methods: Between 2017-2023, women aged 18 to 40 years were enrolled and divided in 2 cohorts. The “carrier cohort” included women with a confirmed hemophilia A or B diagnosis, regardless of factor activity level. The “control cohort” included women without personal or family history of a bleeding disorder. Individuals were excluded if they had history of joint trauma or surgery within 12 months prior to enrollment or any history of joint replacement. Collected clinical information included presence of bleeding symptoms, joint-related symptoms, and historical use of hemostatic medications. Participants underwent clinical and radiological assessment of bilateral elbows, knees, and ankles using the Hemophilia Joint Health Score (HJHS) and HEAD-US protocol. Factor activity levels were measured in the carrier cohort. Descriptive and interferential statistics were performed using SPSS software with p&amp;lt;0.05 considered statistically significant. Results: Fifty-eight women, including 30 controls (51.7%) and 28 carriers (48.3%) were enrolled. The mean age at enrollment was 30.7 years (range: 19-39 years). Most women were White (79.3%) and Hispanic (51.7%). Of the 28 carriers, 85.6% (n=24) were hemophilia A carriers and 14.3% (n=4) hemophilia B carriers, respectively ( TABLE 1). Among carriers, the mean and median factor activity levels were 56% and 54% (range 20-120%) respectively. Carriers reported significantly higher prevalence of bleeding symptoms when compared to controls, including heavy menstrual bleeding (64.3% vs. 10%, p&amp;lt;0.001), epistaxis (25% vs. 3.3%, p=0.017), gingival bleeding (25% vs. 3.3%, p=0.017), and easy bruising (50% vs. 3.3%, p&amp;lt;0.001). The majority (53.5%, n=15) of carriers reported presence of joint-related symptoms when compared to controls, including joint pain (50% vs. 3.3%, p&amp;lt;0.001) and joint swelling (28.6% vs. 0%, p=0.02). Three (10.7%) carriers reported history of overt joint bleeds. Carriers had significantly higher mean HJHS scores (4.7 vs. 1.5, p&amp;lt;0.001) than did controls, however no significant changes in HEAD-US scores were found. A high body mass index (BMI) (&amp;gt;25kg/m2) was significantly associated with an increased prevalence of joint bleeding (25% vs. 0%, p=0.03) among carriers. When dividing carriers in 2 groups based on their baseline factor activity level (&amp;gt;40% versus &amp;lt;40%), the prevalence of bleeding manifestations and joint-related symptoms were similar ( TABLE 2). Carriers with factor levels &amp;lt;40% were more likely to require factor replacement on-demand (60% vs. 17.4%, p=0.046) and anti-fibrinolytics (60% vs. 17.4%, p=0.046) than carriers with factor levels &amp;gt;40%. There were no changes in mean HJHS or mean HEAD-US scores among the two groups. Conclusions: Women with hemophilia are at increased risk of bleeding manifestations and joint-related symptoms, regardless of factor activity levels. This population also seems to have poorer joint health than do non-carrier women as assessed by HJHS. Dedicated follow-up to help prevent and treat joint-related complications among WWH seems imperative. Our study did not detect significant ultrasonographic joint changes in the carrier cohort. However, joint findings may become more evident later in life or when assessed with magnetic resonance imaging. Further long-term studies are needed to support our hypothesis.

Sequential Use of Monthly Low Dose Emicizumab and Factor VIII Concentrate Prophylaxis Among Patients with Hemophilia a: A Case Series Report

