43 results on '"Clinical Haemophilia"'
Search Results
2. Assessing the test–retest reliability and smallest detectable change of the Haemophilia Activities List
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Merel A. Timmer, Krista Fischer, Janjaap van der Net, Isolde A R Kuijlaars, and Madelon van Emst
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Adult ,medicine.medical_specialty ,Intraclass correlation ,Haemophilia A ,haemophilia ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Surveys and Questionnaires ,Medicine ,participation ,Humans ,Clinical Haemophilia ,Genetics (clinical) ,Reliability (statistics) ,activities ,reliability ,business.industry ,patient‐reported outcome ,questionnaire ,Infant, Newborn ,Reproducibility of Results ,Hematology ,General Medicine ,Original Articles ,medicine.disease ,Test (assessment) ,Physical therapy ,Patient-reported outcome ,Original Article ,Self Report ,business ,030215 immunology - Abstract
Introduction The Haemophilia Activities List (HAL) is a preferred instrument to measure self-reported limitations in activities in persons with haemophilia (PWH). Information on reliability and interpretability of HAL scores is lacking. Aim To examine the test-retest reliability and smallest detectable change (SDC) of the HAL in adult PWH. Methods Fifty adult (≥18 years) persons with mild to severe haemophilia completed the HAL (42 items, 7 domains, optimum 100) at baseline (T0) and 3-4 weeks later (T1). The intraclass correlation coefficient (ICC) and SDC were calculated for sum and component scores. Results Fifty persons with haemophilia were included (median age 49 years; 92% haemophilia A; 70% severe haemophilia). The median (interquartile ranges) HAL sum score was 77 (62 to 99) at T0 and 81 (64 to 98) at T1. Reliability was good with ICCs for sum and component scores >0.9. The SDC for the sum score was 10.2, for the upper extremity component score 9.2, for the basic lower extremity component score 16.7 and for the complex lower extremity component score 13.4. Conclusion The HAL has a good reliability for the sum and component scores. Score changes of the normalized sum HAL score greater than the SDC 10.2 indicate that the change was not a result of measurement error.
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- 2020
3. Challenges and key lessons from the design and implementation of an international haemophilia registry supported by a pharmaceutical company
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Charles R. M. Hay, Elena Santagostino, Víctor Jiménez-Yuste, Mark W. Skinner, Alfonso Iorio, Sylvia von Mackensen, Midori Shima, Craig M. Kessler, Johannes Oldenburg, Michael Makris, and Krista Fischer
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Male ,medicine.medical_specialty ,clinical outcome ,haemophilia ,registry ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,03 medical and health sciences ,study design ,0302 clinical medicine ,Pharmacovigilance ,Humans ,Medicine ,Registries ,Closure (psychology) ,Clinical Haemophilia ,Genetics (clinical) ,Data collection ,business.industry ,patient‐reported outcome ,Original Articles ,Hematology ,General Medicine ,medicine.disease ,Clinical trial ,Patient recruitment ,Pharmaceutical Preparations ,Family medicine ,Original Article ,Female ,Patient-reported outcome ,multinational ,business ,030215 immunology ,Cohort study - Abstract
Introduction Real‐world data are lacking regarding the relationship between prospectively collected patient‐reported outcomes (PROs), clinical outcomes and treatment in people with haemophilia (PWH). The Expanding Communications on Hemophilia A Outcomes (ECHO) registry was designed to address this data gap, but a range of difficulties led to early study closure. Aim To describe the challenges faced and lessons learned from implementing a multinational haemophilia registry. Methods The Expanding Communications on Hemophilia A Outcomes was planned as a five‐year observational cohort study to collect data from 2000 patients in nine countries. Based on direct observations, feedback from patients enrolled in ECHO, challenges of the study design and input from study‐sponsor representatives, the ECHO Steering Committee systematically identified the challenges faced and developed recommendations for overcoming or avoiding them in future studies. Results The study closed after two years because few countries were activated and patient recruitment was low. This was related to multiple challenges including delayed implementation, stringent pharmacovigilance requirements, objections of investigators and patients to the burden of multiple PROs, data collection issues, lack of resources at study sites, little engagement of patients and competing clinical trials, which further limited recruitment. At study closure, 269 patients had been enrolled in four of nine participating countries. Conclusions Researchers planning studies similar to ECHO may want to consider the barriers identified in this global registry of PWH and suggestions to mitigate these limitations, such as greater patient involvement in design and analysis, clearer assessment and understanding of local infrastructure and potential changes to the administration of the study.
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- 2020
4. Health‐related quality of life and caregiver burden of emicizumab in children with haemophilia A and factor VIII inhibitors—Results from the HAVEN 2 study
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Midori Shima, Guy Young, Robert F. Sidonio, Johannes Oldenburg, Johnny Mahlangu, Marianne Uguen, Maria Elisa Mancuso, Tiffany Chang, Peter Trask, and Sylvia von Mackensen
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Male ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Haemophilia A ,haemophilia ,Day care ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Hemophilia A ,Haemophilia ,03 medical and health sciences ,0302 clinical medicine ,children ,Quality of life ,Antibodies, Bispecific ,inhibitors ,medicine ,Humans ,Patient Reported Outcome Measures ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Emicizumab ,Health related quality of life ,caregiver burden ,Factor VIII ,emicizumab ,health‐related quality of life ,business.industry ,Infant ,Physical health ,Original Articles ,Hematology ,General Medicine ,Caregiver burden ,medicine.disease ,Child, Preschool ,Quality of Life ,Female ,Original Article ,business ,030215 immunology - Abstract
