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Background Methods Results Conclusions Highlights In Thailand, an upper‐middle‐income country, managing haemophilia A (HA) with inhibitors poses significant challenges, often necessitating bypassing agents (BPAs) for bleeding control. This study evaluates the cost‐effectiveness and budget impact of emicizumab, a novel prophylactic agent, as an alternative to both episodic and prophylactic BPA treatments from a societal perspective.A Markov model was employed to estimate the lifetime societal costs and outcomes of emicizumab prophylaxis for HA patients with inhibitors. Treatment efficacy, cost, and epidemiological data were obtained through a comprehensive literature review and incorporated into the model. A 5‐year budget impact analysis complemented the cost‐utility analysis, with a 3% annual discount rate applied to future costs and outcomes.In the base‐case scenario, emicizumab prophylaxis in HA patients aged 2 years and above demonstrated superior cost‐effectiveness, yielding 18.1 quality‐adjusted life years (QALYs) per patient over a lifetime and resulting in cost savings of 138 million Thai Baht (THB) compared to BPA prophylaxis. Compared to episodic BPA treatment, emicizumab yielded 30.5 QALYs and saved 25 million THB per patient. The 5‐year budget impact was projected at 1775 million THB.Emicizumab offers a cost‐saving approach for HA treatment with inhibitors in Thailand, promising significant health benefits and budgetary savings. This supports its potential inclusion in Thailand's National List of Essential Medicines to enhance haemophilia care access. Managing haemophilia A (HA) with inhibitors in Thailand, an upper‐middle‐income country, faces challenges due to limited access to effective treatments or newer drugs for bleeding management. Emicizumab prophylaxis found to as a cost‐effective and viable alternative to traditional treatments, effectively preventing bleeding in Thai HA patients over 2 years old with inhibitors. Demonstrating improved clinical outcomes and reduced costs, emicizumab prophylaxis outperforms episodic BPA treatments, positioning it as a superior treatment option for HA patients with inhibitors in Thailand. [ABSTRACT FROM AUTHOR]

Introduction: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. Aim: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real‐world setting. Methods: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. Results: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0–30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0–4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0–12.0) and 4.2 (3.0–6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. Conclusion: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full‐dose emicizumab is ill affordable. [ABSTRACT FROM AUTHOR]

Introduction: Non‐factor replacement therapies are emerging as prophylactic treatment options in haemophilia A or B (HA/HB) with and without inhibitors. Concizumab is an anti‐tissue factor pathway inhibitor (TFPI) monoclonal antibody preventing factor (F)Xa inhibition and enhancing thrombin generation. Based on experience with other non‐factor therapies and extended half‐life products, there is a focus on potential interference with common clinical coagulation assays used to monitor patients treated with concizumab. Aim: To evaluate the impact of concizumab on standard clinical coagulation assays. Methods: Plasma samples (normal, HA/HB with/without inhibitors) in the presence/absence of added concizumab (250–16,000 ng/mL) were analysed in clinical assays including activated partial thromboplastin time (aPTT), prothrombin time (PT), FVIII and FIX one‐stage clot and chromogenic substrate assay, assays for detecting FVIII or FIX inhibitors and other assays for coagulation factors. Results: Concizumab did not impact PT assays, but resulted in a small shortening of aPTT (up to 5 s in haemophilia plasma and 0.4 s in normal plasma). Concizumab had no, or only a minor impact on FVIII and FIX activity assays or Bethesda inhibitor assays. FXI and FXII activity in normal plasma, as measured by single factor aPTT‐based assay, was significantly increased in the presence of concizumab (+11% each). This was also the case for FVII and FX measured by PT‐based assays using plasma with 25% of FVII or FX (+64% and +22%, respectively). Conclusion: The presence of concizumab did not, or only slightly, influence the outcome of standard clinical coagulation assays relevant for HA and HB. [ABSTRACT FROM AUTHOR]

Introduction: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options. Aim: Describe current treatments and outcomes for GI BEs in people with VWD. Methods: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI‐specific morbidities/lesions, treatment and outcomes were analysed descriptively. Results: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5‐year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non‐haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non‐VWF treatments tended to resolve later. In patients with GI‐specific morbidities/lesions, 84% resolved with first‐line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on‐demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution. Conclusions: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Tailored prophylaxis is the current treatment regimen for patients with severe haemophilia A. Recently, published guidelines describe two possible approaches, based on clinical characteristics or estimation of pharmacokinetic parameters. However, both have strengths and weaknesses, and their characteristics need to be integrated to optimize treatment appropriately. In this paper, we present a model that considers together the characteristics of prophylaxis and the relevance of each. Methods: The age at initiation of prophylaxis, number of bleeding events, treatment regimen, therapeutic adherence, FVIII trough levels, and joint status were analyzed in 59 patients followed at La Paz University Hospital between January 2000 and December 2019. Results: The mean duration of primary prophylaxis of 113.37 ± 57.79 months. Eighty‐three percent (n = 49) had no joint status involvement at the end of follow‐up (HJHS and HEAD‐US = 0). The median ABR was 0.7 (IQR 0.2 –1.0) and 54.2% presented trough levels of FVIII during follow‐up >1 IU/dL. 72,9% engaged in some type of physical activity and overall adherence was over 85% in all patients evaluated. The regression analysis performed, considering all these factors, showed that the initiation of prophylaxis before 21 months of age was the most relevant protective factor against the appearance of joint involvement (OR 88.33 p.031 CI 95% 1.49‐5224.40) Conclusion: Early initiation of prophylaxis was the most relevant factor in the protection of joint status. More comprehensive analysis models adapted to the characteristics of each population, are needed to adequately individualize treatment. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia A negatively affects a patient's quality of life. There is a limited amount of health utility data (a measure of health‐related quality of life) available for patients with haemophilia A. This information is crucial for cost‐effectiveness analysis for haemophilia A treatment. Objectives: The goal of this project is to elicit the health utilities and factors impacting utility values for haemophilia A patients in Canada. Methods: This is a population‐based, cross‐sectional, retrospective study of health utilities in patients with haemophilia A using Patient Report Outcomes Burdens and Experiences (PROBE) components from the Canadian Bleeding Disorders Registry (CBDR). A review of the mean utilities for three severity states, defined by clotting factor VIII level, was completed. A multiple linear regression analysis was completed to examine the determinants of health utilities including age, treatment type, chronic pain status, number of limited joints, and bleed rate. Results: The average utility values (and standard deviations) for patients with haemophilia A in Canada are.79(.17),.76(.20), and.77(.19) for patients with severe, moderate, and mild haemophilia. The regression showed chronic pain status and the number of additional comorbidities as major significant factors (p‐value <.001) in haemophilia A utility. Haemophilia severity was shown to be a major factor with smaller p‐value (p‐value <.05). Conclusions: Haemophilia A patients have lower utility than the general population. Chronic pain was shown to be a significant, major factor in health‐related quality of life. Our study is essential for valuing health outcomes in haemophilia A‐related cost‐effectiveness analysis. [ABSTRACT FROM AUTHOR]

Introduction: Over the last decades progress in haemophilia treatment has been remarkable and prophylaxis with clotting factor concentrates in haemophilia A and B has been established as the standard of care in individuals with haemophilia and a severe bleeding phenotype. Besides clotting factor products with prolonged half‐life non‐factor therapies were developed which enable prophylaxis via subcutaneous administration. Factor VIIIa mimetics like emicizumab facilitate the coagulation pathway and are used in routine clinical practice for indivdiduals with haemophilia A. Rebalancing therapeutic agents like fitusiran, concizumab, marstacimab and serpin PC block the anticoagulant pathway and clinical trials using these products in individuals with haemophilia A and B are ongoing. Aim and Methods: A narrative review to asess the benefits and risks of non‐factor therapies taking in to account re‐defined haemophilia treatment goals. Results: Prophylaxis for prevention of bleeds using non‐factor products by subcutaneous administration is effective and results in reductions of bleeding episodes in individuals with haemophilia A or B with and without inhibitors. The treatment with emicizumab showed tolerable safety both in clinical trials and long‐term real‐world observations with few thrombotic events. In some clinical trials with rebalancing therapies (fitusiran and concizumab) thrombotic events occurred. Monitoring of the haemostatic function of novel therapies especially with concomitant haemostatic treatment is not yet established. Conclusion: With the advent of novel therapeutic agents including factor concentrates with ultra‐long half‐life and improved FVIIIa mimetics aimed at raising the bar of protection into the non‐hemophilic range redefinition of haemophilia treatment goals is eagerly needed. [ABSTRACT FROM AUTHOR]