Introduction: The effectiveness of monthly low dose emicizumab of 1.0 to 2.0 mg/kg has been reported among patients with and without inhibitor. However, their trough level of emicizumab was rather low ranging from 5.9 to 11.9 mg/mL and breakthrough bleeding episodes often occurred at the 4 th week after administering emicizumab. Moreover, non-exposure to factor VIII is one concern among patients receiving emicizumab prophylaxis. Therefore, the study aimed to evaluate the effectiveness of sequential use of monthly low dose emicizumab and factor VIII concentrate prophylaxis among patients with hemophilia A. Methods: Patients with hemophilia A without inhibitor were recruited. Sequential use of monthly low dose emicizumab in the first week and factor VIII concentrate in the 4 th week was provided. Patients were closely monitored concerning the number and sites of bleeding episode, cause of bleeding from spontaneous or trauma-related conditions and the amount of additional factor VIII concentrate to treat breakthrough bleeding episodes. Also, the comparison of quality of life, hemophilia joint health score (HJHS), hemophilia early arthropathy detection by ultrasound (HEAD-US) and ultrasonography of bilateral elbows, knees and ankles before and after prophylaxis was conducted. Results: Five male patients (4 adults, 1 boy) with hemophilia A (severe 2, moderate 3) without inhibitor were enrolled in the study with the mean (SD) age of 26.8 (15.5) years. They encompassed low bleeding risk circumstances including avoidance of contact sports and high velocity activities. Four adults initially received episodic treatment and subsequent low dose prophylaxis at 15-20 units/kg twice weekly but breakthrough bleeding episodes frequently occurred. The only boy also received low dose prophylaxis at 14 units/kg once weekly at the age of 5.9 years and increased to twice weekly one month later due to frequent spontaneous bleeding at the right knee. However, the difficulty in venous access created constraint in achieving adequate prophylaxis. Therefore, all patients were switched to receive the whole vial of emicizumab at the monthly low dose ranging from 1.14 to 1.25 mg/kg without 4-loading doses for 2 years and sequential use of median (IQR) monthly low dose emicizumab of 1.50 (1.31, 1.65) mg/kg in the first week and factor VIII concentrate 15 units/kg twice weekly in the 4 th week in the third year. The duration of follow-up in the third year was 6 months. The results revealed the median (interquartile range, IQR) trough level of plasma emicizumab concentration at the 4 th weeks before factor VIII administration determined by a modified one stage factor VIII assay using emicizumab calibrator was maintained at 8.5 (6.2,10.8) µg/mL. The median (IQR) APTT of all patients at 6-month prophylaxis of 25.7 sec (25.3, 26.0) was shortened compared with a baseline of 66.9 sec (54.3, 105.1) demonstrating the presence of emicizumab and the likely absence of anti-emicizumab antibodies. Also, no inhibitor to factor VIII clotting activity was detected among all patients before and after prophylaxis. Their median (IQR) annual bleeding rate significantly decreased from baseline of 30.0 (13, 36.5) to 5.0 (3, 12.5) in the first year, 1.0 (0.5, 8.5) in the second year and 1 (0, 3) in the third year of prophylaxis with p-values of 0.043. Impressively, zero annual bleeding rate in the third year of the current study was found among 2 patients while 2 patients exhibited one episode of trauma-related bleeding at the ankle and one patient had frequent epistaxis from high PM 2.5 in his hometown. Ultimately, all patients achieved annual spontaneous joint bleeding rate ≤1 episode during a 6-month period of sequential use of emicizumab and factor concentrate prophylaxis. In addition, quality of life, HJHS, HEAD-US and ultrasonography study were improved in all studied patients. Factor VIII concentrate was helpful in preventing bleeding especially at the 4 th week after administering emicizumab and providing other biological activities beyond hemostasis related to bone remodeling, dysregulated macrophage polarization and inflammatory processes among studied patients. Conclusion: The sequential use of monthly low dose emicizumab and factor VIII concentrate prophylaxis showed effectiveness with annual spontaneous joint bleeding rate ≤1 episode among all studied patients. The musculoskeletal system and quality of life were also improved.

