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INTRODUCTION In good risk patients (historic inhibitor peak

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.

Introduction Central venous access devices (CVAD) are used to facilitate intravenous treatment with coagulation factor concentrates (CFCs) in haemophilia A (HA). Guidelines for perioperative CFC replacement therapy are based on single centre experiences, and the length of replacement therapy varies. Aim The aim of this study was to evaluate whether haemostasis coverage under four days is as effective and safe as a longer period of haemostatic coverage. Methods We identified patients with severe HA without inhibitors or major bleeds within one month of the surgery who received their first CVAD. We compared the CFC consumption and bleeds between children with ≤4 and those who received 5-7 perioperative treatment days including the day of surgery. Bleeds were recorded up to 4 days after the end of perioperative haemostatic coverage. Results In total, 144 children met the eligibility criteria and were included in the study cohort: 34 had received haemostatic coverage for ≤4 days, while 110 had received 5-7 days of haemostatic coverage. One bleed related to the surgery occurred in both groups. Conclusion Overall, the bleeding complications were rare. Haemostatic coverage with CFCs under ≤4 days with elective CVAD insertions was as effective as coverage for ≥5 days.

Introduction BAY 94‐9027 (damoctocog alfa pegol; an extended half‐life PEGylated recombinant factor VIII [FVIII]) demonstrated efficacy and safety in previously treated paediatric patients (PTPs) aged

Aim The aim of this study was to investigate whether a disease registry could serve as a suitable alternative to clinical studies to investigate safety of orphan drugs in children. Methods We used individual patient data from previously untreated patients (PUPs) with severe haemophilia A from the factor VIII (rAHF‐PFM)‐clinical study and the PedNet registry. The primary outcome was the patient characteristics at entry and the difference in inhibitor development between the clinical study and the registry‐based study at 50 exposure days. Results Clinical study patients more often had a positive family history of inhibitors (31% vs 10%) and a high‐risk F8 genotype (82% vs 63%). In the clinical study 41/55 (75%) and in the registry‐based study 162/168 (96%) patients reached 50 exposure days. Inhibitors developed in 16 of the 41 patients in the clinical study (39%) vs 44 of the 162 patients in the registry‐based study (27%); seven patients (7%) vs 28 patients (17%) had high‐titre inhibitors. The risk of developing an inhibitor during the first 50 exposure days was similar (HR 1.04; 95% CI 0.56‐1.94), when adjusted for family history of inhibitors, F8 gene mutation and intensive treatment at first exposure. Conclusion In the registry‐based study, patient numbers and completeness of follow‐up were higher. The risk of developing an inhibitor to a single product was comparable. Although the sample size of this study was too small to conclude on differences in high‐ or low‐titre inhibitors, this suggests that a registry could serve as a more suitable source for evaluation of high‐titre inhibitors in the setting of factor VIII deficiency.

Introduction Turoctocog alfa pegol is a glycoPEGylated recombinant factor VIII (FVIII) with an extended half‐life developed for prophylaxis, treatment of bleeds and perioperative management in patients with haemophilia A. Aim Evaluate the efficacy and safety of turoctocog alfa pegol treatment for major and minor surgeries in the pathfinder 3 and 5 phase III trials. Methods Adults/adolescents aged ≥12 years with severe haemophilia A (FVIII 80% during major surgery (pathfinder 3). The primary end point was haemostatic efficacy during surgery; secondary end points were blood loss, haemostatic effect postsurgery, consumption, transfusions, safety and health economics. Children (0‐11 years) undergoing minor surgeries received 20‐75 IU/kg turoctocog alfa pegol at Investigator's discretion (pathfinder 5). Results pathfinder 3 included 35 patients undergoing 49 major surgeries. Haemostasis was successful in 47/49 (95.9%) surgeries; two had moderate haemostatic responses. Median (mean) blood loss during major surgery was 75 (322.6) mL. Four bleeds were reported postsurgery; three were successfully treated with turoctocog alfa pegol (one was not evaluated). On the day of surgery, overall mean (median) dose was 75.5 (74.5) IU/kg and mean (median) number of doses was 1.7 (2.0). Five procedures required 11 transfusions on the day of surgery or days 1‐6. No safety concerns or inhibitors were identified. Forty‐five minor surgeries in 23 children were performed without complications. Conclusion Turoctocog alfa pegol was effective for perioperative haemostatic management of major and minor surgeries in patients across age groups with severe haemophilia A.