Introduction: Prophylaxis has become standard of care for all persons with haemophilia (PWH) with a severe phenotype. However, 'standard prophylaxis' with either factor or non‐factor therapies (currently only emicizumab available) is prohibitively expensive for much of the world. We sought to address the question of 'How much prophylaxis is enough?' and 'Can it be individualized?' and specifically 'Can emicizumab be individualized?'. Methods: We reviewed the literature on prophylaxis in haemophilia since its inception in the 1950s to the present, the development of more and less intense factor prophylaxis regimens and their outcomes and additionally the published outcomes of prophylaxis with low dose emicizumab. Results: What these experiences collectively show is that low dose emicizumab does result in significant benefits to patients whilst being much less expensive than a "one size fits all" emicizumab prophylaxis approach. We also took note that some non‐factor therapies still in development are individualized given that high doses of these can potentially put patients at risk. Conclusions: Prophylaxis is now clearly accepted as standard of care for PWH with a severe phenotype but now in a very short time a large assortment of different treatment options for prophylaxis have become/are becoming available and the haemophilia community will need to determine how to best use these recognizing that no 'one treatment fits all'. [ABSTRACT FROM AUTHOR]

Introduction: Damoctocog alfa pegol (BAY 94‐9027, Jivi®) is an approved extended half‐life factor VIII (FVIII) for treatment of previously treated patients with haemophilia A aged ≥12 years. We report the final results of an interventional, post‐marketing study of damoctocog alfa pegol prophylaxis in patients with severe haemophilia A. Methods: In this open‐label, interventional, post‐marketing, phase 4 trial (NCT04085458), previously FVIII‐treated patients with severe haemophilia A aged ≥18 years received damoctocog alfa pegol for ≥100 exposure days (EDs). Patients initially received 45 IU/kg every 5 days (recommended) or 40 IU/kg twice‐weekly. At Visit 3, patients' doses could be increased, or treatment frequency adapted. The primary endpoint was FVIII inhibitor development (titre ≥.6 Bethesda units). Secondary endpoints included anti‐polyethylene glycol (PEG) antibody development, treatment‐emergent adverse events (AEs) and annualized bleeding rate (ABR). Results: Overall, 36 patients were enrolled; 32 patients received treatment, of whom, 27 completed the study. No patients developed FVIII inhibitors; three tested transiently positive for low‐titre anti‐PEG antibodies without clinical relevance. Three patients reported study‐drug‐related AEs of mild or moderate intensity. Two patients discontinued the study due to AEs. No deaths occurred. Most patients (70%) were treated with E5D/E7D regimens. The median (Q1;Q3) total ABR (N = 30) was 3.0 (.0;9.0) pre‐study and 1.8 (.7;5.9) during the study. Conclusion: Damoctocog alfa pegol individualized prophylaxis regimens were well‐tolerated with no immunogenicity concerns. ABRs improved following the switch from pre‐study prophylaxis to damoctocog alfa pegol prophylaxis. These results support the favourable safety and efficacy profile of damoctocog alfa pegol prophylaxis. [ABSTRACT FROM AUTHOR]

Aim: Joint damage due to haemarthrosis can be effectively monitored with point‐of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD‐US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed. Methods: The databases of two observational, cross‐sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality. The HEAD‐US score was calculated in both studies by the same trained operators. Results: Overall, 95 HA and 41 HB severe patients were included, with a mean age of 35.2 ± 11.8 and 32.7 ± 14.2 years, respectively. The percentage of patients who received prophylaxis, over on‐demand (OD) treatment, was much higher in HA (91.6%) than in HB (65.8%) patients. With a similar number of target joints, the HEAD‐US score was zero in 6.3% HA and 22.0% HB patients (p <.01), respectively. The HA population showed significantly worse HEAD‐US scores. Whilst osteochondral damage occurred more frequently in patients OD or tertiary prophylaxis, our data suggest that articular damage is less prominent in primary/secondary prophylaxis, regardless of the type of haemophilia. These latter treatment modalities were also associated with a lower prevalence of synovial hypertrophy, particularly in HB patients. Conclusion: This post hoc analysis indicates that joint status seems to be significantly influenced by haemophilia type (HA or HB) and treatment modality in these severe Spanish populations with severe disease. Continuing HEAD‐US monitoring for the early detection and management of intra‐articular abnormalities, as well as more efficiently tailored therapies should be warranted. [ABSTRACT FROM AUTHOR]

Introduction: The impact of moderate haemophilia on health‐related quality of life (HRQoL) and physical activity (PA) is not well known. In previous studies, persons with factor VIII/factor IX activity (FVIII/FIX:C) below 3 IU/dL were associated with a more severe bleeding phenotype than predicted. Aim: To explore HRQoL and PA in patients with moderate haemophilia A (MHA) and B (MHB). Methods: A cross‐sectional, multicentre study covering patients with MHA and MHB in Sweden, Finland, and Norway. HRQoL was assessed with the EuroQoL 5‐Dimensions (EQ‐5D) form and PA with the International Physical Activity Questionnaire among participants aged ≥15 years. Results: We report on 104 patients aged 15–84 years from the MoHem study. Overall, EQ‐5D utility was.85 (median) (Q1–Q3 0.73–1.0) with corresponding visual analogue scale (VAS) 80 (70–90), which were similar regardless of treatment modality, FVIII/FIX:C, and MHA or MHB. Pain and mobility were most frequently affected dimensions. Utility (r = ‐.54), VAS (r = ‐.42), and PA (r = ‐.32) correlated negatively with arthropathy (HJHS). Only patients aged 41–50 years displayed lower utility (p =.02) and VAS (p <.01) than the Norwegian population norm. Patients on prophylaxis aged 35–54 years reported higher PA than those treated on‐demand (p =.01). Conclusion: Haemophilic arthropathy had negative impact on HRQoL and PA in Nordic patients with moderate haemophilia. Middle‐aged patients captured lower utility and VAS than observed in the general population. Tailored prophylaxis and improved joint health may influence positively on HRQoL and PA also in moderate haemophilia. [ABSTRACT FROM AUTHOR]

Background: Hereditary thrombotic thrombocytopenia purpura (hTTP) is an ultra‐rare disorder resulting from an inherited deficiency of ADAMTS13, a von Willebrand factor (VWF)‐cleaving metalloprotease. The plasma‐derived factor VIII/VWF Koate (FVIII/VWFKoate) has been shown to contain ADAMTS13, allowing for its use to treat hTTP at home by the patient/caregiver. Aim: Based on prior demonstration of safe and effective use of FVIII/VWFKoate in eight patients with hTTP, we conducted a retrospective study to gather additional data regarding the use of FVIII/VWFKoate for hTTP. Methods: This was a multicentre, retrospective, noninterventional chart review of patients who had received FVIII/VWFKoate for the management of hTTP. Data collected included demographics, medical history, relevant family history, past use and tolerability of fresh frozen plasma, and details regarding FVIII/VWFKoate therapy. Results: The cohort included 11 patients (seven males, four females) with hTTP, ranging in age at study entry from 2 to 28 years. The average duration of FVIII/VWFKoate therapy was 4.8 years (range, 0.5–6.5 years). Among nine patients using FVIII/VWFKoate as prophylaxis, the normalized annual rate of breakthrough TTP episodes ranged from 0.2 to 1.1 episodes/year. All nine patients who received FVIII/VWFKoate prophylaxis had thrombocytopenia recorded at baseline, while eight (88.9%) did not have thrombocytopenia after using FVIII/VWFKoate. There was one AE (unspecified) attributed to FVIII/VWFKoate. Conclusion: These data suggest that FVIII/VWFKoate is a safe and well‐tolerated source of the missing ADAMTS13 enzyme in patients with hTTP, producing a marked reduction in thrombocytopenia prevalence, low frequency of TTP episodes, and with the added benefit of self‐ or caregiver‐administration. [ABSTRACT FROM AUTHOR]