Emicizumab Efficacy in Severe Hemophilia (A): Experience in Ecuador

Introduction: In Ecuador, there are 1708 cases of hemophilia in a population of 17,643,060 habitants; according to the World Federation of Hemophilia (WFH) Annual Global Survey Report 2020 released in October 2021. Eleven patients use emicizumab in Ecuador (ten patients under ministerial authorization, and one patient through private insurance); being the first administered in June 2021. Objectives: To describe the demographic characteristics of patients receiving emicizumab in Ecuador. To determine efficacy and response with emicizumab: based on annual bleeding rate (ABR), performance status assessment, activity, and participation. Methods: Population: Pediatric Severe Hemophilia A (PwHA) patients (&amp;lt;12 years) and adults/adolescents (&amp;gt;12 years), both from the public and private health sector. Study design: Retrospective, multicentric study, with a case-report research design. The sources of information were the medical records of the patients. Efficacy variables: ABR was calculated by: (number of bleeds/number of days times 365.25). Body structure and function was assessed with the Hemophilia Joint Health Score 2.1 (HJHS). Activity and participation were assessed with the Functional Independence Score in Hemophilia (FISH). Statistic analysis: Shapiro-Wilk test to know the distribution of the sample, t-Test paired tests (parametric), Wilcoxon statistic (non-parametric); Descriptive statistics: relative frequencies, measures of central tendency and dispersion, column graphs. Analysis and results: Ten patients with an average (Q1,Q3) age of 11.5 years (7.15) were registered. The youngest patient was one year old and the oldest, fifty years old. 90% (n:9) had hemophilia A with high-response inhibitors. Prior to starting emicizumab: 20% (n:2) presented Central Nervous System bleeding, 30% (n:3) had muscle bleeding, and 10% (n:1) developed catheter-associated infection. The mean ABR was 10 pre-emicizumab events, and 0.3 post-emicizumab events (p=0.002), with follow-ups at 22 months (n: 2), 17 months (n:2), 3 months (n:2 ), 4 months (n: 3), 5 months (n: 1). The mean HJHS (±SD, n) was 20.9 (± 20,096, 10) pre-emicizumab, and 9.7 (± 16.52, 10) (p=0.003) The mean by FISH (±SD, n) was 16.2 (± 8.59, 10) pre-emicizumab, and from 22.6 (± 11.62, 10) with the use of emicizumab. The use of the t-Test for paired samples determined that there are statistically significant differences between the pre-emicizumab and post-emicizumab groups for the variables ABR, HJHS and FISH (95% confidence level). Conclusion: The use of Emicizumab allowed better control of joint bleeding; and it contributed favorably in the evolutionary course of both the functional state and the activity. It is essential to corroborate these results with a longer follow-up and a larger sample size. Bibliography: 1. Alvarez Roman M: Spanish guidelines for the management of hemophilia. 2022, 1-190. 2. Callaghan M, Negrier C, Paz-Priel I, Chang T, Chebon S y col: Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1-4 studies. Blood. 2021;137(16):2231-2242 3. Carcao M, Escurriola C, Santagostina E, Oldenburg J, Liesner R y col: The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab. Haemophilia. 2019;25:676-684. 4. Ellsworth P, Ma A: Factor-mimetic and rebalancing therapies in hemophilia A and B: the end of factor concentrates?. Hematology Am Soc Hematol Educ Program. 2021, Dec 10;2021(1):219-225. 5. Young G: Management of children with hemophilia A: How emicizumab has changed the landscape. Journal of Thrombosis and Haemostasis. 2021 Jul;19(7):1629-1637

Chronic Disease Outcomes As Predictors of Quality of Life in Patients with Hemophilia Α: Data from the Real-World AHEAD International Study

Background: Hemophilia A (HA), a genetic disorder caused by deficient or defective factor VIII (FVIII) clotting protein, has a significant impact on patients' quality of life (QoL).The international Antihemophilic factor Hemophilia A outcome Database (AHEAD) study (NCT02078427) is an ongoing prospective, non-interventional, multicenter study evaluating the long-term safety and effectiveness of FVIII replacement in patients with HA receiving either octocog alfa or rurioctocog alfa pegol (ADVATE®; ADYNOVATE® [US] / ADYNOVI™ [Europe]; Baxalta US Inc., a Takeda company Lexington, MA, USA) in routine clinical practice. Aim: This analysis aimed to evaluate the association between chronic disease outcomes and QoL in patients with moderate or severe HA without an active inhibitor and treated with octocog alfa. Methods:Male patients aged ≥18 years with moderate (FVIII 1-≤5%) or severe (FVIII &amp;lt;1%) HA without an active inhibitor and receiving octocog alfa were included in the analysis. Data were included across study years 1 to 5 for patients with all model variables reported in at least one study year. Cut off was set at year 5 as smaller sample sizes in later years did not allow for appropriate statistical modelling due to natural attrition and loss to follow up. The association between chronic disease outcomes and QoL was estimated using a Mixed Effects Model with repeated measures. The model assessed the impact of chronic pain (classified as no pain [used as the reference], mild pain, moderate pain, or severe pain) and number of problem joints (PJs; identified through the reporting of relevant components of the hemophilia joint health score, Gilbert Score and/or Petterson score) on EQ5D 3L index score (calculated using UK value set), controlling for clinical and demographic characteristics (annualized bleeding rate [ABR], HA severity, body mass index [BMI], and age at visit), in addition to individual patient effect, via the random effects component. The random effects component allows the model to control and account for individual patient effects that may not be measured by available independent variables but that may influence the output of the analysis. Results:The final analysis included 175 adult male patients with an average (range) of 2.1 (1-5) study years. The majority (70%) of patients had severe HA. At study year 1, the mean ± SD age was 33.6 ± 12.7 years and the mean ± SD number of PJs was 3.8 ± 2.0, while 47% of patients reported some level of chronic pain, with 20% of patients reporting moderate or severe pain levels. Mean ± SD EQ5D 3L index score was 0.77 ± 0.21 at study year 1. Overall, after controlling for demographic and clinical characteristics, and any individual patient effect, chronic outcomes (chronic pain and number of PJs) were found to have a statistically significant negative association with QoL (Table). The negative association of chronic pain with EQ5D 3L index score was greater with increasing pain level (mild, -0.082; moderate, -0.135; severe -0.169; P≤0.001). Number of PJs was also negatively associated with EQ5D 3L index score (P=0.005) with a decrease of -0.018 for each additional problem joint. Age at visit also showed a negative association with EQ5D 3L index score (-0.004; P=0.002). ABR, HA severity, and BMI did not have a statistically significant association with EQ5D 3L index score. Conclusions: In this Mixed Effects Model, chronic pain level and number of PJs both had a statistically significant negative association with QoL, highlighting the importance of managing these chronic outcomes with effective treatment.