Objectives BAY 81‐8973 (Kovaltry®), a full‐length, unmodified, recombinant human factor VIII, provided excellent bleeding control for patients with haemophilia A in the pivotal 1‐year LEOPOLD I trial. The LEOPOLD I extension evaluated long‐term efficacy and safety of BAY 81‐8973 prophylaxis. Methods After completing LEOPOLD I, patients continued receiving 20‒50 IU/kg BAY 81‐8973 two‐ or three‐times weekly in the extension. Outcomes included annualised bleeding rate (ABR) and haemostasis during surgery. Results Fifty‐five patients aged 12‐65 years participated in the extension. Median (range) exposure days during the 2‐year total study period was 309 (115‐355). No patient switched regimens. Median (Q1; Q3) ABR for all bleeds was 2.0 (1.0; 6.1) during the pivotal study, 2.0 (0.0; 5.2) during the extension, and 2.0 (0.5; 5.5) combined. The proportion of joint bleeds affecting target joints decreased (pivotal study: 90.9%, extension: 60.0%). Haemostasis was assessed as excellent/good in all five major surgeries. One serious adverse event (myocardial infarction) occurred in a patient with cardiovascular risk factors. No patients developed inhibitors. Conclusions BAY 81‐8973 prophylaxis efficacy outcomes in the pivotal study were maintained or, in the case of joint protection, improved during the extension, with a safety and tolerability profile consistent with previous experience.

Aim For patients with severe haemophilia A, guidelines recommend prophylactic treatment with FVIII, with dose calculations targeting a predetermined FVIII trough level. However, this pharmacokinetic (PK) approach is suboptimal, with some patients experiencing breakthrough bleeds. We aimed to improve FVIII dosing by incorporating the thrombin generation assay, a global haemostasis assay whose main pharmacodynamic (PD) parameter, endogenous thrombin potential (ETP), predicts spontaneous bleeding risk. Methods We performed post hoc combined PK‐PD modelling using data from 66 adults who received human‐cl rhFVIII (Nuwiq®, Octapharma AG) in a phase IIIb study. Time‐to‐event analyses simulated the probability of spontaneous bleeding for different FVIII exposures and baseline ETPs. Results Ninety‐one spontaneous bleeds occurred in 20/66 patients. The relationship between FVIII:C and ETP was non‐linear, and the sigmoid Emax model adequately described the data. Individual PK‐PD Bayesian estimation significantly improved predictive performance. Simulations showed that the mean spontaneous annual bleeding rate decreased with increasing baseline ETP or dosing: with ETP values of 200, 400 and 600 (nmol/L)·min annual bleeding rates were 2.36, 1.25 and 0.66, respectively, on 40 IU/kg human‐cl rhFVIII every 3 days; and annual bleeding rates were 2.09, 1.10, and 0.60, respectively, on 60 IU/kg every 3 days. Conclusion Prophylactic FVIII dosing is more clinically meaningful when incorporating ETP alongside FVIII level. For the first time, FVIII dosing can be personalized with the aim of eliminating spontaneous breakthrough bleeds.

INTRODUCTION In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs). AIM To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT). METHODS A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. RESULTS The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P

Introduction SHP656 is the first factor VIII (FVIII) product developed using polysialylation (PSA) technology, in which full‐length recombinant (r) FVIII (anti‐haemophilic factor [recombinant]) is conjugated with a 20 kDa PSA polymer. Aim To compare the safety, immunogenicity and pharmacokinetics of SHP656 vs the parent rFVIII (octocog alfa) after single infusions of 25‐75 IU/kg in patients with severe haemophilia A (FVIII activity