Introduction: The standard of care in severe haemophilia A is prophylaxis, which has historically aimed for a factor VIII (FVIII) trough level of ≥1%. However, despite prophylactic treatment, people with haemophilia remain at risk of bleeds that have physical and quality of life implications, and that impact everyday life. Aim: The aim of this review was to evaluate evidence supporting the relationship between targeting higher FVIII activity levels with prophylaxis and improved outcomes in people with haemophilia A. Methods: We conducted a narrative review that defined the unmet needs and treatment goals in people with haemophilia A, evaluated evidence to support targeting higher FVIII activity levels, and highlighted therapies that may support higher and sustained FVIII activity levels and improved outcomes for people with haemophilia A. Results: Despite recent advances in treatment, unmet needs remain, and people with haemophilia continue to experience joint and functional impairment, acute and chronic pain, and poor mental health. All these negatively impact their health‐related quality of life. Evidence suggests that FVIII activity levels of up to 50% may be needed to achieve a near‐zero joint bleed rate. However, achieving high FVIII activity levels with current standard and extended half‐life (EHL) FVIII replacement therapies is associated with a high treatment burden. Innovative treatment options may provide high sustained FVIII activity levels and improved patient outcomes. Conclusion: Evidence suggests that FVIII activity levels in people with haemophilia A should be sustained at higher levels to improve joint and patient outcomes and enable progression towards health equity. [ABSTRACT FROM AUTHOR]

Introduction: Extended half‐life (EHL) factor VIII and IX concentrates as prophylaxis against bleeds have been available to selected persons with haemophilia (PWH) in Australia since March 2018. Preliminary analysis of switching to EHL demonstrated increased treatment adherence, fewer injections and improved bleeding outcomes. Aims: To characterise clinical practices regarding the use of EHL in Australia, to further evaluate treatment regimens and bleeding outcomes, and to analyse the influence of EHL product pharmacokinetics on clinical decision‐making. Methods: A national, retrospective study was conducted using the Australian Bleeding Disorders Registry (ABDR). Patients on EHL products during the entire 2019 calendar year were included for analysis. Results: A complete and validated dataset of 174 PWH was analysed, 115 Haemophilia A (HA) and 59 Haemophilia B (HB). Adherence to EHL therapy was 85.7% in HA and 87.2% in HB. About 63.5% of HA and 64.4% of HB PWH reported zero spontaneous bleeds over 12months. Ankles were the most frequent spontaneous bleed site. Approximately one‐third patients underwent dose adjustments, with most frequent reasons being pharmacokinetics, body weight change and breakthrough bleeds. About 19.5% of PWH had target joint history, with spontaneous bleeds reported in 58% of that cohort on EHL. Multivariate regression showed significant impact of non‐adherence, target joint history and short half‐life on spontaneous bleeds in the HA cohort; however only short half‐life had significant impact in the HB cohort. Conclusion: EHL usage in Australia shows excellent treatment adherence and bleeding outcomes. This study affirms the use and value of widely available population‐based pharmacokinetics as a clinical tool. [ABSTRACT FROM AUTHOR]

AimPhase 2b study to assess efficacy, safety, thrombogenicity, immunogenicity and tolerability with 28 days of daily dosing of subcutaneous (SQ) dalcinonacog alfa as prophylaxis for haemophilia B (HB).MethodsAdult males with a confirmed diagnosis of congenital HB (factor IX [FIX] activity

Introduction: The real‐world effectiveness of the efmoroctocog alfa (recombinant FVIII Fc fusion protein, a rFVIIIFc) has been investigated in numerous studies, however, currently, there exists no comprehensive collection of the existing real‐world evidence (RWE) on the performance of prophylactic use of rFVIIIFc. Aim: The aims of this systematic literature study were to identify, review, evaluate and collate the RWE of prophylactic rFVIIIFc for patients with haemophilia A reported in Europe. Methods: We searched Medline and Embase from 2014 to February 2022 to identify publications reporting the effectiveness of rFVIIIFc in patients with haemophilia A. The outcomes of interest were annualised bleeding rates (ABR, AjBR, AsBR), injection frequency, factor consumption, adherence, development of inhibitors and quality‐of‐life measures. Results: 46 eligible publications (eight full‐text articles) were included. rFVIIIFc showed a low ABR in patients with haemophilia A. Studies assessing treatment switching from a standard half‐life (SHL) treatment to rFVIIIFc found that the ABR and consumption were reduced in most patients. Studies assessing rFVIIIFc effectiveness reported a median ABR between 0.0 and 2.0 with median injections per week ranging between 1.8 and 2.4 and median doses between 60 and 105 IU/kg/week. Of the studies assessing inhibitor development, only one study reported an incidence of a low titre inhibitor, and no patients developed clinically significant inhibitors. Conclusion: rFVIIIFc prophylaxis treatment results in a low ABR across studies in patients with haemophilia A in a European real‐world setting, which correlates with findings from clinical trials assessing the efficacy of rFVIIIFc in patients with haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: 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. Aims: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: The NuProtect study reported data on the immunogenicity, efficacy and tolerability of simoctocog alfa (Nuwiq®) in 108 previously untreated patients with severe haemophilia A planned to be treated for ≥100 exposure days or up to 5 years. The NuProtect‐Extension study collected long‐term prophylaxis data in children with severe haemophilia A. Methods: Patients who completed the NuProtect study according to the protocol were eligible for the NuProtect‐Extension study, a prospective, multinational, non‐controlled, Phase 3b study. Results: Of 48 patients who entered the extension study, 47 (median age 2.8 years) received prophylaxis with simoctocog alfa for a median of 24 months, with 82%–88% on a twice‐weekly or less regimen. No patient developed FVIII inhibitors during the extension study. The median (IQR) annualized bleeding rate (ABR) during prophylaxis was 0 (0–0.5) for spontaneous bleeding episodes (BEs) and 1.00 (0–1.95) for all BEs. ABRs estimated using a negative binomial model were.28 (95% CI:.15,.53) for spontaneous and 1.62 (95% CI: 1.09, 2.42) for all BEs. During the median follow‐up of 24 months, 34 (72%) patients had zero spontaneous BEs and 46 (98%) had zero spontaneous joint BEs. Efficacy in treating BEs was excellent or good for 78.2% of rated BEs, and efficacy of surgical prophylaxis was excellent for two rated surgeries. No treatment‐related adverse events were reported. Conclusion: No FVIII inhibitors developed during long‐term prophylaxis in the NuProtect‐Extension study. Prophylaxis with simoctocog alfa was efficacious and well‐tolerated, and is therefore an attractive long‐term option for children with severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. Aim: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). Methods: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in‐person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. Results: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. Conclusion: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia B patients with factor IX inhibitors have particularly unmet needs for conventional therapy. Aim: Phase II/III clinical trial, multicentre, open‐label, prospective, self‐controlled study was conducted to assess MC710 prophylaxis in haemophilia B patients with inhibitors. Methods: We enrolled haemophilia patients who had received episodic or prophylactic treatment with bypassing agents up to that time. The participants continued their conventional therapy for 24 weeks and then MC710 was prophylactically infused intravenously every 2 or 3 days at 60 to 120 μg as FVIIa per kilogram of body weight for 24 weeks. The primary endpoint was the annual bleeding rate (ABR) requiring bypassing agents, which was compared intraindividually between the conventional therapy period and the MC710 prophylaxis period. Results: A total of 11 male haemophilia B patients were enrolled. The median ABR ratio for each participant (the prophylaxis period ABR divided by the conventional therapy period ABR) was.33 (2.1/6.5), range from.00 to 3.77. ABR ratios for 9 of the 11 patients ranged from.00 to.60, and 3 of the 9 patients had zero bleeding events during the prophylaxis period. Meanwhile, ABR ratios for the remaining two patients were 2.53 and 3.77, respectively. Although a fibrinogen decrease recovered by the dose reduction was reported for only one participant as the sole adverse drug reaction in this study, no thrombotic events or other safety concerns were reported. Conclusion: MC710 prophylaxis is considered to be decrease the bleeding rate in haemophilia B patients with inhibitors without safety concerns. [ABSTRACT FROM AUTHOR]