Three-Year Interim Analysis Results of the AOZORA Study to Evaluate the Long-Term Safety and Joint Health in Children with Hemophilia A without Factor VIII Inhibitors Receiving Emicizumab

Background: Recurrent joint bleeding from a young age in people with hemophilia A (PwHA) may lead to hemophilic arthropathy, resulting in limited movement and chronic pain. Emicizumab is a bispecific monoclonal antibody that bridges activated factor (F) IX and FX to substitute for activated FVIII and provides stable plasma concentrations and maintenance of trough levels within the therapeutic range. Limitations in long-term joint health preservation have been reported with FVIII prophylaxis (Warren et al. Blood Adv 2020); it is expected that emicizumab may overcome these limitations, as joint health improvements have been demonstrated in PwHA aged 12-39 years (Kiialainen et al. Haemophilia 2022). Here, we report the 3-year interim analysis of the ongoing, open-label, Phase IV AOZORA study (JapicCTI-194701), analyzing long-term safety and joint health in pediatric PwHA without FVIII inhibitors receiving emicizumab (Shima et al. BMJ Open 2022). Methods: Eligible participants were aged &amp;lt;12 years with severe hemophilia A (HA) without FVIII inhibitors. Participants entered AOZORA as emicizumab-naïve or following the Phase III HOHOEMI study (Shima et al. Haemophilia 2019). Primary endpoints include adverse events (AEs), and joint health and function assessed by magnetic resonance imaging (MRI) and the Hemophilia Joint Health Score (HJHS) version 2.1. MRI evaluation uses the International Prophylaxis Study Group (IPSG) MRI scale; a positive IPSG score indicates pathological changes in the knee and/or ankle joints. Exploratory endpoints include annualized bleed rate (ABR) for treated bleeds and treated joint bleeds. All participants will receive emicizumab for 6 years from their first dose until study end. Results: Data cut-off was the last day of Week 145 for individual participants. Ten participants entered from HOHOEMI and 20 participants were newly enrolled. The median (range) age was 4.2 (0.7-11.1) years, all participants were male, and 27 (93.1%) participants had been treated with prior FVIII prophylaxis ( Table 1). One participant had 1 target joint (knee) at Week 1. In AOZORA, 5 (16.7%) participants experienced 7 emicizumab-related AEs: 6 injection site reactions in 5 participants and 1 case of anemia in 1 participant. Seven serious AEs, reported as unrelated to emicizumab, occurred in 5 (16.7%) participants. No thrombotic events or thrombotic microangiopathies occurred. Twenty-nine participants at Week 1 and 26 participants at Week 145 were assessed using the IPSG MRI scale. At Week 145, MRI scores remained at 0 for 11 (42.3%) of the 26 participants. Of 116 joints assessed at Week 1, 28 (24.1%) had soft tissue changes (effusion/hemarthrosis, synovial hypertrophy and/or hemosiderin deposition; Table 2). At Week 145, 104 joints were assessed and 33 (31.7%) of those had soft tissue changes. Of 10 (8.6%) joints with synovial hypertrophy and hemosiderin at Week 1, all had improved at Week 145 and synovial hypertrophy and hemosiderin were no longer present in 9 joints. One new joint developed synovial hypertrophy and hemosiderin at Week 145. The rest of the soft tissue changes were effusion/hemarthrosis, present in 21 (18.1%) joints at Week 1 and 31 (29.8%) at Week 145. Thirty participants at Week 1 and 27 participants at Week 145 were assessed using the HJHS v2.1. Eighteen (66.7%) participants' HJHS scores remained at 0 from Week 1 to Week 145 and 1 (3.7%) participant's remained at 4; 6 (22.2%) participants' scores improved; 2 (7.4%) participants' scores worsened. Mean (standard deviation) HJHS total score improved from 0.90 (1.79) at Week 1 to 0.44 (1.05) at Week 145. The mean (95% confidence interval [CI]) ABR for treated bleeds was 3.7 (0.94-9.80) prior to emicizumab and 0.7 (0.01-5.10) while receiving emicizumab. The mean (95% CI) ABR for treated joint bleeds was 0.4 (0.00-4.55) prior to emicizumab and 0.2 (0.00-4.04) while receiving emicizumab. Conclusions: This 3-year interim analysis of the AOZORA study confirmed the safety profile of emicizumab. The proportion of joints with effusion/hemarthrosis increased by Week 145. However, all joints with synovial hypertrophy and hemosiderin, which are strongly associated with the progression of arthropathy (Gualtierotti et al. J Thromb Haemost 2021), improved by Week 145. These results suggest that emicizumab is effective in maintaining and improving joint health in pediatric PwHA.