INTRODUCTION A dedicated emicizumab assay based on the modified one-stage factor VIII (FVIII) assay (mOSA) is mainly available in haemophilia treatment centres (HTC). A method to estimate emicizumab plasma levels based on a widely available assay would be desirable, especially for emergency situations. AIM A method for emicizumab plasma level approximation (ELA) using a routine FVIII activity measurement with standard one-stage assay (sOSA) was developed and evaluated. METHOD Within this pilot study, 59 samples from patients with severe haemophilia A with (n = 8) and without (n = 8) inhibitors under emicizumab treatment were analysed using sOSA following a manual 1:8 sample pre-test dilution with saline. The sOSA was determined in two different laboratories, using two different analyser platforms each. RESULTS The results demonstrated an excellent correlation of approximated emicizumab plasma levels (ELA) with the emicizumab plasma concentration determined with mOSA (r > .9; p

We investigated longitudinally the behaviour of anti-factor VIII (anti-FVIII) IgG subclasses for 6 months from inhibitor development in 43 patients from the Survey of Inhibitors in Plasma-Products Exposed Toddlers (SIPPET) trial who developed persistent or transient inhibitors. We first analysed 43 patients within 60 days post inhibitor detection. Then, 14 of these 43 patients were studied at five time points over 6 months. Our study showed that during the first 60 days, the risk of inhibitor persistence increased with the concomitant presence of an increasing number of IgG subclasses. Over the 6-month period post inhibitor detection, only the IgG2 subclass could be considered a hallmark of inhibitor persistence.

We describe the case of a patient with severe hemophilia A who underwent major orthopedic surgery managed postoperatively by telemedicine (TM). The case is a splendid example of the implementation of TM and good collaboration between a Comprehensive Hemophilia Treatment Center (CHTC) and a local hospital.

INTRODUCTION Desmopressin is an effective haemostatic agent for patients with non-severe haemophilia A; however, response may differ between patients of similar severity. Responsiveness is classified based on various cut-off values for plasma levels of FVIII post-desmopressin administration. Patients may be classified differently depending on the values chosen. AIM To classify desmopressin response in non-severe haemophilia A patients with respect to current test-response definitions. Also, to characterize relationships between test response and clinical outcome of desmopressin use. METHODS Current desmopressin test-response definitions were obtained from the literature. We adopted peak FVIII level (at 1 hour post-administration) ≥50 IU/dL and

INTRODUCTION For individuals with haemophilia A, prophylaxis with factor VIII (FVIII) is typically directed towards trough activity >1 IU/dL; however, some patients still experience spontaneous bleeding events (sBEs). AIM Aims were to evaluate relationships of endogenous thrombin potential (ETP) and FVIII:C with occurrence of clinical bleeding. METHODS GENA-21 was a prospective, open-label, phase IIIb study investigating the safety and efficacy of Nuwiq® (human-cl rhFVIII) in previously treated adults with severe haemophilia A. The study included a 72-hour pharmacokinetic (PK) evaluation phase and a 6-month personalized prophylaxis phase in which treatment was guided by PK parameters. This subanalysis assessed FVIII:C by one-stage assay and ETP by thrombin generation assay in blood samples. RESULTS Baseline mean ETP was lower in the 7 patients who experienced sBEs during personalized prophylaxis versus 25 who did not (n = 32 with data from PK phase and prophylaxis phase; P = .0002). During personalized prophylaxis (n = 49), only patients with lower median trough ETP experienced sBEs (8/49 patients; ROC AUC = 0.9421; P

HemAcure: Application of combined gene and cell therapy within an implantable therapeutic device for the treatment of severe haemophilia A

WOS: 000442583600048, PubMed ID: 29582525, IntroductionThe pharmacokinetics (PK), efficacy and safety of moroctocog alfa (AF-CC) have been demonstrated in haemophilia A patients aged 6years. AimThese studies aimed to further describe moroctocog alfa (AF-CC) experience in paediatric patients (, PfizerPfizer, Pfizer