Introduction Persons with haemophilia A (PwHA) with factor (F)VIII inhibitors, including children, have impaired health‐related quality of life (HRQoL). The HAVEN 2 study (NCT027955767) of paediatric PwHA with FVIII inhibitors demonstrated that subcutaneous emicizumab prophylaxis resulted in low annualizedbleed rates. Aim We assessed the impact of emicizumab prophylaxis on the HRQoL of children and their caregivers participating in HAVEN 2. Methods Children aged 8‐11 years self‐reported HRQoL using the Haemophilia‐Specific Quality of Life Assessment Instrument for Children and Adolescents Short Form (Haemo‐QoL SF II). Caregivers of children aged 0‐11 years completed the Adapted Inhibitor‐Specific Quality of Life Assessment with Aspects of Caregiver Burden. All scores were transformed to a 0‐100 scale, where lower scores reflect a better HRQoL. The number of missed days from school/day care and hospitalizations was also recorded. Results In HAVEN 2 (n = 88), the median age was 6.5 years (range: 1‐15 years); 85 participants were aged
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- 2020
5. Real‐world data demonstrate improved bleed control and extended dosing intervals for patients with haemophilia B after switching to recombinant factor IX Fc fusion protein (rFIXFc) for up to 5 years
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Christopher Barnowski, Miguel A. Escobar, Amy D. Shapiro, Doris Quon, Ateefa Chaudhury, Nisha Jain, Michael Wang, Elisa Tsao, and Jing Feng
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Recombinant Fusion Proteins ,Hemorrhage ,haemophilia B ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia B ,Factor IX ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Haemophilia B ,Dosing ,Clinical Haemophilia ,Child ,Genetics (clinical) ,extended half‐life factor ,Aged ,Retrospective Studies ,business.industry ,prolonged factor IX activity ,Hematology ,General Medicine ,Original Articles ,Bleed ,Middle Aged ,medicine.disease ,Immunoglobulin Fc Fragments ,Clinical trial ,Fc fusion ,rFIXFc ,Child, Preschool ,Original Article ,factor IX switching ,Female ,business ,Real world data ,030215 immunology ,Recombinant factor IX - Abstract
Introduction In clinical trials, recombinant factor IX fusion protein (rFIXFc) has demonstrated safety, efficacy and prolonged activity with extended dosing intervals for treatment of haemophilia B. Aim To assess the real-world clinical utility of rFIXFc in a variable patient population and routine clinical practice. Methods A multicentre, retrospective chart review was conducted of patients with haemophilia B who had received rFIXFc prophylaxis or on-demand treatment for ≥6 months across six sites in the United States. Results Sixty-four eligible patients were identified who had a median (range) duration on rFIXFc of 2.7 (0.5-5.0) years. Of 32 patients on rFIXFc prophylaxis who switched from prophylaxis with another factor treatment (ie pre-rFIXFc) and had a known pre-rFIXFc dosing interval, the initial dosing interval was lengthened for 26 (81%) patients and maintained for the remaining 6 (19%) patients. Most (n = 48 [91%]) patients who received rFIXFc prophylaxis from the beginning to the end of the chart review period (n = 53) maintained or lengthened the dosing interval from first through last dose of rFIXFc. For patients receiving rFIXFc prophylaxis, there was an approximate 50% reduction in weekly factor consumption compared with pre-rFIXFc prophylaxis. Overall annualized bleed rates, annualized spontaneous bleed rates and annualized joint bleed rates decreased after switching to rFIXFc prophylaxis (n = 24 with bleed data). Compliance to recommended treatment improved or remained stable in most patients with available data (30/31). Conclusion Recombinant factor IX fusion protein prophylaxis improved bleed control, reduced overall consumption, reduced frequency of infusion and improved compliance for patients with haemophilia B in a real-world setting.
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- 2020
6. Inhibitor development in previously untreated patients with severe haemophilia: A comparison of included patients and outcomes between a clinical study and a registry‐based study
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H. Marijke van den Berg, Peter G. M. Mol, Arno W. Hoes, Carla J. Jonker, Katrien Oude Rengerink, and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
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Male ,previously untreated patients ,medicine.medical_specialty ,PREDICTION ,Haemophilia A ,haemophilia A ,registry ,030204 cardiovascular system & hematology ,Gene mutation ,Hemophilia A ,Orphan drug ,03 medical and health sciences ,0302 clinical medicine ,Disease registry ,Risk Factors ,FACTOR-VIII INHIBITORS ,Internal medicine ,SUPPORT ,Genotype ,medicine ,Humans ,Registries ,Family history ,Child ,Clinical Haemophilia ,Genetics (clinical) ,business.industry ,Original Articles ,Hematology ,General Medicine ,medicine.disease ,inhibitor development ,PRODUCTS ,Treatment Outcome ,TRIALS ,factor VIII ,Sample size determination ,Child, Preschool ,Female ,Original Article ,Severe haemophilia A ,RARE DISEASES ,business ,030215 immunology - Abstract
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.
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- 2020
7. Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials
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Kingsley Hampton, Steven R. Lentz, Chunduo Shen, Elena Santagostino, Karina Meijer, Anne T. Neff, Jameela Sathar, Alberto Tosetto, Andrea Landorph, László Nemes, Pratima Chowdary, and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
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Male ,PHARMACOKINETICS ,SURGERY ,030204 cardiovascular system & hematology ,FACTORVIII ,0302 clinical medicine ,hemic and lymphatic diseases ,Clinical endpoint ,Medicine ,extended half-life ,CLINICAL-EVALUATION ,Genetics (clinical) ,Not evaluated ,extended half‐life ,FACTOR-VIII ,Hematology ,General Medicine ,Middle Aged ,Recombinant Proteins ,REPLACEMENT ,factor VIII ,SAFETY ,Original Article ,Female ,Severe haemophilia A ,PLASMA/ALBUMIN-FREE METHOD ,Adult ,medicine.medical_specialty ,Adolescent ,Haemophilia A ,turoctocog alfa pegol ,haemophilia A ,Hemophilia A ,Haemophilia ,GLYCOPEGYLATED RECOMBINANT FVIII ,Young Adult ,03 medical and health sciences ,Humans ,In patient ,Clinical Haemophilia ,Aged ,business.industry ,Original Articles ,Perioperative ,Turoctocog alfa ,EFFICACY ,medicine.disease ,Surgery ,haemostasis ,Minor Surgical Procedures ,business ,030215 immunology - Abstract
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.