Changes in Health-Related Quality of Life, Pain and Functional Parameters in People with Hemophilia and People with Osteoarthritis - a Comparative Follow-up of Physiotherapeutic Training (Physio-FUN Study)

Background: Spontaneous joint bleeding is common in people with hemophilia (PWH). These bleeds lead to reduced physical activity and thus to a weakening of the musculature. Common sequelae of this are synovitis and cartilage damage. In the long term, secondary osteoarthritis, so-called hemophilic arthropathy, occurs with changes and progressive destruction of joint structures (Lafeber et al., 2008). Hemophilic arthropathy is age-independent and can lead to severe movement restrictions and significant limitations in health-related quality of life (HRQoL) of affected PWH (Varaklioti et al., 2018). To prevent advanced stages of arthropathy not only regular assessment of musculoskeletal status and early detection of symptoms, but also daily rehabilitation exercises at home, and implementation of appropriate physiotherapy and medical training are important (Bossard et al., 2008). Home exercises and manual therapy can be used without causing bleeding or pain to improve pain, HRQoL and functionality (Tat et al., 2021). The primary aim of the Physio-FUN study was to assess the subjective (Hemophilia Exercise Project Test-Questionnaire [HEP-Test-Q]) and objective physical functioning (Hemophilia Joint Health Score [HJHS]) during the course of 1-year applied physiotherapy comparing PWH with arthropathy and patients with osteoarthritis (PWO). Methods: In this prospevtive, controlled monocentric cohort study it was planned to enroll 20 adult PWH A or B compared to 20 gender-matched adult PWO without a bleeding disorder. Patients with a blood pressure ≥ 180/110 mmHg were excluded. A positive ethical approval for the study was obtained by the Ethics Committee North Rhine, Germany. After informed consent had been obtained, the study participants underwent examinations based on clinician-reported outcomes (ClinRO) and performance outcomes (PerfO) and completed different patient-reported outcomes (PROs). ClinROs included ultrasound, functional movement screen (FMS) and the collection of anthropometric and clinical data; PerfOs included cardiopulmonary performance, 6-minute walk test (6MWT), blood pressure measurement before and after 6MWT, joint mobility (neutral-zero method) and Functional Movement Screen (FMS) to evaluate movement pattern quality; PROs included the assessment of sociodemographic data, HRQoL (SF-12), Physical Activity Questions (EPIC - Simple Index), pain sensation scale (SES) and Borg Rating of Perceived Exertion (RPE) measuring physical activity intensity level. All patients took part in regular physiotherapy (once a week) at the ARZD as prescribed by a physician. During the study, PWH continued to receive their usual hemophilia treatment regimen without study-related changes. Over a period of 12 months, ClinROs, PerfOs and PROs were collected repeatedly on a quarterly basis. Each patient was supposed to participate in 5 measure points (baseline, every 12 weeks over a one-year period). Ultrasound examinations were performed at baseline and at the conclusion at MZP5 in all patients. Results: At baseline 17 PWH (mean age 43.29±13.1 years) and 12 PWO (mean age 61.42±8.5 years) were enrolled; most PWH had HA (88.2%) were severely affected (58.8%) and 6/17 had a knee endoprosthesis. 88.2% of PWH had a disabled card (most with a disability degree of ≥ 80) compared to 45.5% of PWO (most with a disability degree of 50). PWH had a significant worse orthopaedic joint status ( p&amp;lt;.002) and subjective physical functioning ( p&amp;lt;.001) compared to PWO; PWH had a mean HJHS of 26.76±18.0 vs. 11.0±5.7 and a mean HEP-Test-Q of 48.12±16.4 vs. 67.08±9.1. PWO reported highest impairments in the domain ‘mobility’, while PWH suffered mainly under reduced ‘endurance’. With respect to their age, height and weight most of the PWH were below the predicted lower limit of the 6MWD compared to the PWO who all were above the lower limit of the 6MWD. No difference was found between the groups regarding FMS (11.34±3.8) and RPE before (11.5±3.3) after 6MWT (11.5±3.3). Conclusions: Our study took place during the Corona pandemic and was quite time consuming for the participants, resulting in a failure to reach the desired number of cases and lead to a high drop-out rate over the duration of the project. Although PWH were significantly younger than PWO, they had a significantly worse subjective (HEP-Test-Q) and objective physical functioning (HJHS).