Introduction: Majority of haemophilia A patients in our comprehensive care centre have switched from standard half‐life (SHL) to extended half‐life (EHL) FVIII products in a short time. Aim: We compared the clinical and laboratory outcomes between SHL and EHL FVIII prophylaxis in product switchers. Methods: This is a retrospective inception cohort of all adult haemophilia A patients switched to EHL (rFVIIIFc or rFVIII‐PEG) prophylaxis in our centre. Dosing, product utilization, annualized bleed rates (ABR), treatment regimen and pharmacokinetics by Web Accessible Population Pharmacokinetic Service (WAPPS)‐Hemo were compared between SHL and EHL. Results: We included 38 patients, whose median age was 38 years (range 17–75). Median FVIII dose was 23 IU/kg for SHL versus 25 IU/kg for EHL. After switching, weekly infusions decreased by 29% from median 2.8 (every 2.5 days) to 2.0 (every 3.5 days) (P = <.001) and factor consumption for prophylaxis by 17% from 60 to 50 IU/kg/week (P = <.001). Weekly infusions decreased in 71% and FVIII utilization in 55% of patients. ABR remained low (1.0 for SHL and.5 for EHL, respectively). In pharmacokinetics, the half‐life of FVIII increased from median 13 to 21 h after switching. Times above.01 and.03 IU/ml improved from 85 to 131 h and from 65 to 106 h. Half‐lives of the SHL products and von Willebrand factor levels predicted half‐lives with the EHL products. Conclusions: Our cohort study confirms the successful experience of switching to EHL FVIII products, with decreased infusion frequency, factor consumption and excellent clinical efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Current treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma‐derived FVIII is short in China. Purpose: To evaluate the efficacy and safety of a new B‐domain deleted (BDD) recombinant FVIII (TQG202) produced by human‐derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha. Methods: This multicentre, clinical trial consisted of an open‐label, randomized, two‐period cross‐over trial assessing single‐dose pharmacokinetics (PK), and a single‐arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single‐dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded. Results: Twenty‐six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2–2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was.027 (95% CI:.026–.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors. Conclusion: TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Emicizumab prophylaxis significantly reduces bleeding events; however, the associated impact on bone/joint health is unknown. Aim: To explore the effect of emicizumab prophylaxis on bone/joint health in people with haemophilia A (PwHA) without FVIII inhibitors enrolled in HAVEN 3 (NCT02847637). Methods: Haemophilia joint health scores (HJHS; v2.1) were evaluated at baseline and Weeks 49 and 97 in PwHA receiving emicizumab (n = 134), and at baseline and Weeks 49, 73 and 97 in PwHA who switched to emicizumab after 24 weeks of no prophylaxis (n = 17). Bone and joint biomarkers were measured in 117 PwHA at baseline and at Weeks 13, 25, 49 and 73. Results: HJHS was lower for PwHA who were previously on FVIII prophylaxis, aged <40 years or had no target joints at baseline compared with PwHA who were receiving no prophylaxis, aged ≥40 years or with target joints. Clinically significant mean (95% confidence interval) improvements from baseline of −2.13 (−3.96, −.29) in HJHS joint‐specific domains were observed at Week 49 in PwHA with at least one target joint at study entry (n = 71); these changes were maintained through Week 97. Improvements in HJHS from baseline were also observed for PwHA aged 12–39 years. Biomarkers of bone resorption/formation, cartilage degradation/synthesis, and inflammation did not change significantly during emicizumab prophylaxis. Conclusions: Clinically relevant improvements in HJHS were observed in younger PwHA and those with target joints after 48 weeks of emicizumab in HAVEN 3. Biomarkers of bone/joint health did not show significant changes during 72 weeks of emicizumab prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: As standard care of severe haemophilia A (SHA), prophylaxis should be individualised. Aim: This study aimed to investigate the effectiveness of this new‐proposed individualised prophylaxis protocol. Methods: Boys with SHA were enrolled and followed a PK‐guided, trough‐level escalating protocol of prophylaxis after a six‐month observational period. In the next 2 years, clinical assessments including joint bleeds, ultrasound (US) scores and Haemophilia Joint Health Score (HJHS) in both sides of ankles, knees and elbows were conducted every 6 months as a scoring system, which determined whether the trough level's escalation. Adjustment of dosing regimen was based on WAPPS‐Hemo. Results: Fifty‐eight SHA boys were finally analysed. Their age and bodyweight were 5.3(2.8,6.9) years and 21.5(16,25) kg. During the study, 47 escalations were conducted. At study exit, the patient number and proportion of different trough level groups were: < 1 IU/dl, 17.2% (10/58); 1–3 IU/dl, 53.5% (31/58); 3–5 IU/dl, 15.5% (9/58); > 5 IU/dl, 13.8% (8/58). Significantly reduced annualised bleeding rate [4(0,8) to 0(0,2), p <.0001] and annualised joint bleeding rate [2(0,4) to 0(0,.25), p <.0001] was observed at study exit as well as the continuous trend of increased zero bleeding proportion (ZBP) (27.6%–69.0%) and zero joint bleeding proportion (46.5%–81.3%). Besides, 85% (6/7) of the target joints vanished. Statistical improvements of US scores (p =.04) and HJHS (p =.02) were also reported at study exit. Conclusion: Our results showed the effectiveness of our protocol based on individualised target trough level and emphasise the importance of personalised prophylaxis. [ABSTRACT FROM AUTHOR]

Introduction: Omfiloctocog alfa, the first China‐developed recombinant factor VIII (FVIII), demonstrated efficacy and safety of prophylaxis in previously treated patients (PTPs) aged ≥12 years with severe hemophilia A in China. Aims: To investigate efficacy, safety and pharmacokinetics (PK) of omfiloctocog alfa in pediatric PTPs with severe hemophilia A in China. Methods: PTPs (>50 exposure days [ED] for Chinese patients aged <6 years; >150 EDs for patients aged 6–12 years) were treated with omfiloctocog alfa at 25–50 IU/kg every other day or three times per week for 24 weeks. PK was evaluated after single injection of 50 IU/kg. The primary efficacy endpoint was annualized bleeding rate (ABR). Results: A total of 69 patients were enrolled (<6 years, n = 35; 6–12 years, n = 34) and mean exposure to omfiloctocog alfa was 78.9 days. Mean half‐life was 6.7 and 10.2 h in children < 6 years and 6–12 years, respectively. Estimated mean ABRs of all patients were 4.05 for overall bleeding episodes and 1.38 for spontaneous bleeding episodes. Of 127 bleeding episodes, the success rate was 92.1%. 39.7% patients did not experience any bleeding episodes and the mean weekly dose of FVIII was 109.1 IU/kg for these patients. 83% bleeding episodes were controlled with ≤2 injections. Adverse reactions occurred in 2.9% of the patients. One 2‐year‐old patient developed inhibitors after 12 EDs and it resolved with omfiloctocog alfa immune tolerance induction. Conclusion: Omfiloctocog alfa was efficacious and well tolerated for the prevention and treatment of bleeding in Chinese pediatric PTPs with severe hemophilia A. [ABSTRACT FROM AUTHOR]

Background: Inhibitor‐development is a serious complication in patients with haemophilia (PwH). Previous studies reported that therapeutic and genetic factors could be associated with these alloantibodies. Relevant clinical features such as genetic‐background and different treatment regimens in Japan remain unclear, however. Aims: To analyse a nation‐wide Japanese registry for PwH, and to examine risk factors for inhibitor‐development. Methods and results: Newly diagnosed patients with haemophilia A (PwHA) or haemophilia B (PwHB) without inhibitors after 2007, and with treatment records traceable from 0 to 75 exposure days (ED), were enrolled in the Japan Hemophilia Inhibitor Study 2 (J‐HIS2) initiated in 2008. Of 417 patients (340 PwHA, 77 PwHB) from 46 facilities, 83 (76 PwHA, 7 PwHB) were recorded with inhibitors by July 2020. Inhibitors were observed in 31.0% of severe PwHA, 8.0% moderate and 1.6% mild and in 17.1% of severe PwHB. The majority of inhibitors (89.7% in severe PwHA and 71.4% in severe PwHB) were detected on or before 25ED (median 12ED in PwHA and 19ED in PwHB). Genotyping in these severe patients identified an association between inhibitor‐development and null variants of F8 (P <.01) or F9 (P <.05). A lower incidence of inhibitors was recorded in severe PwHA treated with prophylaxis than in those treated on‐demand (P <.01). A past‐history of intracranial‐haemorrhage appeared to be associated with inhibitor‐development, while FVIII‐concentrates infusion and routine vaccination on the same day was not related to inhibitor‐development. Conclusion: The J‐HIS2 study has identified significant clinical variables associated with inhibitor‐development in Japanese PwH, consistent with other global studies. [ABSTRACT FROM AUTHOR]