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- 2020
8. Hemostatic prophylaxis and colonoscopy outcomes for patients with bleeding disorders: A retrospective cohort study and review of the literature
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C. Christopher Hook, Rajiv K. Pruthi, Amy Eckerman, Sarah M. Azer, William L. Nichols, Aneel A. Ashrani, Vilmarie Rodriguez, and Ariela L. Marshall
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Adult ,Male ,medicine.medical_specialty ,Psychological intervention ,haemophilia ,Colonoscopy ,Hemorrhage ,030204 cardiovascular system & hematology ,Haemophilia ,Hemostatics ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Von Willebrand disease ,Humans ,Clinical Haemophilia ,Genetics (clinical) ,Aged ,Retrospective Studies ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Exact test ,Treatment Outcome ,Hemostasis ,Cohort ,Original Article ,Female ,prophylaxis ,von Willebrand disease ,business ,030215 immunology - Abstract
Introduction Hemostatic prophylaxis (HP) is recommended for patients with bleeding disorders (PWBD) before invasive procedures. However, evidence‐based guidelines are needed to determine optimal HP strategies. Aim To determine outcomes of HP for PWBD undergoing colonoscopy. Methods We undertook a retrospective cohort study of HP and outcomes of colonoscopy procedures performed between 9 November 1993 and 13 February 2018 for PWBD who received care in the Mayo Clinic Comprehensive Hemophilia Treatment Center. Results During the study period, 73 PWBD (58 with milder phenotypes: haemophilia, von Willebrand disease [subtypes 1 and 2; II, VII and XI deficiency]) underwent 141 procedures. Preprocedural HP was given to 61%, and interventions were performed in 47%. Of the 39% without preprocedural HP, postprocedural HP was given for 11%. One major (0.7%; 6 days postprocedure despite HP) and 10 minor (7%) bleeding complications occurred, which tended to be in patients with severe disease and/or after excision of larger polyps. There was no significant difference in the rate of bleeding complications with or without preprocedural HP (8.1% vs 5.5%, respectively; P = .74, Fisher's exact test). Conclusion The low bleeding rates in our cohort suggest that preprocedure HP may be withheld for patients with mild bleeding disorders who undergo colonoscopy with a low likelihood of requiring an intervention or who require only low‐risk intervention. This strategy may be best used in experienced centres, provided optimal local hemostasis measures are undertaken and postprocedural HP is rapidly available if high‐risk intervention is required. Further studies are needed to determine optimal evidence‐based HP strategies for PWBD undergoing colonoscopy.
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- 2020
9. Recombinant factor VIII Fc fusion protein for the treatment of severe haemophilia A: Final results from the ASPIRE extension study
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Bent Winding, Keiji Nogami, Guy Young, Chris Barnes, Huixing Yuan, Johannes Oldenburg, Elena Santagostino, Liane Khoo, Beatrice Nolan, Barbara A. Konkle, Joachim Fruebis, K. John Pasi, Ingrid Pabinger, Dan Rudin, and Johnny Mahlangu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Recombinant Fusion Proteins ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Recombinant factor viii ,bleed rate ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Clinical Haemophilia ,Child ,Genetics (clinical) ,rFVIIIFc ,Aged ,extended half‐life ,Factor VIII ,business.industry ,Hematology ,General Medicine ,Original Articles ,Bleed ,Middle Aged ,medicine.disease ,Confidence interval ,Immunoglobulin Fc Fragments ,Regimen ,Fc fusion ,Treatment Outcome ,individualized prophylaxis ,Child, Preschool ,Severe haemophilia A ,Original Article ,Female ,business ,perioperative haemostasis ,030215 immunology - Abstract
Introduction The efficacy and safety of recombinant factor VIII Fc fusion protein (rFVIIIFc) as an extended half‐life treatment for severe haemophilia A were demonstrated in the Phase 3 A‐LONG and Kids A‐LONG studies. Eligible subjects who completed A‐LONG and Kids A‐LONG could enrol in ASPIRE (NCT01454739), an open‐label extension study. Aim To report the long‐term safety and efficacy of rFVIIIFc in subjects with severe haemophilia A who enrolled in ASPIRE. Methods Previously treated subjects received one or more of the following regimens: individualized prophylaxis (IP), weekly prophylaxis, modified prophylaxis or episodic treatment. Subjects could switch treatment regimen at any time. The primary endpoint was inhibitor development. Results A total of 150 subjects from A‐LONG and 61 subjects from Kids A‐LONG enrolled in ASPIRE. Most subjects received the IP regimen (A‐LONG: n = 110; Kids A‐LONG: n = 59). Median (range) treatment duration in ASPIRE for subjects from A‐LONG and Kids A‐LONG was 3.9 (0.1‐5.3) years and 3.2 (0.3‐3.9) years, respectively. No inhibitors were observed (0 per 1000 subject‐years; 95% confidence interval, 0‐5.2) and the overall rFVIIIFc safety profile was consistent with prior studies. For subjects on the IP regimen, annualized bleed rates (ABR) remained low (median overall ABR for adults and adolescents was
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- 2020
10. A new paradigm for personalized prophylaxis for patients with severe haemophilia A
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Edouard Ollier, Anne Lienhart, Xavier Delavenne, and Yesim Dargaud
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Adult ,Male ,Adolescent ,business.operation ,Post hoc ,Haemophilia A ,haemophilia A ,030204 cardiovascular system & hematology ,Hemophilia A ,Octapharma ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,thrombin generation assay ,Pharmacokinetics ,hemic and lymphatic diseases ,Humans ,Medicine ,Dosing ,Clinical Haemophilia ,Genetics (clinical) ,Aged ,business.industry ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,bleeding ,medicine.disease ,Treatment Outcome ,factor VIII ,Anesthesia ,Pharmacodynamics ,Trough level ,Female ,Original Article ,Severe haemophilia A ,prophylaxis ,business ,pharmacokinetics ,030215 immunology - Abstract
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.
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- 2020
11. Diagnostic work up of patients with increased bleeding tendency
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Clint van Duren, Saskia E M Schols, Tim J Schuijt, Joline L Saes, Suzanne A M Zegers, Y. Smit, and Waander L. van Heerde
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platelet function disorder ,Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Hemorrhage ,coagulation factors ,030204 cardiovascular system & hematology ,haemostasis disorders ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Fibrinolysis ,Humans ,Medicine ,In patient ,Clinical Haemophilia ,Genetics (clinical) ,Retrospective Studies ,Adult patients ,business.industry ,Original Articles ,Hematology ,General Medicine ,Work-up ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,Laboratory screening ,Von Willebrand factor.activity ,Original Article ,fibrinolysis ,Female ,business ,030215 immunology - Abstract
Contains fulltext : 218269.pdf (Publisher’s version ) (Open Access) INTRODUCTION: The diagnostic trajectory of patients with increased bleeding tendency can be very costly and time-consuming. In addition, previous studies have shown that half of these patients remain without final diagnosis despite all efforts. AIM: This study aimed to improve insight into the current diagnostic process of these patients. METHODS: A total of 117 adult patients, referred to an academic hospital because of being suspected to have an increased bleeding tendency, were included. Different parameters were compared between patients receiving final diagnosis, patients without final diagnosis but a high Tosetto bleeding assessment tool (BAT) score (classified as bleeding of unknown cause, or BUC) and a control group consisting of patients without final diagnosis and a low BAT score. RESULTS: The BAT score was significantly higher in patients in the BUC group as compared to patients reaching final diagnosis (8.1 vs 4.9). Interestingly, the two subcategories most prevalently increased were surgery and post-partum haemorrhage-associated bleeding (surgery: 2.1 vs 1.1; post-partum haemorrhage: 0.7 vs 0.0). Laboratory screening results were more often abnormal in patients reaching final diagnosis compared to patients remaining without diagnosis and a high BAT score (n = 32 (78%) vs n = 14 (46%), 95% CI 1.5-12), especially concerning the PFA (=27 (66%) vs n = 10 (33%), 95% CI 1.4-10) and von Willebrand factor activity levels (n = 11 (27%) vs n = 1 (3%), 95% CI 1.3-91). CONCLUSION: Isolated high bleeding score on surgical or post-partum bleeding correlates with a lower chance of receiving final diagnosis. Withholding extensive haemostatic testing should be considered. Better screening and confirmative haemostatic assays are still needed.