Effectiveness of Kinesiologic Taping on Function and Pain in Patients With Hemophilia A

ABSTRACT Background: Hemophilic arthropathy frequently results in musculoskeletal adjustments that impair functional capacity. Aim: We investigated the effects of kinesiologic taping on patients with hemophilic arthropathy in this study. Materials and Methods: Twenty-six patients were enrolled. Thirteen patients formed the Kinesiologic taping group (KT) and received the interventional protocol consisting of three kinesiologic taping sessions during three weeks; and 13 patients formed the control group (CG) and made three weeks of home exercises. All patients were evaluated using the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and Visual Analog Scale (VAS) at baseline, one week, and three weeks. Results: The mean scores for the VAS, HJSS, and FISH differed significantly before and after 3 weeks in both groups (P &lt; 0.001). However, the differences in medians after the treatment were significantly greater in the KT group than in the CG group (P &lt; 0.001). Conclusions: Kinesiologic taping was associated with physical improvement in hemophilia patients; however, also kinesiologic taping led to significant improvement in VAS scores.

Association between the levels of serum vitamin D and trace elements and joint health in children with hemophilia

Hemophilia is defined as X-linked recessive bleeding disorder. Recurrent bleeding episodes lead to hemarthrosis.Objectives: to investigate the levels of serum 25(OH) D and trace elements in children with hemophilia A and B and to identify the possible association of these factors with Hemophilia Joint Health Score (HJHS). This case-control study was conducted among children with hemophilia A and B. A total of 48 cases were recruited from the hematology units at the Menoufia University Hospital (n = 36) and Sohag University Hospital (n = 12) from December 2020 to February 2022. Forty healthy controls were matched to cases on age, sex and socioeconomic status. Serum zinc and magnesium levels in the hemophilia patients were significantly lower than in the controls, while serum alkaline phosphatase levels in the cases were significantly higher than in the controls. Informed consent was obtained from all the children's parents and ethical approval was acquired from the ethical committee (ID: 5/2020PEDI38), Faculty of Medicine, Menoufia University. The levels of phosphorus and calcium were the same in two groups. Serum 25(OH) D levels were deficient in 85.4% of the cases and insufficient in 14.6%. None of the hemophilia patients had sufficient levels of serum 25(OH) D. There was no significant correlation between HJHS and the levels of serum trace elements but there was a significant positive correlation between HJHS and annualized bleeding rate and a significant negative correlation between HJHS and serum vitamin D. There was no significant difference regarding the demographic data except for weight and body mass index. The patients had significantly higher weight and body mass index compared to the control group. The levels of serum vitamin D and trace elements were decreased in hemophilia patients, and these low values were associated with the worst joint health.

Evaluation of Functional and Joint Health and Associated Factors in Adults With Hemophilia From a Developing Country With Government-Backed Efforts to Improve Hemophilia Care.

Introduction Hemophilic arthropathy affects people with hemophilia (PwH) and causes joint dysfunction and disability. Brazil has a unique situation and implemented policies to improve health care for PwH. The aim of this study was to evaluate the Functional Independence Score in Hemophilia (FISH), Hemophilia Joint Health Score (HJHS), and associated factors among adult PwH attending a Hemophilia Comprehensive Care Center in Brazil. Methods A post hoc analysis was conducted, including 31 patients who had submitted to a physical evaluation during a previously published cross-sectional study performed from June 2015 to May 2016 at the Brasília Blood Center Foundation, Brazil. Results The mean age was 30.8±9.4 years, and 80.6% had severe hemophilia. FISH was 27.0±3.8, and HJHS 18.0±10.8. The ankle was the most often affected joint (25/31, 80.6%). There were significant correlations between FISH and HJHS scores and the Hemophilia Quality of Life Questionnaire for Adults. Patients with severe hemophilia (P = 0.029) and PwH aged ≥ 30 years (P = 0.049) had lower FISH scores. Monthly household income > 2 Brazilian minimum wages was independently associated with improved HJHS (P = 0.033). The factors simultaneously associated with better HJHS and FISH were age < 30 years (P = 0.021) and monthly household income < 2 minimum wages (P = 0.013). Conclusion FISH and HJHS showed favorable scores despite being performed in a country with unfavorable socioeconomic conditions. In addition to hemophilia severity and age, monthly household income was independently associated with functional and articular state of PwH. The results highlight the importance of the free provision of coagulation factors in Brazil.