Introduction Nuwiq® (human-cl rhFVIII, simoctocog alfa) is a 4th generation recombinant human FVIII, without chemical modification or fusion with any other protein, produced in a human cell line. Aim/methods This study (GENA-13) was an extension of the GENA-03 study in which previously treated children aged 2-12 years with severe haemophilia A received Nuwiq® prophylaxis for ≥6 months. GENA-13 examined long-term tolerability, immunogenicity and efficacy of Nuwiq® prophylaxis in children. Results Of 59 patients enrolled in GENA-03, 49 continued Nuwiq® prophylaxis in GENA-13 for a median (range) of 30.0 (9.5-52.0) months. No patient withdrew due to drug-related adverse events or developed inhibitors. Only 2 of 20 518 infusions were associated with possibly related adverse events (dyspnoea, fever). The estimated annualized bleeding rate (ABR) was 0.67 (95% CI: 0.44, 1.02) for spontaneous and 2.88 (95% CI: 1.86, 4.46) for all bleeds. Younger children (2-5 years) had lower ABRs than children aged 6-12 years. Annualized bleeding rates were reduced in GENA-13 vs GENA-03, especially for spontaneous bleeds in younger children (71% reduction; ABR ratio 0.29 [95% CI: 0.11, 0.74]). Nuwiq® efficacy was rated as excellent/good in the treatment of 83.0% of 305 evaluated breakthrough bleeds. Surgical prophylaxis with Nuwiq® was rated as excellent for all 17 assessed procedures. Conclusion Long-term treatment with Nuwiq® for the prevention of bleeds in children with severe haemophilia A was well tolerated, effective and reduced spontaneous bleeding by up to 70% compared with GENA-03.

AimFor previously untreated patients (PUPs) with severe haemophilia A in Finland for the past 2 decades, the standard practice has been to start early primary prophylaxis. We evaluated the long-term clinical outcomes and costs of treatment with high-dose prophylaxis in PUPs from birth to adolescence, including immune tolerance induction (ITI). MethodsFrom the medical records of all PUPs born between June 1994 and May 2013 in Finland, we retrospectively extracted data on clinical outcomes and healthcare use. Using linear mixed models, we analysed longitudinal clinical outcome data. To analyse skewed cost data, including zero costs, we applied hurdle regression. ResultsAll 62 patients received early regular prophylaxis; totally, they have had treatment for nearly 700 patient-years. The median age of starting home treatment was 1.1years. The mean (SD) annual treatment costs (Europerkg) were 4391Euro (3852). For ages 1-3, ITI comprised over half of the costs; in other groups, prophylactic FVIII treatment dominated. With these high costs, however, clinical outcomes were desirable; median (IQR) ABR was low at 0.19 (0.07-0.46) and so was AJBR at 0.06 (0-0.24). Thirteen (21%) patients developed a clinically significant inhibitor, 10 (16%) with a high titre. All ITIs were successful. The mean costs for ITI were 383448Euro (259085). The expected ITI payback period was 1.81 (95% CI 0.62-12.12) years. ConclusionsEarly high-dose prophylaxis leads to excellent long-term clinical outcomes, and early childhood ITI therapy seems to turn cost-neutral generally already in 2years.

Introduction Immune tolerance induction (ITI) is the gold standard for eradication of factor VIII inhibitors in severe haemophilia A; however, it usually requires treatment for extended periods with associated high burden on patients and healthcare resources. Aim Review outcomes of ITI with recombinant factor VIII Fc fusion protein (rFVIIIFc) in patients with severe haemophilia A and high-titre inhibitors. Methods Multicentre retrospective chart review of severe haemophilia A patients treated with rFVIIIFc for ITI. Results Of 19 patients, 7 were first-time ITI and 12 were rescue ITI. Of 7 first-time patients, 6 had at least 1 high-risk feature for ITI failure. Four of 7 first-time patients were tolerized in a median of 7.8 months. The remaining 3 patients continue on rFVIIIFc ITI. Of 12 rescue patients, 7 initially achieved a negative Bethesda titre (≤0.6) in a median of 3.3 months, 1 had a decrease in Bethesda titre and continues on rFVIIIFc ITI and 4 have not demonstrated a decrease in Bethesda titre. Of these 4, 3 continue on rFVIIIFc ITI and 1 switched to bypass therapy alone. Two initially responsive patients transitioned to other factors due to recurrence. Overall, 16 of 19 patients remain on rFVIIIFc (prophylaxis or ITI). For those still undergoing ITI, longer follow-up is needed to determine final outcomes. No adverse events reported. Conclusions Recombinant factor VIII Fc fusion protein demonstrated rapid time to tolerization in high-risk first-time ITI patients. For rescue ITI, rFVIIIFc showed therapeutic benefit in some patients who previously failed ITI with other products. These findings highlight the need to further evaluate the use of rFVIIIFc for ITI.