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- 2019
12. Safety and efficacy of turoctocog alfa in the prevention and treatment of bleeds in previously untreated paediatric patients with severe haemophilia A: Results from the guardian 4 multinational clinical trial
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Kaan Kavakli, Meriem Belhani, Kirsten Reichwald, Lars Korsholm, Runhui Wu, Hassan M. Yaish, Irina Matytsina, Víctor Jiménez-Yuste, Claire S. Philipp, Tadashi Matsushita, UAM. Departamento de Medicina, Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ), and Ege Üniversitesi
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Male ,medicine.medical_specialty ,previously untreated patients ,Medicina ,Haemophilia A ,Population ,030204 cardiovascular system & hematology ,immunogenicity ,Bethesda unit ,Haemophilia ,Hemophilia A ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,education ,Clinical Haemophilia ,Child ,Genetics (clinical) ,Paediatric patients ,education.field_of_study ,recombinant factor VIII ,Factor VIII ,business.industry ,Infant, Newborn ,Infant ,Hematology ,General Medicine ,Turoctocog alfa ,Original Articles ,medicine.disease ,Clinical trial ,Treatment Outcome ,Mutation ,Original Article ,turoctocog alfa ,business ,030215 immunology ,annualized bleeding rate - Abstract
Introduction Turoctocog alfa is a recombinant, B domain-truncated factor VIII (FVIII) approved for patients with haemophilia A. Aim To evaluate the safety and efficacy of turoctocog alfa in previously untreated patients (PUPs) with severe haemophilia A. Methods Guardian 4 was a multicentre, multinational, non-randomized, open-label phase 3 trial comprising a main and extension phase. the former concluded once >= 50 patients had received treatment for >= 50 exposure days (EDs) or developed inhibitors. Patients received turoctocog alfa intravenously for prevention and treatment of bleeds. the primary endpoint was the incidence rate of FVIII inhibitors (>= 0.6 Bethesda Units) reported during the first 50 EDs. Results of the 58 patients who completed the main phase, 25 (43.1%) patients developed inhibitors (detected within 6-24 [mean: 14.2] EDs from treatment start). High-risk mutations were identified in 60% of patients who developed inhibitors in the main phase and were a significant predictor of inhibitor development (P = .003). of the 21 patients who started immune tolerance induction therapy, 85.7% completed treatment with a negative inhibitor test (note that data on the last 3 patients completing ITI are based on information collated from sites prior to the final database lock). Haemostatic response (including missing values as failure) was rated as 'excellent' or 'good' for 86.1% of bleeds occurring during prophylaxis. the estimated mean annualized bleeding rate for patients on prophylaxis was 4.26 bleeds/patient/year (95% CI: 3.34 - 5.44). Conclusions Turoctocog alfa was effective at preventing and stopping bleeds and was well tolerated. Inhibitor development was within the expected range for this PUP population., Novo Nordisk A/SNovo Nordisk Funding Source: Medline
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- 2019
13. SHP656, a polysialylated recombinant factor VIII (PSA‐rFVIII): First‐in‐human study evaluating safety, tolerability and pharmacokinetics in patients with severe haemophilia A
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Andreas Tiede, Pratima Chowdary, Margarita Timofeeva, Geoffrey Allen, Kathleen Kӧck, Martin J. Wolfsegger, Alexander Bauer, Hongyu Jeanne Jiang, Peter William Collins, Brahm Goldstein, István Takács, and Shouryadeep Srivastava
- Subjects
safety ,Adult ,medicine.medical_specialty ,polysialic acid ,haemophilia A ,030204 cardiovascular system & hematology ,Hemophilia A ,Recombinant factor viii ,Gastroenterology ,03 medical and health sciences ,recombinant FVIII ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Humans ,In patient ,tolerability ,Clinical Haemophilia ,Adverse effect ,Genetics (clinical) ,Factor VIII ,biology ,business.industry ,Immunogenicity ,Original Articles ,Hematology ,General Medicine ,Recombinant Proteins ,Cohort ,Sialic Acids ,biology.protein ,Original Article ,Severe haemophilia A ,Antibody ,business ,pharmacokinetics ,030215 immunology - Abstract
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
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- 2019
14. Performance of a clinical risk prediction model for inhibitor formation in severe haemophilia A
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Flora Peyvandi, Mohsen Saleh Elalfy, Roberta Palla, Carla Valsecchi, Vijay Ramanan, Samantha C. Gouw, Frits R. Rosendaal, Shermarke Hassan, Isabella Garagiola, Mehran Karimi, Amal El-Beshlawy, Pier Mannuccio Mannucci, Peyman Eshghi, Paediatric Haematology, and Amsterdam Reproduction & Development (AR&D)
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Oncology ,Risk ,medicine.medical_specialty ,Calibration (statistics) ,Haemophilia A ,Population ,haemophilia A ,030204 cardiovascular system & hematology ,Gene mutation ,immunogenicity ,Haemophilia ,Hemophilia A ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,inhibitors ,medicine ,Humans ,Family history ,education ,Clinical Haemophilia ,Genetics (clinical) ,education.field_of_study ,business.industry ,Hematology ,General Medicine ,Original Articles ,prediction ,medicine.disease ,factor VIII ,Calibration ,Mutation ,Severe haemophilia A ,Original Article ,business ,Predictive modelling ,030215 immunology - Abstract
Background There is a need to identify patients with haemophilia who have a very low or high risk of developing inhibitors. These patients could be candidates for personalized treatment strategies. Aims The aim of this study was to externally validate a previously published prediction model for inhibitor development and to develop a new prediction model that incorporates novel predictors. Methods The population consisted of 251 previously untreated or minimally treated patients with severe haemophilia A enrolled in the SIPPET study. The outcome was inhibitor formation. Model discrimination was measured using the C-statistic, and model calibration was assessed with a calibration plot. The new model was internally validated using bootstrap resampling. Results Firstly, the previously published prediction model was validated. It consisted of three variables: family history of inhibitor development, F8 gene mutation and intensity of first treatment with factor VIII (FVIII). The C-statistic was 0.53 (95% CI: 0.46-0.60), and calibration was limited. Furthermore, a new prediction model was developed that consisted of four predictors: F8 gene mutation, intensity of first treatment with FVIII, the presence of factor VIII non-neutralizing antibodies before treatment initiation and lastly FVIII product type (recombinant vs. plasma-derived). The C-statistic was 0.66 (95 CI: 0.57-0.75), and calibration was moderate. Using a model cut-off point of 10%, positive- and negative predictive values were 0.22 and 0.95, respectively. Conclusion Performance of all prediction models was limited. However, the new model with all predictors may be useful for identifying a small number of patients with a low risk of inhibitor formation.