Background: Prophylactic treatment is the gold standard in the treatment of patients with haemophilia. Prophylaxis with extended half‐life (EHL) treatment has shown long‐term safety and efficacy in patients with haemophilia. Aim: To evaluate the efficacy of prophylaxis with EHL treatment in the frequency of haemarthrosis and musculoskeletal health in adult patients with severe haemophilia A. Methods: Prospective cohort study. Forty‐six patients with severe haemophilia A were recruited. The frequency of haemarthrosis (self‐reports), joint condition (Haemophilia Joint Health Score), pain intensity (visual analogue scale), range of motion (goniometry), and strength (dynamometry) and muscle activation (surface electromyography) were evaluated. Three assessments were carried out: at baseline (T0), at 6 months (T1) and at 12 months following treatment (T2). Results: There were significant changes in the within‐subject effect in the frequency of haemarthrosis in elbow (F(1.05;96.20) = 3.95; P <.001) and knee (F(1.73;157.99) = 9.96; P <.001). Significant within‐subject effect in elbow pain intensity (F(2;182) = 63.51; P <.001) was found. The mean values of the frequency haemarthrosis in elbow (from.66±1.01 to.04±.20) and knees (from.55±.68 to.33±.53) decrease after the period study. The intensity of elbow pain and (from 3.08±1.69 to 2.67±1.73), decrease after the 12‐month follow‐up period. Conclusions: Prophylaxis with extended half‐life treatment reduces the frequency of haemarthrosis in elbow and knee in adult patients with haemophilia. EHL treatment reduces the intensity of elbow pain in patients with haemophilic arthropathy. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia has substantial SD effects on health‐related quality of life (HRQoL), particularly for people with severe haemophilia. How certain aspects of haemophilia influence HRQoL is not well understood. Aim: To develop predictive models of variables influencing HRQoL in people with severe haemophilia A or B. Methods: We used data from 514 participants with haemophilia A or B who provided EQ‐5D‐3L responses in the 2015 CHESS study. Treatment was categorized as always been on‐demand (POD), previously on prophylaxis and moved to on‐demand regimen (SOD), on prophylaxis from diagnosis (PX), and prophylaxis, previously on‐demand (PXOD). Target joints were defined as 'locations of chronic synovitis' as reported by the treating physician. Regression models were evaluated to assess the impact of demographic and clinical covariates on HRQoL scores. Results: Significant covariates were generally consistent across models, with number of target joints, number of hospital admissions, and any haemophilia treatment regimen other than PX all independently negatively impacting estimated EQ‐5D score. Higher level of treatment adherence (high vs. low/medium) and use of a prophylaxis treatment regimen had positive effects on estimated EQ‐5D scores. Target joints were associated with a 0.04 decrement in EQ‐5D score, and high versus low/medium adherence was associated with a 0.06 increment. PXOD, POD, and SOD treatment regimens were associated with decrements in predicted scores of 0.07, 0.09, and 0.08, respectively, versus PX. Conclusion: This study provides a model to estimate the impact of haemophilia interventions on HRQoL, to help assess the relative impact on patient‐centric outcomes for this lifelong condition. [ABSTRACT FROM AUTHOR]

Background: Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long‐term prophylaxis. Aim: Systematically summarize the evidence on the clinical outcomes of secondary long‐term prophylaxis in patients with VWD and severe recurrent bleedings. Methods: We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long‐term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non‐Randomized Studies of interventions (ROBINS‐I) tool to assess the quality of the included studies. We conducted random‐effects meta‐analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR],.24; 95% confidence interval [CI],.17–.35; low certainty evidence), and of epistaxis (RR,.38; 95%CI,.21–.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI.12–59.57; low certainty). Evidence from four before‐and‐after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR.34; 95%CI,.25–.46; very low certainty evidence). Conclusion: VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits. [ABSTRACT FROM AUTHOR]

Introduction: The B‐Natural study is a multicentre, multinational, observational study of haemophilia B (HB) designed to increase understanding of clinical manifestations, treatment and quality of life (QoL). Aim: To characterise and compare QoL in HB across disease severity groups and individuals with inhibitors to identify gaps in treatment. Methods: A total of 224 individuals from 107 families were enrolled from a total of 24 centres in North America (n = 16), Europe (n = 7) and Asia (n = 1). Of these, 68 (30.4%) subjects had severe (<1 IU/dL), median age 15.6 years, 114 (50.9%) moderate (1–5 IU/dL), age 13.3 years, and 42 (18.8%) mild (>5–< 40 IU/dL), age 12.1 years, disease. Twenty‐nine participants had inhibitors or a history of inhibitors. Three versions of the EQ‐5D instrument were used as a measure of QoL: proxy (ages 4–7), youth (ages 8–15) and self (age 16+). Each instrument included a visual analogue scale ranging from 100 (best health) to 0 (worst health) to assess current day's health (EQ VAS). Range‐of‐motion (ROM) for elbows, knees and ankles was assessed using a four‐point scale, from which a composite score was calculated. Results: In all severity groups, a proportion of subjects showed less than optimal QoL. The majority of the mild and moderate severe participants reported a normal EQ‐5D health profile (79% and 72%, respectively), whereas about half (47%) of the severe participants and only 13% of the inhibitor participants reported this profile. Conclusion: The B‐Natural study reveals impacted QoL in all disease severities of HB including those with inhibitors. Unmet needs remain and include nonsevere HB. [ABSTRACT FROM AUTHOR]

Introduction: Haemophilia management and patients' quality of life significantly improved. However, data on current patients', caregivers' and clinicians' satisfaction and limitations of treatments and haemophilia management are limited. Aim: Assessing the management satisfaction and unmet needs from the perspective of Italian patients with haemophilia (PWH) without inhibitors (or caregivers if children) and of specialist physicians. Methods: Surveys (for patients≥18 years, caregivers of children and haemophilia specialists) were developed by a multidisciplinary working group and conducted from November 2019 to June 2020. Results: Among 275 participants, 120 (43.6%) were PWH without inhibitors, 79 (28.7%) caregivers and 37 (13.4%) clinicians. Patients and caregivers perceived a higher control of the disease compared to clinicians. However, more than 40% of patients and caregivers reported to feel significantly conditioned by the risk of bleeding during their daily life. PWH reported a 6‐month mean/median (range) of bleeds 2.3/.0 (0‐24) and caregivers 1.3/.0 (0‐16) in children. The treatment burden (frequency of administration) was not satisfactory for more than half adults and caregivers of children treated with prophylaxis. A good access to treatment, haemophilia centres and medical service was reported, with issues associated to the multidisciplinary approach and treatment at emergency department. Conclusions: This large national study provides an updated overview of haemophilia care in Italy from different points of views, highlighting positive aspects and unmet needs. This information can guide future interventions to improve haemophilia management and the assessment of impact of new treatment options. [ABSTRACT FROM AUTHOR]

Introduction: The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy. Aim: The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions. Methods: The survey was conducted in late 2020/early 2021 in 18 centres representing 17 countries in the Europe/Middle East region treating a total of 4955 patients, and included sections specific to patient and centre demographics, treatment protocols (both ITI and prophylactic), inhibitor development and initiation of ITI, treatment success, and the incidence of adverse events. Results: While our results indicate that ITI can still be considered a mainstay of treatment for patients with HA with inhibitors, less than daily dosing of ITI in combination with emicizumab prophylaxis is becoming commonplace across the spectrum of disease severity, with initiation being guided by bleeding patterns. The most frequently cited reasons for not initiating emicizumab prophylaxis were availability or reimbursement issues. Conclusion: ITI remains a mainstay for haemophilia treatment of patients with HA with inhibitors, but emicizumab has become a preferred first‐line approach to protect against bleeds and represents an alternative to burdensome ITI in certain patient groups. [ABSTRACT FROM AUTHOR]