Background: Inhibitor development in previously untreated patients (PUPs) with severe haemophilia A is a multifactorial event. It is unknown whether paediatric vaccinations given in close proximity to factor VIII (FVIII) are associated with inhibitor development. Objective: To assess whether paediatric vaccinations in close proximity to FVIII within the first 75 exposure days (EDs) are associated with inhibitor development in PUPs with severe haemophilia A. Methods: We included 375 PUPs with severe haemophilia A (

Introduction Haemophilia A patients are at a high risk of excess bleeding during surgeries. The aim of haemostatic therapy during the perioperative period is to normalize FVIII level perioperatively and postoperatively to maintain normal haemostasis until wound healing is complete. Aims/Methods To examine the efficacy of Nuwiq® (simoctocog alfa, human-cl rhFVIII), a 4th generation recombinant FVIII produced in a human cell line, for surgical prophylaxis in patients with severe haemophilia A. This analysis assessed the efficacy of Nuwiq® during surgical procedures and in the postoperative period in seven clinical studies of previously treated patients (PTPs) with severe haemophilia A. Results Thirty-six patients, aged 3-55 years, received surgical prophylaxis with Nuwiq® for 60 surgeries (28 major and 32 minor). Efficacy was evaluated for 52 surgeries (25 major and 27 minor). The success rate of Nuwiq® treatment was 98.1% (51 of 52 evaluated surgeries); haemostatic efficacy was assessed as “excellent” or “good” in all but one major surgery (assessed as “moderate”). The number of infusions ranged from 1 to 19 for minor surgeries and from 3 to 76 for major surgeries. The median (range) daily doses were 42.0 (28.2-100.9) IU kg−1 for minor surgeries and 69.3 (43.3-135.6) IU kg−1 for major surgeries. There were no serious treatment-related adverse events, and none of the patients developed FVIII inhibitors. Conclusions The results of this pooled analysis show that Nuwiq® was efficacious in maintaining haemostasis during and after major and minor surgical procedures in PTPs with severe haemophilia A.

Introduction Adults with severe haemophilia A (SHA) may experience breakthrough bleeds despite standard weight-based FVIII prophylaxis three times weekly. Individualized prophylaxis has evolved to optimize patient outcomes. Aims This study aimed to evaluate the impact of a standardized approach to individualized prophylaxis on annualized bleeding rates (ABR), factor utilization, physical activity and quality of life in adults with SHA. Methods In this prospective cohort study, patients with baseline FVIII:C 3 on weight-based prophylaxis received a standardized approach to individualized prophylaxis. Changes in ABR, annualized FVIII consumption and adherence from the 12-month prestudy and 12-month intervention period were compared. Changes in Haemo-QoL-A total score, Physical Functioning (PF) subscale and physical activity level measured by accelerometry were also examined. Results Eighteen patients participated (median age 26 years). Individualized prophylaxis decreased total bleeds in the population by 69% and traumatic bleeds by 73%. The median ABR decreased from 7.5 to 2 (P

Background Persons with severe haemophilia require lifelong replacement therapy, prophylaxis, to prevent bleeding. Data describing long-term outcomes of prophylactic treatment are scarce. The aim of this study was to investigate joint surgery and survival among persons with severe haemophilia with special attention to access to prophylaxis in the early years of life. Methods Eligible participants had severe haemophilia A or B and were treated at the Malmo centre from the 1960s onward. Time from birth until joint surgery was analysed for participants negative for factor inhibitor and alive in 2000. We compared survival among the entire cohort with severe haemophilia treated at the Malmo centre with the general male population of Sweden and a sample of persons with severe haemophilia from the United Kingdom (UK). Results Overall, 167 participants were included, 106 (63.5%) of whom had complete data on joint surgery. Among those born before 1970, 1970-1979 and ≥1980 approximately 37%, 21% and 0% had their first joint surgery by age 30, respectively. There were no second joint surgeries reported in cohorts born ≥1970. Persons with severe haemophilia and negative for HIV treated in Malmo have attained approximately similar survival to that of the general male population in Sweden and live slightly longer than persons with severe haemophilia from the UK. Discussion and conclusion Prophylaxis in Sweden, although costly, has markedly improved survival and joint outcomes for persons with severe haemophilia. This study highlights the importance of early start of replacement therapy to prevent or postpone serious joint damage.