- Published
- 2021
15. Efficacy and safety of subcutaneous prophylaxis with dalcinonacog alfa in adults with haemophilia B
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Howard Levy, Frank Del Greco, Martin Lee, and Johnny Mahlangu
- Subjects
Adult ,Male ,medicine.medical_specialty ,Clinical Trials and Supportive Activities ,Clinical Sciences ,Thrombogenicity ,haemophilia B ,030204 cardiovascular system & hematology ,immunogenicity ,Haemophilia ,Hemophilia A ,Hemophilia B ,03 medical and health sciences ,0302 clinical medicine ,dalcinonacog alfa ,Pharmacokinetics ,Clinical Research ,Internal medicine ,medicine ,Humans ,Haemophilia B ,Dosing ,Clinical Haemophilia ,Genetics (clinical) ,Clotting factor ,factor IX ,business.industry ,Evaluation of treatments and therapeutic interventions ,clinical trial ,Original Articles ,General Medicine ,Hematology ,medicine.disease ,Clinical trial ,Tolerability ,Cardiovascular System & Hematology ,6.1 Pharmaceuticals ,Original Article ,subcutaneous ,Blood Coagulation Tests ,prophylaxis ,business ,030215 immunology ,Half-Life - Abstract
AimPhase 2b study to assess efficacy, safety, thrombogenicity, immunogenicity and tolerability with 28days 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
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- 2021
16. Adherence to prophylaxis and its association with activation of self-management and treatment satisfaction
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Hoefnagels, J.W., Schrijvers, L.H., Leebeek, F.W.G., Eikenboom, J., Schols, S.E.M., Smit, C., Schutgens, R.E.G., Gouw, S.C., Fischer, K., Haemophilia Netherlands 6 Steering, Hematology, Paediatric Haematology, and ARD - Amsterdam Reproduction and Development
- Subjects
Adult ,medicine.medical_specialty ,Adolescent ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,haemophilia ,Personal Satisfaction ,030204 cardiovascular system & hematology ,treatment satisfaction ,Hemophilia A ,Haemophilia ,Hemophilia patient ,compliance ,Medication Adherence ,Treatment satisfaction ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Surveys and Questionnaires ,Internal medicine ,patient activation ,medicine ,Humans ,In patient ,adherence ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Patient Activation Measure ,Self-management ,business.industry ,Self-Management ,Infant, Newborn ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Regimen ,Cross-Sectional Studies ,Original Article ,business ,030215 immunology - Abstract
Contains fulltext : 237722.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Prophylactic replacement therapy (prophylaxis) in patients with haemophilia (PWH) requires lifelong, frequent (self)infusions. Prophylaxis effectiveness depends on adherence, and the drivers of treatment adherence among PWH are unclear. AIM: To quantify prophylaxis adherence and associations between adherence and patients' treatment attitudes and satisfaction in a large cohort of children and adults with haemophilia. METHODS: In a nationwide, cross-sectional, questionnaire-based study, PWH with complete information currently using prophylaxis were selected. Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis (VERITAS-Pro; normalised score range: 0-100, optimum 0) measured treatment adherence; the Patient Activation Measure (PAM-13; total score range 0-100, optimum 100) measured activation of self-management; Hemophilia Patient Satisfaction Scale (Hemo-Sat; range 0-100, optimum 0) measured treatment satisfaction. Groups were compared according to age (children: 18 years) and adherence levels using non-parametric tests, and correlations were assessed using Spearman's rho. RESULTS: Among 321 participants (median age 33 years, interquartile range [IQR]:15-54 years), adherence was high (median VERITAS-Pro total score 17, 89% adherent) but worsened with age, with median scores of 5, 14 and 20 in children, adolescents, adults, respectively (p
- Published
- 2021
17. A tailored intervention for illness acceptance improves adherence and quality of life in adults with haemophilia using prophylaxis
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Krista Fischer, Mariette H. E. Driessens, Johanna Wilhelmina Hoefnagels, L. H. Schrijvers, and Ruud A. T. Bos
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Adult ,medicine.medical_specialty ,haemophilia ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Affect (psychology) ,Acceptance and commitment therapy ,Illness perceptions ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Intervention (counseling) ,medicine ,Humans ,adherence ,Acceptance and Commitment Therapy ,Clinical Haemophilia ,intervention ,Genetics (clinical) ,Aged ,business.industry ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,Tailored Intervention ,illness acceptance ,Bodily pain ,quality of life ,Physical therapy ,Original Article ,business ,030215 immunology - Abstract
Introduction Adherence to prophylactic treatment (prophylaxis) in persons with haemophilia is challenging and has been reported at only ±50%. Acceptance problems are one of the main reasons for non‐adherence in haemophilia. An evidence‐based intervention was developed based on an acceptance and commitment therapy (ACT) approach. Aim To evaluate a tailored intervention focused on illness acceptance in adults with haemophilia who were prescribed prophylaxis. Methods A pre‐post study was executed in adults with haemophilia who were prescribed prophylaxis. A series of 8 2‐hour group trainings were held, including 3‐8 participants/series. Adherence (VERITAS‐Pro, optimum 0), health‐related quality of life (HRQoL, SF‐36, optimum 100) and illness perception (BIPQ, optimum 0) were measured at start, after six months and 12 months and analysed using Wilcoxon signed‐rank test. Results Twenty‐four patients (median age 47 years, range 27‐74) were included. After 12 months, adherence improved in 68% of patients, quality of life in 48% and illness perception in 31%. Adherence (total score) improved from 35 to 25 (P
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- 2021
18. A multicentre, open‐label study of emicizumab given every 2 or 4 weeks in children with severe haemophilia A without inhibitors
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Masashi Taki, Takashi Suzuki, Sayaka Nagami, Keiji Nogami, Midori Shima, Akira Ishiguro, Seitaro Yoshida, and Koichiro Yoneyama
- Subjects
Male ,medicine.medical_specialty ,Thrombotic microangiopathy ,Haemophilia A ,haemophilia A ,030204 cardiovascular system & hematology ,Antibodies, Monoclonal, Humanized ,Hemophilia A ,Drug Administration Schedule ,paediatrics ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,Antibodies, Bispecific ,Injection site reaction ,medicine ,Humans ,Clinical Haemophilia ,Child ,Adverse effect ,Genetics (clinical) ,Emicizumab ,emicizumab ,Dose-Response Relationship, Drug ,biology ,business.industry ,Infant ,Original Articles ,Hematology ,General Medicine ,medicine.disease ,Confidence interval ,bispecific antibody ,non‐inhibitor ,Child, Preschool ,biology.protein ,Original Article ,Female ,prophylaxis ,Safety ,Antibody ,business ,030215 immunology - Abstract
Introduction Emicizumab is a recombinant humanized bispecific monoclonal antibody mimicking the cofactor function of activated factor VIII. Aim In this multicentre, open‐label study (HOHOEMI), we evaluated the efficacy, safety and pharmacokinetics of emicizumab in Japanese paediatric patients aged
- Published
- 2019
19. Burden of mild haemophilia A: Systematic literature review
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Mimi C. Lee, Wing Yen Wong, Jennifer Quinn, Flora Peyvandi, Fatemeh Tavakkoli, Benjamin Kim, Diana Frame, and Adebayo Lawal
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Adult ,acute bleeding ,medicine.medical_specialty ,Adolescent ,Population ,haemophilia ,Disease ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,disease burden ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Health care ,Humans ,Medicine ,Clinical Haemophilia ,Intensive care medicine ,education ,Genetics (clinical) ,Disease burden ,education.field_of_study ,business.industry ,Original Articles ,Hematology ,General Medicine ,medicine.disease ,Systematic review ,quality of life ,Original Article ,Observational study ,business ,030215 immunology - Abstract
Introduction Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. Aim To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. Methods Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (≥13 years of age) with mild HA. Results Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966‐2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta‐analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF‐36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. Conclusion Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under‐represented and unmet needs may remain unaddressed. As paradigm‐changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality.