Introduction: Turoctocog alfa (NovoEight®) is a B‐domain‐truncated recombinant factor VIII (FVIII) approved for patients with haemophilia A. Aim: To investigate the long‐term safety and efficacy of turoctocog alfa in routine clinical practice. Methods: Guardian 5 was a prospective, multinational, non‐interventional, post‐authorisation safety study. Male previously treated patients (> 150 exposure days [EDs]) of any age with severe/moderately severe haemophilia A (FVIII ≤ 2%) and a negative inhibitor test prior to first dosing (independent of FVIII‐inhibitor history) were included to receive prophylaxis or on‐demand treatment. The primary endpoint was the proportion of patients developing FVIII inhibitors (≥.6 Bethesda Units [BU]) after baseline visit, measured as per routine practice of each study site during clinic visits. Secondary endpoints included haemostatic effect, annualised bleeding rate (ABR), and adverse reactions assessment. The study concluded when 50 patients reached 100 EDs/patient minimum. Results: Seventy patients were screened and 68 exposed to turoctocog alfa; 63 (92.6%) were on prophylaxis and five received on‐demand treatment. Six (8.8%) patients reported a history of positive inhibitors. During the study, patients were exposed to turoctocog alfa for a mean (standard deviation) of 131.9 (99.0) days/patient. Fifty‐five of 58 patients who completed the study were tested for FVIII inhibitors; no positive tests were reported. Overall success rate of turoctocog alfa for treatment of bleeds was 87.3%. Among patients receiving prophylaxis, median (range) ABR was 1.97 (.0–25.5) bleeds/year; estimated ABR (negative binomial model) was 3.65 (95% confidence interval: 2.53–5.25). Conclusion: Turoctocog alfa was safe and efficacious for haemophilia A treatment in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Challenges with personalised prophylaxis in haemophilia remain, including designing unique dosing schedules that require continual adjustments and monitoring using complex sampling procedures. Aim: To assess long‐term efficacy and pharmacokinetic outcomes with fixed‐dose N8‐GP prophylaxis. Methods: Descriptive analyses were performed on data from the pathfinder 2 and pathfinder 5 trials of patients with severe haemophilia A. Bleed frequency and reoccurrence were assessed in relation to several clinical criteria of interest. Bleed risk relative to time since last dose was assessed using calculated annualised bleeding rate (ABR). Long‐term ABR and mean factor VIII (FVIII) trough levels were assessed in patients who received consistent N8‐GP prophylaxis every 4 days (Q4D). Results: During pathfinder 2, 117/136 patients with study‐drug exposure of ≥600 days experienced bleeding episodes; 8.6% of bleeds were reoccurring bleeds; bleed reoccurrence decreased over time. For patients who received consistent Q4D prophylaxis across the trial (n = 61), mean ABR decreased from 3.5 bleeds/year (Year 1) to 1.6 bleeds/year (Year 6); mean FVIII trough levels stabilised at approximately 5% (Year 6). Across patients who received prophylaxis at some point during pathfinder 2 (n = 177), 125/126 (99%) reoccurring bleeds were joint bleeds. For patients receiving Q4D prophylaxis, bleeding risk generally increased as the time since the last prophylaxis dose increased. A similar reduction in ABR and stabilisation of trough level was observed in pathfinder 5. Conclusion: Long‐term exposure (> 5 years) to fixed‐dose N8‐GP prophylaxis resulted in a protective haemostatic effect, with reduction in bleed frequency and reoccurrence, and stabilisation of FVIII trough level over time. [ABSTRACT FROM AUTHOR]

Background: Patients with severe haemophilia have impaired haemostatic response, delayed clot formation and fibrin clots that are vulnerable to fibrinolysis. Emicizumab is a bispecific antibody that mimics activity of activated factor VIII (FVIII) and increases haemostatic capacity to the level of moderate‐to‐mild haemophilia, thereby used for prophylaxis. Regardless of the impressive clinical performance of emicizumab, breakthrough bleeds may still occur. We aimed to study, in FVIII knockout mice (FVIII‐KO), whether haemostasis is improved with the addition of tranexamic acid (TxAc) to emicizumab. Methods: FVIII‐KO mice received prophylaxis with emicizumab or emicizumab+TxAc before trauma. FVIII‐KO mice were given emicizumab 1.5 mg/kg via IV injection. A second retro‐orbital IV injection containing human FIX and FX (both 100U/kg) was given 24 h later and 5 min before the tail amputation or knee trauma. After trauma‐induced knee joint bleeding, magnetic resonance imaging (MRI), and histological analysis were used to compare haemostatic efficacy of the two prophylactic strategies. Thrombin generation (TG) was measured and clots obtained with TG experiment were analysed by scanning electron microscopy. Results: In FVIII‐KO mice, blood loss after tail clip was lower after prophylaxis with emicizumab+TxAc compared to emicizumab. MRI results and histological analysis of knee joints showed that the addition of TxAc significantly decreased joint bleeding. Fibrin fibre diameters of mice treated with emicizumab only was thicker than those who received combined prophylaxis with emicizumab+TxAc. Conclusion: Our results suggest a potential benefit of TxAc when used in combination with emicizumab in prophylactic settings, especially in patients presenting breakthrough bleeds. [ABSTRACT FROM AUTHOR]

Introduction: For children with haemophilia, early initiation of prophylaxis is crucial to prevent life‐threatening bleeds and maintain joint health throughout life. Options for prophylaxis have recently increased from replacement therapy with standard or extended half‐life coagulation factor products to include other haemostasis products, such as the non‐replacement therapy emicizumab. Aim: To review key factors that determine the choice of prophylaxis in young children. Methods: Key clinical questions on the implementation of prophylaxis for haemophilia in children were identified and PubMed was searched for evidence supporting guidance on the implementation of prophylaxis. Results: The results of the literature search and the practical experience of the authors were used to build consensus on when to start prophylaxis, the pros and cons of the products available to guide the choice of product, and practical aspects of starting prophylaxis to guide the choice of regimen. Conclusions: In this era of increasing therapeutic choices, available information about the range of treatment options must be considered when initiating prophylaxis in young children. Parents or care givers must be sufficiently informed to allow informed shared decision making. Although plentiful data and clinical experience have been gathered on prophylaxis with clotting factor replacement therapy, its use in young children brings practical challenges, such as the need for intravenous administration. In contrast, our relatively brief experience and limited data with subcutaneously administered non‐replacement therapy (i.e., emicizumab) in this patient group imply that starting emicizumab prophylaxis in young children requires careful consideration, despite the more convenient route of administration. [ABSTRACT FROM AUTHOR]

Keywords: FXIII deficiency; home treatment; prophylaxis; quality of life; self-infusion EN FXIII deficiency home treatment prophylaxis quality of life self-infusion e649 e653 5 09/16/21 20210901 NES 210901 Hereditary factor XIII (FXIII) deficiency (FXIIID) is a rare disease (prevalence of 1:2-5 million persons), inherited in a recessive autosomal pattern, due to homozygous or heterozygous compound mutations.1 Since FXIII is a clot-stabilizing transglutaminase, FXIIID not only results in spontaneous late bleeding and menorrhagia but also has a particularly high risk of spontaneous intracranial haemorrhage (30% or more, in the first two decades of life).1,2 Then accurate diagnosis and early start of prophylaxis with intravenous infusion of FXIII concentrate are the key to guarantee a normal life.1-4 In 2016, there were 64 people with FXIIID registered in the Brazilian Ministry of Health (prevalence of 1:3 million inhabitants), 11 (17%) of whom were treated at the public reference service called Blood Treatment Centre of the state of Minas Gerais (HEMOMINAS). Since the start of prophylaxis, 5/9 and 3/9 patients reported spontaneous or post-traumatic bleeding which required FXIII infusion, respectively. Although FXIII prophylaxis was started 2 years or less after diagnosis in five patients, two patients started prophylaxis after 16 and 17 years from the date they were informed about the disease. [Extracted from the article]