Prophylaxis with a recombinant factor VIII Fc in hemophilia A: long-term follow-up on joint health, efficacy, and safety from phase 3 studies in children and adults

BackgroundRecurrent joint bleeds are a major cause of morbidity in severe hemophilia. Prophylaxis with efmoroctocog alfa (a recombinant factor VIII Fc fusion protein, [rFVIIIFc]) has demonstrated benefits beyond bleed control, including joint health maintenance. ObjectivesTo assess long-term efficacy and safety of rFVIIIFc prophylaxis in severe hemophilia A in phase 3 pivotal (A-LONG/Kids A-LONG) and extension (ASPIRE) studies. MethodsLongitudinal analysis included pooled data from A-LONG/Kids A-LONG and ASPIRE. Subgroup analyses investigated outcomes in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score and target joints in subjects with 4 to 5 years follow-up on individualized prophylaxis (IP), and those with the highest annualized bleeding rate (ABR) quartile during Year 1 of IP. ResultsOverall, rFVIIIFc consumption remained stable and low ABRs were maintained, with a median treatment duration of 4.2/3.4 years in subjects from A-LONG/Kids A-LONG, respectively. Median overall ABR also remained low (1.0-2.0) in subjects on IP for 4 to 5 years. Sustained improvements in modified Hemophilia Joint Health Score or Hemophilia Joint Health Score were demonstrated over a median follow-up of 3.7 years. In subjects from A-LONG/Kids A-LONG, 99.6% (n = 234)/100% (n = 9) of evaluable baseline target joints were resolved, with no recurrence in 95%/100% of target joints. In IP subjects within the highest ABR quartile in Year 1, continued improvements were observed over a median follow-up of 4.3 years in ABR and joint health, without increased factor consumption. No inhibitors or treatment-related serious adverse events were reported. ConclusionPreviously treated subjects of all ages receiving long-term prophylaxis with rFVIIIFc had sustained clinical benefits, including improved joint health and low ABR.

Long-term outcomes of prophylaxis with a recombinant factor VIII Fc or recombinant factor IX Fc in patients with hemophilia previously treated on demand

BackgroundProphylactic factor replacement therapy is recommended over on-demand treatment for preserving long-term joint health in hemophilia. Extended half-life products, including efmoroctocog alfa/eftrenonacog alfa (recombinant factor VIII [FVIII]/FIX Fc fusion proteins; herein rFVIIIFc/rFIXFc), have the potential to reduce treatment burden with less frequent administration and improve bleed prevention. ObjectivesWe report post hoc data from patients with hemophilia A or B (HA/HB) who switched from prestudy on-demand FVIII/FIX to rFVIIIFc/rFIXFc prophylaxis at the start of A-LONG/B-LONG or start of/during ASPIRE/B-YOND phase 3 studies. MethodsPatients with ≥6 months rFVIIIFc/rFIXFc prophylaxis were enrolled. Treatment exposure, dosing, annualized bleeding rates, joint health, and health-related quality of life (HRQoL) outcomes were assessed. Results were also stratified by age. ResultsSixty-seven patients with HA and 50 with HB were analyzed; ≥60% were from regions outside Europe/North America, predominately those aged 12 to ‍25 years. No subjects returned to on-demand treatment postswitch.After switch to rFVIIIFc/rFIXFc prophylaxis, median annualized bleeding rates were reduced and sustained at low levels with stable factor usage across age groups (median treatment duration: 4.8/3.6 years). HRQoL outcomes improved for all ages; most pronounced changes were in the sports and leisure and physical health domains. After switch to rFVIIIFc prophylaxis, total modified Hemophilia Joint Health Score and joints with pain decreased in 64.6% and 29.2% of patients with HA. Insufficient data from patients with HB limited joint health evaluation of rFIXFc. ConclusionsFindings add to existing evidence and demonstrate the clinical and HRQoL benefits of switching patients from on-demand treatment to rFVIIIFc/rFIXFc prophylaxis.