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- 2019
20. UK vs US physician decision‐making in the treatment of haemophilia
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Kalle Lyytinen, Christopher C. Lamb, and Adrian Wolfberg
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Adult ,Male ,medicine.medical_specialty ,Clinical Decision-Making ,MEDLINE ,haemophilia ,Physician Decision ,Sample (statistics) ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Grounded theory ,03 medical and health sciences ,0302 clinical medicine ,US HCS vs UK HCS ,Physicians ,medicine ,Humans ,physician decision process ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Evidence-Based Medicine ,business.industry ,Original Articles ,Hematology ,General Medicine ,Evidence-based medicine ,medicine.disease ,United Kingdom ,United States ,Influencer marketing ,Family medicine ,Female ,Original Article ,decision‐making ,business ,030215 immunology ,Qualitative research - Abstract
Introduction Patient–physician shared decision‐making (SDM) has become increasingly seen as having a positive effect on management of chronic diseases. However, little is known of the factors that encourage SDM or how effective it may be at improving health outcomes or how cost‐effective it is. Aim To investigate the uses and applications of patient physician–SDM in the management of haemophilia and the influence of healthcare systems in the United States and the United Kingdom. Methods This was a qualitative study based on interviews with treatment experts in the United States and United Kingdom. A grounded theory approach was used to analyse the data from the transcribed interviews and themes that emerged as related to the decision influencers. Twelve physicians from each country were interviewed by the author. Results Treatment guidelines were viewed as having only limited applicability because of the lack of universal best options in haemophilia. The US physicians in the sample appeared to be more influenced by patient preferences than physicians in the UK, who instead tended to follow policies and standards of care more closely. Physicians in both countries commented that many of their patents had become highly knowledgeable of their bleeding disorder. US physicians were sometimes limited by insurance company policies but also reported that they were often successful in appealing insurance decisions. Conclusion The research suggests that there are different influences on decision‐making between healthcare systems; patients and overarching healthcare systems play a major role in how physicians treat haemophilia.
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- 2019
21. Health‐related quality of life and health status in persons with haemophilia A with inhibitors: A prospective, multicentre, non‐interventional study (NIS)
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Michaela Lehle, Rebecca Kruse-Jarres, Claudia Garcia, Michael Recht, Johnny Mahlangu, Peter Trask, Michael U. Callaghan, Renchi Yang, Johannes Oldenburg, Sylvia von Mackensen, Midori Shima, Maria Elisa Mancuso, Elina Asikanius, Gallia G. Levy, and Harrison Macharia
- Subjects
Adult ,Male ,Work ,Pediatrics ,medicine.medical_specialty ,non‐interventional ,Adolescent ,Visual analogue scale ,Health Status ,Haemophilia A ,Psychological intervention ,haemophilia ,Hemorrhage ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,Absenteeism ,inhibitors ,Humans ,Medicine ,Prospective Studies ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Aged ,Schools ,health‐related quality of life ,business.industry ,Clinical study design ,Standard treatment ,Hematology ,General Medicine ,Middle Aged ,alloantibodies ,medicine.disease ,Hospitalization ,Cohort ,Quality of Life ,Female ,Original Article ,ORIGINAL ARTICLES ,business ,030215 immunology - Abstract
Introduction Real-world data (RWD) on health-related outcomes in persons with haemophilia A (PwHA) provide insights into patient needs and can guide clinical study design. A global, prospective, non-interventional study (NIS; NCT02476942) collected detailed RWD on bleeding outcomes, health-related quality of life (HRQoL) and health status in PwHA treated per local routine clinical practice. Aim To report HRQoL and health status in the adult/adolescent PwHA with inhibitors cohort in the NIS. Methods This cohort enrolled PwHA aged ≥12 years with high-titre factor VIII inhibitor history. Participants remained on their usual treatment (no protocol-specified interventions). Health-related outcomes: Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), Haemophilia-specific Quality of Life Questionnaire for Children Short Form (Haemo-QoL SF), EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) index utility score (IUS) and visual analogue scale (EQ-VAS). Results One hundred three participants were enrolled on episodic (n = 75) or prophylactic treatment (n = 28); median (range) age, 31 (12-75) years; median (range) observation time, 26 (4-70) weeks. Haem-A-QoL scores indicated impairments in HRQoL aspects; comparable between episodic/prophylactic regimens and relatively consistent over time. Haemo-QoL SF scores with both regimens varied over time, and appeared poorer with episodic than prophylactic treatment. IUS and EQ-VAS were comparable between regimens, stable over time and lower on bleeding days. Mean proportions of missed work and school days were 16% and 23%, respectively; mean (standard deviation) number of days hospitalized was 3.2 (8.8) (comparable between groups). Conclusions These RWD demonstrate that PwHA with inhibitors have impaired HRQoL, despite standard treatment, and that more effective treatment options are needed.