Introduction Nuwiq® (human-cl rhFVIII) is a 4th generation recombinant human FVIII, without chemical modification or protein fusion, produced in a human cell-line. Aims/Methods This study (NuPreviq) was a prospective, open-label, multicentre, phase IIIb study of the efficacy and safety of personalized prophylaxis with Nuwiq® in 66 previously treated adults with severe haemophilia A. NuPreviq had three phases: (i) a 72-h pharmacokinetic (PK) phase; (ii) a 1–3 month standard prophylaxis phase; and (iii) a 6-month personalized prophylaxis phase. The personalized prophylaxis regimen was based on individual PK modelling for each patient according to whether their PK profile most closely fitted a two- or one-compartment model (NuPreviq approach). In cases of uncertainty, a noncompartment model was applied. Results The median dosing interval during personalized prophylaxis was 3.5 days, with 57% of patients on ≤2 weekly dosing. Mean annualized bleeding rates during personalized prophylaxis were 1.45 (median [interquartile range, IQR]: 0 [0, 1.9]) for all bleeds, 0.79 (median [IQR]: 0 [0, 0]) for spontaneous bleeds, and 0.91 (median [IQR]: 0 [0, 0]) for joint bleeds. During personalized prophylaxis, 83.1% of patients were spontaneous bleed-free. Compared with standard prophylaxis, median weekly prophylaxis dose was reduced by 7.2% from 100.0 to 92.8 IU kg−1 during the last 2 months of personalized prophylaxis. There were no FVIII inhibitors or treatment-related serious or severe adverse events. Conclusion PK-guided personalized prophylaxis with Nuwiq® provided bleeding protection and enabled the dosing interval to be extended to twice weekly or less in many patients and an overall dose reduction.

INTRODUCTION Treatment for boys with haemophilia in China is rapidly improving; however, comprehensive outcomes have not been examined prospectively. AIM The aim of this study was to evaluate the effect of short-term full-dose prophylaxis compared to on-demand treatment, on the Health-Related Quality of Life (HR-QoL) of boys with severe haemophilia A (HA) in China. METHODS Boys with severe HA (FVIII

© 2019 John Wiley & Sons Ltd Introduction: The research was conducted at a UK teaching hospital and Haemophilia Comprehensive Care Centre (CCC) as part of a research programme investigating physiotherapy for acute bleed management. Aim: The aim of the study was to understand the perspectives of people with haemophilia (PWH) on validated outcome measures (OM) and whether these measures capture changes relevant to them whilst recovering from an acute bleed episode. Methods: Any person with haemophilia registered to the CCC who reported an acute bleed within the past 2years was invited to participate. Semi-structured interviews or workshops (activity-focused discussions with small groups) were conducted with PWH who had received physiotherapy treatment in the previous two years. These were used to explore opinions of PWH of commonly used outcome measures. Results: Eight male PWH participated, mean age 61years, ranging between 39 and 71. Seven participants had severe haemophilia A and 1 had von Willebrands. Participants described numerical rating scales of pain as abstract and expressed a preference for verbal or visual descriptors. In relation to function, the men generally found haemophilia-specific OM to be more relevant. The EuroQol 5-Dimension 5-Level (EQ5D-5L) and Haemophilia and Exercise Project Test Questionnaire (HEP-Test-Q) were considered as good measures due to brevity and ability to capture relevant changes promptly. Conclusion: Participants in this study reported a preference for short OMs that allow them to reference their ability during the acute bleed episode in comparison with their normal function.