Introduction: Recombinant factors VIII and IX Fc (rFVIIIFc/rFIXFc) became available in Canada in 2016 and were the only extended half‐life (EHL) factor concentrates available in Canada until 2018. Objectives: We aim to describe the change in product utilization in Canadians who switched to rFVIIIFc/rFIXFc. Methods: This prospective and retrospective cohort study enrolled males aged ≥6 years with moderate or severe haemophilia who switched to rFVIIIFc/rFIXFc and those who remained on standard half‐life (SHL) between 2016 and 2018. Factor utilization and annualized bleeding rates (ABR) were collected at baseline, 1‐year and 2‐years. Due to low prospective enrolment (n = 25 switchers), prospective and retrospective data were pooled. Results: 125 switchers (93 rFVIIIFc, 32 rFIXFc) and 33 non‐switchers were included. The median age was 17 (rFVIIIFc) and 38 years (rFIXFc). Prior to switch, over 80% were on prophylaxis. There was a statistically significant reduction in the prescribed weekly prophylactic dose after the switch to rFVIIIFc/rFIXFc for all age groups, with a corresponding reduction (15‐16%) in actual annualized FIX utilization in switchers (combined adults and children) to rFIXFc, and a smaller non‐significant reduction in actual annualized FVIIII utilization (7%) in children who switched to rFVIIIFc. A significant reduction in the median ABR was only observed in children who switched to rFVIIIFc, but not in adults who switched to rFVIIIFc or rFIXFc. Conclusion: Switching from SHL to EHL products led to a small reduction in factor utilization, while preserving a low ABR in children and adults with haemophilia. Further patient‐reported outcomes data will further elucidate the role of EHL in the haemophilia landscape. [ABSTRACT FROM AUTHOR]

Introduction: Severe haemophilia A (HA) has a major impact on health‐related quality of life (HRQoL). Aim: Assess the impact of emicizumab on HRQoL in persons with severe HA (PwHA) without factor VIII (FVIII) inhibitors in the phase 3 HAVEN 3 and 4 studies. Methods: This pooled analysis examines the HRQoL of PwHA aged ≥ 18 years treated with emicizumab prophylaxis via Haemophilia‐Specific Quality of Life Questionnaire for Adults (Haem‐A‐QoL) and EuroQoL 5‐Dimensions 5‐levels (EQ‐5D‐5L). In particular, changes from baseline in Haem‐A‐QoL 'Physical Health' (PH) domain and 'Total Score' (TS) are evaluated. Results: Among 176 evaluable participants, 96 (55%) had received prior episodic treatment and 80 (45%) prophylaxis; 70% had ≥ 1 target joint and 51% had experienced ≥ 9 bleeds in the previous 24 weeks. Mean Haem‐A‐QoL PH and TS improved after emicizumab initiation. Mean (standard deviation) –12.0 (21.26)‐ and –8.6 (12.57)‐point improvements were observed in PH and TS from baseline to Week 73; Week 73 scores were 27.9 (24.54) and 22.0 (14.38), respectively. Fifty‐four percent of participants reported a clinically meaningful improvement in PH scores (≥ 10 points) by Week 73. Subgroups with poorer HRQoL prior to starting emicizumab (i.e. receiving episodic treatment, ≥ 9 bleeds, target joints) had the greatest improvements in PH scores, and corresponding reductions in missed workdays; change was not detected among those previously taking prophylaxis. No change over time was detected by the EQ‐5D‐5L questionnaire. Conclusions: Emicizumab prophylaxis in PwHA without FVIII inhibitors resulted in persistent and meaningful improvements in Haem‐A‐QoL PH and less work disruption than previous treatment. [ABSTRACT FROM AUTHOR]

Introduction: Emicizumab has been shown to be safe and effective for prevention of bleeds in patients with severe haemophilia A (SHA), both with and without inhibitors. The subcutaneous administration and long half‐life make emicizumab an attractive option for prophylaxis in infants with SHA, however data to inform treatment decisions in this younger age group are almost absent. Aim: The aim of this report is to share real world experience to illustrate how the availability of emicizumab has shifted the prophylaxis paradigm in the management of infants with SHA. Method: We selected four cases from our own cohort of infants with SHA to outline the rationale for emicizumab prophylaxis in a range of scenarios familiar to paediatric haemophilia treaters. Results: In Case 1 emicizumab was commenced at 7 days following initial treatment of neonatal ICH with a FVIII infusion. In Case 2 emicizumab was commenced at 5 weeks due to parental anxiety regarding the potential for ICH during infancy. Case 3 commenced emicizumab at 15 months in lieu of standard primary prophylaxis. Case 4 switched to emicizumab prophylaxis at 14 months after a period of primary prophylaxis with FVIII concentrates to alleviate parental anxiety regarding future inhibitor development. No patient had any bleeding events after commencement of emicizumab (median follow up 12 months), and no drug‐related adverse effects were observed. Conclusion: Despite the paucity of data in infants with SHA the potential role of emicizumab prophylaxis should be discussed with families when clinically relevant, with decisions tailored to individual need. [ABSTRACT FROM AUTHOR]

Introduction: SCT800 is a recombinant human B‐domain‐deleted coagulation factor VIII (BDDrFVIII) developed in China. Aim: To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A. Methods: A phase III, multicentre, prospective, open‐label, single‐arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed. Results: A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01‐3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1–2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment‐related adverse events was 53.4%. Drug‐related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified. Conclusions: SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A. [ABSTRACT FROM AUTHOR]

Introduction: Emicizumab is the first approved non‐factor therapy for haemophilia A. It provides superior prophylactic bleeding control compared to other products in both patients with and patients without inhibitors. However, there is no real‐world data about the monetary consequences of starting emicizumab. Aim: To examine the estimated costs of starting emicizumab in a cohort of real‐world haemophilia A patients with and without inhibitors. Methods: The cost of haemostatic therapy for 6 months before and after initiating emicizumab for participants in a multicentre observational study was calculated based on the type of product and dosing that was used for prophylaxis and treating breakthrough bleeds, the number of treated bleeds and the participant weight. Results: Ninety‐two patients were included, 18 with an active inhibitor. The median age was 8.7 years. The median total cost for all patients decreased from $176,720 to $128,099 (p =.04) after initiating emicizumab, largely because of decrease in the total cost of high‐cost outliers. The cost of prophylaxis and the total cost of bleeds also significantly decreased after starting emicizumab, both for patient with and patients without inhibitors. Conclusions: Starting or switching to prophylaxis with emicizumab results in decreased costs for the treatment of patients with haemophilia A. This real‐world data could inform on payer decisions as well as future cost‐effective analysis. [ABSTRACT FROM AUTHOR]

Objective: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first‐year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership. Methods: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort. We used a multinomial logistic regression to predict the odds of class membership based on the above predictors. We fitted a survival model to assess whether there were differences in the rate of dose escalation across the groups. Results: We identified three distinct classes of trajectory: persistently low, moderately increasing and rapidly increasing joint scores. By multinomial regression, we found that only age at first index joint bleed predicted rapidly increasing joint scores. The rapidly increasing joint score class group moved through dose escalation significantly faster than the other two groups. Conclusions: Using tailored prophylaxis, boys with SHA follow one of three joint health trajectories. By using knowledge of disease trajectories, clinicians may be able to adjust treatment according to a subject's predicted long‐term joint health and institute cost‐effective programmes of prophylaxis targeted at the individual subject level. [ABSTRACT FROM AUTHOR]

Background: The traditional weight‐based dosing regimen can lead to under‐ or overdosage due to the interindividual variability of pharmacokinetic (PK) parameters. PK‐guided prophylaxis can be an optimized therapy choice. Aim: This study aimed to investigate the clinical outcomes of PK‐guided prophylaxis in 46 boys with severe haemophilia A. Methods: Forty‐six boys with severe haemophilia A were enrolled in Beijing Children's Hospital. The PK tests were performed using a five‐point assay. PK parameters were calculated using WinNonlin software. The dosing regimen and bleeding rates recorded during the observation period. The adjustment was based on PK evaluation, bleeding details, doctor's advice and patients' choice. Results: The half‐life time, in vivo recovery and clearance of Kovaltry were 14.34 ± 2.68 h, 1.78 ± 0.29 kg/dl and 3.38 ± 0.94 ml/kg/h, respectively. In 18 patients without any change in the dosing regimen, the trough level was 4.0 ± 2.41 IU/dl and the bleeding rates were similar after PK tests. For patients with a higher trough level after adjustment, higher dose and frequency were observed, as well as a higher trough level. Also, reduced annual bleeding rate (ABR), annual joint bleeding rate and annual spontaneous bleeding rate (ASBR) were found. In five patients with a reduced trough level, lower infusion frequency and weekly coagulation factor VIII (FVIII) consumption were observed, with no statistically significant difference in ABR and ASBR. Conclusion: PK‐guided prophylaxis can help haemophiliac patients improve quality of life by decreasing bleeds with appropriate FVIII consumption and reducing infusion frequency without increments in bleeds, thus optimizing haemophilia treatment. [ABSTRACT FROM AUTHOR]