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- 2019
22. From the voices of people with haemophilia A and their caregivers: Challenges with current treatment, their impact on quality of life and desired improvements in future therapies
- Author
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Nicole Graham, Charles P. Khoury, Ryan E. Wiley, Marni Williams, Lori Laudenbach, Cindy Milne-Wren, David Page, Jayson M. Stoffman, and Adrian W.K. Snihur
- Subjects
Adult ,Male ,Work ,Haemophilia A ,haemophilia ,030204 cardiovascular system & hematology ,Haemophilia ,Health outcomes ,Hemophilia A ,Recombinant factor viii ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,psychological well‐being ,Nursing ,medicine ,Humans ,adherence ,Clinical Haemophilia ,Genetics (clinical) ,Factor VIII ,treatment ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Focus group ,Treatment Outcome ,quality of life ,Caregivers ,Psychological well-being ,employment ,Original Article ,Female ,ORIGINAL ARTICLES ,business ,Psychosocial ,030215 immunology - Abstract
Introduction Haemophilia A is a chronic disease requiring frequent intravenous infusions of recombinant factor VIII. Previous studies have shown that challenges associated with current treatments may have significant impacts on quality of life (QoL) that are as important as the health outcomes conferred by the therapy. Emerging therapeutic innovations offer the potential to mitigate treatment-related challenges, and it is therefore important to develop a better understanding of patient and caregiver experiences with existing haemophilia A treatments in order to characterize the full value of new treatments. Aim To gather firsthand perspectives from people with haemophilia A (PWHA) and caregivers on the challenges with current treatment, their impact on QoL and desired improvements in future therapies. Methods Qualitative insights were gathered from 20 non-inhibitor PWHA or caregivers of PWHA across Canada through one-on-one interviews; insights were further explored through focus group sessions to uncover overarching themes and prioritize issues with current treatments. Results PWHA and caregivers identified several challenges, including administration of intravenous infusions, coordination of treatment schedules and ensuring adequate medication and supplies. Participants described how these challenges impact psychosocial well-being, physical health, personal/social life and work. Alternate modes of administration and longer-lasting treatment effects were identified as desired improvements over current treatments. Conclusion This study emphasizes the impact that existing haemophilia A treatments have on psychological well-being, employment opportunities and adherence to treatment regimens. These considerations may help to inform decision-making for policymakers and health systems around the true value of new therapies entering the haemophilia market.
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- 2019
23. Efficacy and safety of prophylaxis with BAY 81‐8973 in Chinese patients with severe haemophilia A enrolled in the LEOPOLD II trial
- Author
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Yongqiang Zhao, Despina Tseneklidou-Stoeter, Xuefeng Wang, Jing Sun, Renchi Yang, Nikki Church, Junde Wu, and Depei Wu
- Subjects
Adult ,Male ,medicine.medical_specialty ,China ,Adolescent ,Recombinant human factor VIII ,Population ,haemophilia ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Limited access ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,education ,Adverse effect ,Clinical Haemophilia ,Child ,Genetics (clinical) ,education.field_of_study ,Chinese ,Factor VIII ,business.industry ,clinical trial ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,BAY 81‐8973 ,Clinical trial ,Treatment Outcome ,Severe haemophilia A ,Original Article ,prophylaxis ,ORIGINAL ARTICLES ,Safety ,business ,Bay ,030215 immunology - Abstract
Introduction BAY 81-8973 (Kovaltry® ) is a full-length, unmodified recombinant human factor VIII approved in China for prophylaxis and on-demand treatment in patients with haemophilia A. Limited access to FVIII prophylaxis in China has historically led to this population being undertreated. This subanalysis of LEOPOLD II investigated whether the efficacy and safety of BAY 81-8973 varied between Chinese and non-Chinese patients. Aim To evaluate BAY 81-8973 efficacy and safety in Chinese patients. Methods LEOPOLD II enrolled males aged 12-65 years with severe haemophilia A who were receiving on-demand treatment. Patients were randomly assigned to receive BAY 81-8973 as low-dose prophylaxis (20-30 IU/kg twice-weekly), high-dose prophylaxis (30-40 IU/kg 3 times weekly) or on-demand for 1 year. Results Data were available from 23 Chinese and 57 non-Chinese patients; Chinese patients had a higher prestudy bleeding rate and were more likely to have target joints than non-Chinese patients. 74% of patients were assigned to prophylaxis. Annualized bleeding rates (ABRs) in Chinese and non-Chinese patients receiving prophylaxis were significantly lower compared to patients treated on-demand. Median ABRs for all bleeds in the last 6 months of the study were 2.0 and 1.0 for Chinese and non-Chinese patients, respectively, in the combined prophylaxis groups, and 61.3 and 58.5 in the on-demand group. A treatment-related adverse event occurred in 1 Chinese patient; no patients developed FVIII inhibitors. Conclusion BAY 81-8973 prophylaxis was efficacious and well tolerated in Chinese patients with severe haemophilia A, with ABRs comparable to those in non-Chinese patients receiving prophylaxis.
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- 2019
24. Population‐based surveillance of haemophilia and patient outcomes in Indiana using multiple data sources
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Scott D. Grosse, Amanda I. Okolo, Amy D. Shapiro, Isaac A. Janson, Chris Roberson, Martha Allen, and J. M. Soucie
- Subjects
Adult ,Male ,Indiana ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Oncology clinic ,haemophilia ,Population based ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Epidemiology ,medicine ,Humans ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Aged ,Retrospective Studies ,business.industry ,Public health ,Incidence (epidemiology) ,Medical record ,public health ,Hematology ,General Medicine ,Middle Aged ,medicine.disease ,haemophilia treatment centres ,Multiple data ,Child, Preschool ,Epidemiological Monitoring ,surveillance ,Female ,Original Article ,epidemiology ,ORIGINAL ARTICLES ,business ,030215 immunology - Abstract
Introduction Epidemiological surveillance of haemophilia through linkage of medical records within a US state has not been conducted in 20 years. Aim The Indiana Haemophilia Surveillance Project aims to identify all persons with haemophilia who resided in Indiana in 2011-2013 and to determine the percentage of patients in Indiana cared for at a federally recognized haemophilia treatment centre (HTC). Methods A retrospective review of medical charts was conducted to identify haemophilia cases during the surveillance years. Case-finding methods involved a variety of medical care resources including hospitals, administrative claims data and haematology/oncology clinic reports. Results In Indiana, 704 unique haemophilia cases were identified. Of those cases, 456 (64.8%) had factor VIII and 248 (35.2%) had factor IX deficiency. Among those with known severity levels (n = 685), 233 (34%) were severe, 185 (27%) were moderate, and 267 (39%) were mild. Overall, 81.7% of the haemophilia patients identified visited an HTC at least once during the three-year study period, which was the requirement for being considered an HTC patient. Age-adjusted prevalence for 2013 was 19.4 haemophilia cases per 100 000 males, 12.7 per 100 000 for factor VIII and 6.7 per 100 000 for factor IX. Incidence of haemophilia over the 10 years prior to the surveillance years was 1:3688 live male births in Indiana. During the surveillance years, 24 cases (3.4%) died. Conclusion We observed higher incidence and prevalence of haemophilia in Indiana compared to previous national estimates, as well as higher HTC utilization among persons with haemophilia.