INTRODUCTION Prophylaxis has commonly become standard treatment for severe haemophilia patients. The World Federation of Hemophilia (WFH) recommends low-dose prophylaxis in countries with resource constraints. OBJECTIVE To determine efficacy and safety of low-dose factor VIII (FVIII) tertiary prophylaxis compared to on-demand treatment in severe haemophilia A children in Indonesia. METHODS Eligible patients were randomly assigned to prophylaxis and on-demand groups. Patients in the prophylaxis group received infusion of FVIII 10 IU/kg body weight, two times per week. Primary outcomes were the numbers of joint bleeding and total bleeding episodes; secondary outcomes were evidence of FVIII inhibitor, Hemophilia Joint Health Score (HJHS) and Hemophilia Early Arthropathy Detection Ultrasound (HEAD-US) score. Patients were monitored for 12 months. RESULTS Fifty patients, all with tertiary prophylaxis, 4-18 years of age, were randomized into prophylaxis (n = 25) and on-demand (n = 25) groups. The mean follow-up time was 12.8 ± 0.86 vs 12.3 ± 0.54 months, respectively. Numbers of total and joint bleeding episodes were significantly lower in the prophylaxis group (P

Curry, Nicola/0000-0002-3849-0688; Escobar, Miguel/0000-0002-2944-0240 WOS: 000470929100022 PubMed: 30817066 Introduction Turoctocog alfa pegol (N8-GP) is a site-specific, 40 kDa glycoPEGylated recombinant factor VIII (FVIII) product with an extended half-life. The comprehensive main phase of the pivotal pathfinder 2 trial showed N8-GP dosed every 4 days (Q4D) provided favourable safety and efficacy for preventing bleeds in 175 patients with haemophilia A. Aim and methods We investigated the safety and efficacy of N8-GP prophylaxis when administered weekly (Q7D) for 24 weeks to patients with low bleeding rates in the pathfinder 2 extension trial. Patients (>= 12 years) with 50% of patients experienced no bleeds. Median ABR for overall, joint, spontaneous, traumatic and muscle was 0.00 for both cohorts. Overall estimated success rate for treating bleeding episodes was 87.5%; 94.7% of bleeds were controlled with

Introduction Primary factor VIII (FVIII) prophylaxis is the optimal treatment in children with severe haemophilia A. They are expected to benefit from extended half-life (T1/2) FVIII coverage by reduced infusion frequency while maintaining haemostatic efficacy. Aims To determine immunogenicity, pharmacokinetics (PK), efficacy, safety and quality of life of prophylaxis with a polyethylene glycol (peg)-ylated FVIII (BAX 855) based on full-length recombinant FVIII (ADVATE) in paediatric previously treated patients (PTPs) with severe haemophilia A. Methods PTPs

Introduction Standard prophylaxis has been shown to be an effective treatment for severe haemophilia A. According to pharmacokinetic principles, daily factor infusions of smaller doses can maintain similar trough factor VIII (FVIII) levels, and perhaps the same protection as standard prophylaxis. Aim This multicentre study examined the feasibility of daily prophylaxis for youth and young adults with severe haemophilia A in Montreal and Toronto. Methods Bleeding rates, joint status, quality of life and physical activity were monitored for 14 patients during this study. At baseline, subjects continued their regular treatment regimen and switched to daily prophylaxis after 4 months; nine had begun daily prophylaxis before enrolment. Additional visits occurred at 8 and 12 months which included a physical examination, inhibitor testing, HJHS and FISH assessments, the CHO-KLAT/Haemo-QoL-A and PDPAR. Treatment satisfaction was assessed using the Treatment Satisfaction Questionnaire for Medication ver.II and perceived difficulty questions at the end of study. Results and conclusions There were no significant changes in quality of life except for concerns with the demanding daily infusion schedule. The number of bleeds did not statistically differ from the initial 4 months of the study to the last 8 months. Monthly bleeding rates from the year prior to the study and during the intervention phase were not statistically different. It was also found that daily prophylaxis used 24% less FVIII compared to standard prophylaxis. Taking all of this into account, we have found that providing daily prophylaxis is feasible and that it is feasible to prospectively study daily prophylaxis in youth and young adults.