Introduction: The use of pharmacokinetic assessment for optimal prophylactic dosing of factor concentrates in haemophilia has gained increasing enthusiasm over the last decade. However, blood sampling on several occasions is burdensome and limited sampling using population‐based PK is appealing. Aim: To compare the pharmacokinetics and dosing recommendations for prophylaxis using six‐point single subject versus population‐based method (WAPPS‐Hemo) for simoctocog alfa (Nuwiq®). Methods: Twelve adult patients with severe haemophilia A received a factor VIII (FVIII) dose of ≈50 IU/kg, and the activity was measured pre‐infusion and at 30 min, 6, 9, 24 and 48 h post‐infusion. Half‐life (t1/2), weight‐normalized AUC and time to troughs of 5%, 3% and 1% were calculated. The correlation between the PK algorithms was assessed using intraclass correlations (ICC) and dosing estimations were provided. Results: WAPPS‐Hemo yielded a slightly longer mean t1/2, but the overall correlation between the methods was good (ICC ≥0.79) The time to troughs of 5%, 3% and 1% showed ICCs ≥0.86. For all variables, the most converging limited time point was 6+48 h. Additional time points did not improve the correlation. Despite similar pharmacokinetics, the mean estimated dose for a specific trough level varied from 60% less to 20% more using the population‐based approach. The time to 1% and the corresponding dose was sensitive to the baseline assumption. Conclusion: Our data support the use of population‐based PK for patients on simoctocog alfa prophylaxis but also indicates differences, stressing the importance of the sampling scheme and monitoring actual FVIII levels achieved. [ABSTRACT FROM AUTHOR]

The need to reduce the burden of injections, and improve adherence and clinical outcomes in haemophilia A led to the development of recombinant FVIII products endowed with an extended plasma half‐life (EHL‐rFVIII) in comparison with standard half‐life products (SHL‐rFVIII). Lack of head‐to‐head studies makes difficult to grasp the relative value of each treatment option. We conducted a combined evaluation of the individual pivotal trials in order to assess between‐product differences regarding the reported efficacy results and FVIII consumption. We evaluated 4 EHL‐rFVIII products available to treat patients with haemophilia A without inhibitors and also a SHL‐rFVIII as a comparator. In the frame of these clinical studies, all the EHL‐rFVIII products showed a decrease in the injection burden coupled with good clinical efficacy, even though there were between‐product differences in terms of reduction in injection frequencies. Further, between‐product differences in terms of weekly/yearly consumption of rFVIII expressed in IU/Kg were identified, suggesting a different economic impact for the different EHL‐rFVIII products in the context of comparable clinical efficacy. The present findings based upon the review of pivotal studies done in the frame of a highly selected clinical scenario should be integrated with real‐life data. [ABSTRACT FROM AUTHOR]

Introduction: Primary prophylaxis is the current gold standard in haemophilia care for the prevention of bleeding and ensuing joint damage. Early detection of joint bleeding, whether symptomatic or subclinical, preferably during childhood, helps prevent joint deterioration and subsequent disability. The aim of this study is to evaluate the level of agreement between the Haemophilia Joint Health Score and the Haemophilia Early Arthropathy Detection with Ultrasound tools in children with severe haemophilia on primary and secondary prophylaxis. Materials and Methods: All patients were followed up regularly at our centre. Elbows, knees and ankles were evaluated by physical examination using the Haemophilia Joint Health Score 2.1 (HJHS 2.1), and by ultrasound with HEAD‐US score. Results: A total of 80 children with haemophilia on prophylaxis were included in this study. Mean age was 10.8 years (range 4–18). We evaluated 480 joints, of which 423 (88.1%) were concordant with both tools, whereas 57 (11.9%) were discordant; 377 (78.5%) joints scored 0 on HJHS, 370 (77%) on HEAD‐US and 345 (72%) on both tools. The overall Kappa concordance coefficient was.656. For elbows, knees and ankles the respective values were.783,.522 and.589. For HJHS scores greater than 3, all joints scored ≥1 on HEAD‐US. Conclusion: HJHS and HEAD‐US are used to assess joint health in children with haemophilia on prophylaxis. In this study, the level of agreement between both tools was consistent with literature values only for the elbow joint. [ABSTRACT FROM AUTHOR]

Introduction: In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half‐life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis. Aims: To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real‐world setting. Methods: Data collected retrospectively from electronic diaries and medical records of PWSHB for a two‐year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment. Results: 28 PWSHB (≥18 years) were enrolled, and at switchover 79% were receiving prophylaxis and 21% episodic treatment with SHL rFIX. At 24 months following switchover, all remained on rFIXFc prophylaxis with reduced infusion frequency; median dose per infusion once weekly (55 IU/kg, 20/28), every 10 days (63 IU/kg, 2/28) or every 14 days (98 IU/kg, 6/28). Median annualised bleed rate improved significantly on rFIXFc prophylaxis (2.0 versus 3.3 on SHL FIX) (p = 0.01). Median FIX trough level with once‐weekly infusions was 0.09 IU/ml (0.06–0.14 IU/ml). Management of bleeding episodes was similar with rFIXFc and SHL rFIX; one infusion was sufficient to treat 74% and 77% of bleeds, respectively, with similar total median treatment per bleeding episode. Factor consumption reduced by 28% with rFIXFc prophylaxis (57 IU/kg/week, range 40–86 IU/kg/week) compared with SHL rFIX (79 IU/kg/week, range 44–210 IU/kg/week) (p = 0.002). Conclusion: This study provides important insights into real‐world experience of switching to rFIXFc prophylaxis in an adult population, demonstrating high rates of prophylaxis, with reduced infusion frequency, bleeding and FIX consumption. [ABSTRACT FROM AUTHOR]

Introduction: Although the measurement of physical activity (PA) amongst people with haemophilia (PWH) has become increasingly widespread in recent years, the relationship between PA and bleeding phenotype remains poorly understood. In addition, the influence of various treatment regimens on this relationship has not been defined. Aim: This review aimed to systematically assess the data that are available regarding PA levels amongst PWH, as well as the relationship between PA and bleeding. Methods: A systematic search of the online databases EMBASE, Cochrane, MEDLINE Ovid, CINAHL and Web of Science was conducted by two independent reviewers. Quality assessment was undertaken using the AXIS Critical Appraisal Tool for Cross‐sectional Studies and the STROBE checklist. Results: Of 1902 sources identified overall, 36 articles were included. Low‐to‐moderate transparency of reporting and various sources of bias were identified. PA levels varied amongst heterogeneous samples of PWH. The relationship between PA and bleeds was inconclusive, although there was evidence that improvements in treatment over recent decades have appeared to enable PWH to become more physically active. Conclusion: Based upon the limited available evidence, the relationship between PA and bleeding phenotype in PWH remains unclear. However, with the development of improved prophylaxis treatment regimens in recent years, there is evidence that PA levels have increased, especially amongst people with severe haemophilia. The use of validated outcome measures of PA and more robust reporting of bleeds and treatment regimen are warranted in future research, especially in a rapidly evolving era of new treatments for PWH. [ABSTRACT FROM AUTHOR]

A few case reports suggest that 10 to 30 IU/kg of pdFVII or 20-30 mcg/kg of rFVIIa twice or three times a week is sufficient to prevent major bleeds,9 despite the plasma half-life of rFVIIa being only 2-8 hour.10 It has been suggested that the biological effect of rFVIIa may be longer because of its extravascular redistribution.11 Starting treatment early in life raises the question on how to manage regular administrations of low doses of rFVIIa. Keywords: eptacog alfa; factor VII deficiency; prophylaxis; rFVIIa; sub-dural haematoma EN eptacog alfa factor VII deficiency prophylaxis rFVIIa sub-dural haematoma e487 e490 4 07/21/21 20210701 NES 210701 Inherited factor VII (FVII) deficiency is a rare autosomal recessive bleeding disorder. They were then aliquoted in individual 1 mL syringes, under sterile condition using a laminar flow hood as previously reported.2 Each syringe contained 0.3 mL of rFVIIa, meaning that 6 syringes could be made from only one 2.2 mL vial of rFVIIa (1.2 mg/2.2 mL). However, preparation of rFVIIa syringe aliquots was done in every clinical situation requiring several infusions of rFVIIa (Table 1). [Extracted from the article]