Comparison of joint status using ultrasound assessments and Haemophilia Joint Health Score 2.1 in children with haemophilia.

Ultrasound (US) has gained popularity in the evaluation of haemophilic joint diseases because it enables the imaging of soft-tissue lesions in the joints and bone-cartilage lesions. We aimed to determine the correlation between US evaluations and clinical assessments performed using HJHS 2.1 and to evaluate their respective characteristics in assessing early haemophilic arthropathy. A total of 178 joints (32 knees, 85 elbows, and 61 ankles) in 45 haemophilia A patients (median age, 10 years; range, 6-15) were assessed using US and HJHS 2.1. Ultrasonographic scoring was performed in consensus assessments by one imager by using the US scores. The total HJHS 2.1 and US scores showed a strong correlation (rS=0.651, P=0.000, CI: 0.553-0.763), with an excellent correlation for the elbows (rS=0.867, P=0.000, CI: 0.709-0.941) and a substantial correlation for the knees (rS=0.681, P=0.000, CI: 0.527-0.797). The correlation for the ankles was relatively moderate (rS=0.518, P=0.000, CI: 0.308-0.705). Nine subjects (15.5%) without abnormalities, as indicated by HJHS 2.1, showed haemophilic arthropathy in US scoring. All nine joints showed moderate (1/9) to severe (8/9) synovial thickening in the ankle (5/9) and elbow joints (4/9). In contrast, 50 joints (50.5%) showed normal US scores and abnormal changes as indicated by HJHS 2.1. S scores correlated well with HJHS 2.1 for overall and individual joints. US could identify some early pathological changes in joints showing normal clinical findings, but still cannot replace the HJHS; however, it can serve as an imaging examination complementing HJHS 2.

Ultrasound Evaluation of Tendinopathy in Hemophiliac Patients for the Purpose of Rehabilitation Indications.

Hemophilia is a inherited bleeding disorder that is characterized by intra-articular bleeding (hemarthrosis). The aim of the study was to evaluate the state of the satellite tendons of the target joints in the patient with hemophilic arthropathy and propose rehabilitation treatment with eccentric exercises. The tendons of the joints mainly affected by hemophilic arthropathy were evaluated by ultrasound. The ultrasound evaluation is associated with the use of evaluation clinical scales, such as the Hemophilia Joint Health Score (HJHS), the Functional Independence Score in Hemophilia (FISH), the Hemophilia Activity List (HAL), the DASH, the VISA-A, the VISA-P, and the VAS scale. In 20 patients with hemophilic arthropathy, the thickness of the tendons that were examined was normal. In six subjects with severe joint damage, echostructural alterations were present, and signs of hyperemia and neo-vascularization were detected on color Doppler, as well as the presence of intratendinous calcifications. The tendons of the target joints in patients with hemophilic arthropathy are compromised by the indirect biomechanical damage caused by the joint disease, and rehabilitation treatment with eccentric exercises can be considered safe and effective in improving the tenso-elastic properties of the tendons.

Haemophilia joint health score (HJHS) usage, patterns and outcome data in patients with haemophilia A and haemophilia B in Australia: A descriptive study using the Australian Bleeding Disorders Registry (ABDR).

Assessment of joint health is an essential component of haemophilia management. A variety of clinical tools have been developed to standardise this assessment process. One such tool, the Haemophilia Joint Health Score (HJHS), is embedded for use within the Australian Bleeding Disorders Registry (ABDR). This provides a unique opportunity to analyse patterns of tool usage as well as associations between scores, demographics and clinical outcome factors. To characterise clinician practices regarding use of HJHS in routine clinical assessment of persons with haemophilia (PWH), to examine relationships between HJHS, and age, inhibitor status and body mass index (BMI), and to identify potential barriers to HJHS tool usage. A national, retrospective study was conducted using data extracted from the ABDR between 2014 and 2020, complemented by a qualitative questionnaire exploring haemophilia treatment centre (HTC) structure, resourcing and clinician perspectives about HJHS. 28.1% (622/2220) of PWH had at least one HJHS recorded in the ABDR during the defined study period (546 haemophilia A, 76 haemophilia B). HJHS were recorded more in children than adults and performed more in severe than non-severe haemophilia. Multivariate analysis demonstrated significant association of age, severity and inhibitor status with HJHS. No association was identified between BMI and HJHS. Qualitative surveys revealed significant variation in physiotherapy funding, availability and methods of tool use between HTCs. This study provides valuable insights into joint health assessment in Australia. It improved our understanding of factors influencing long-term joint outcomes. Practical limitations of HJHS tool were also discussed.