- Published
- 2019
25. Health‐related quality of life in paediatric haemophilia B patients treated with rIX‐FP
- Author
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Wilfried Seifert, Jinesh Shah, Sylvia von Mackensen, and Gili Kenet
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Recombinant Fusion Proteins ,Group ii ,030204 cardiovascular system & hematology ,treatment satisfaction ,Hemophilia B ,Drug Administration Schedule ,Treatment satisfaction ,Factor IX ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,responder definitions ,Medicine ,Humans ,Haemophilia B ,extended half‐life product ,Clinical Haemophilia ,Child ,Exercise ,Genetics (clinical) ,Serum Albumin ,Paediatric patients ,Health related quality of life ,Hemo‐SatP ,health‐related quality of life ,business.industry ,Coagulants ,Haemo‐QoL ,Hematology ,General Medicine ,medicine.disease ,Physical activity level ,Regimen ,Caregivers ,minimal important difference ,Child, Preschool ,Quality of Life ,Original Article ,ORIGINAL ARTICLES ,business ,030215 immunology - Abstract
Introduction Frequent infusions and bleeds can impact on the health-related quality of life (HRQoL) of paediatric haemophilia B patients. rIX-FP (IDELVION® ) is a fusion protein linking recombinant factor IX with recombinant albumin, and is associated with low bleeding rates with a weekly regimen, which could improve HRQoL. Aims To measure the effect of rIX-FP prophylaxis on the HRQoL of paediatric patients and treatment satisfaction in their caregivers using the Haemo-QoL and Hemo-SATP questionnaires, respectively. Methods At baseline and end-of-study (EOS), patients 4-11 years old participating in the PROLONG-9FP program answered the Haemo-QoL questionnaire and gave information on their socio-demographic data and physical activity. Caregivers completed the Hemo-SatP . Minimal important differences (MID) (|Cohen's d| > 0.5) between baseline and EOS and the number of responders (patients with meaningful subject-level improvements over time) at EOS were calculated. Results Twenty patients (age group I: 4-7 years old [n = 12]; age group II: 8-12 years old [n = 8]) completed the Haemo-QoL questionnaire at baseline. MIDs were found in age group I representing improvement for "physical health" (d = -0.547) domain; 60% of patients were responders for "physical health." In age group II, MIDs were seen in most domains; 71.4% patients were responders in "total score." In caregivers, improvements were seen for most domains of the Hemo-SatP with a small effect size. Fewer patients missed school when treated with rIX-FP and 94.1% patients maintained their physical activity level. Conclusion Prophylaxis with rIX-FP led to substantial improvements in HRQoL in paediatric patients and treatment satisfaction in caregivers.
- Published
- 2018
26. Results of a randomized phase III/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery
- Author
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Vasily Mamonov, Bruce Ewenstein, Jerzy Windyga, Srilatha Tangada, Jennifer Doralt, Ingrid Pabinger, Gerald Spotts, and Werner Engl
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Haemophilia A ,Knee replacement ,haemophilia A ,Blood volume ,030204 cardiovascular system & hematology ,Hemophilia A ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Orthopedic Procedures ,intravenous infusion ,Clinical Haemophilia ,Adverse effect ,Genetics (clinical) ,Hip surgery ,Hemostasis ,recombinant factor VIII ,Factor VIII ,business.industry ,clinical trial ,Original Articles ,Hematology ,General Medicine ,Perioperative ,medicine.disease ,Recombinant Proteins ,Confidence interval ,Anesthesia ,Orthopedic surgery ,Original Article ,orthopaedic surgery ,Blood Coagulation Tests ,business ,030215 immunology - Abstract
Introduction In patients with haemophilia A undergoing surgery, factor VIII (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative to bolus infusion (BI). Aim To compare the perioperative haemostatic efficacy and safety of antihaemophilic factor (recombinant) (ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA) CI or BI administration. Methods In this multicentre, phase III/IV, controlled study (NCT00357656), 60 previously treated adult patients with severe or moderately severe disease undergoing elective unilateral major orthopaedic surgery (knee replacement, n = 48; hip surgery, n = 4; other, n = 8) requiring drain placement were randomized to receive antihaemophilic factor (recombinant) CI (n = 29) or BI (n = 31) through postoperative day 7. Primary outcome measure was cumulative packed red blood cell (PRBC)/blood volume in the drainage fluid within 24 h after surgery, used to establish non‐inferiority of CI to BI. Results CI:BI ratio of cumulative PRBC volume in the 24‐h drainage fluid was 0.92 (p‐value
- Published
- 2021
27. Patients' and parents' satisfaction with, and preference for, haemophilia A treatments: a cross-sectional, multicentre, observational study
- Author
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Soon Ki Kim, Sang Kyu Park, Ji Yoon Kim, Goon Jae Cho, Young Shil Park, Hee Jo Baek, Young Joo Kim, Ji Soo Shin, Chung-Mo Nam, Tai Ju Hwang, Jiyu Sun, Ki Young Yoo, and Ho-Jin Lee
- Subjects
Parents ,medicine.medical_specialty ,Haemophilia A ,haemophilia ,Personal Satisfaction ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Treatment satisfaction ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Child ,Clinical Haemophilia ,preference ,Genetics (clinical) ,Paediatric patients ,treatment ,business.industry ,Infant, Newborn ,satisfaction ,Patient Preference ,Hematology ,General Medicine ,Original Articles ,medicine.disease ,Patient preference ,Treatment characteristics ,Preference ,Cross-Sectional Studies ,Patient Satisfaction ,factor VIII ,Physical therapy ,Observational study ,Original Article ,business ,030215 immunology - Abstract
Introduction Reports on patients' satisfaction and preferred characteristics for treatments would be worthwhile when choosing an optimal treatment reflecting patients' perspectives. Aim To identify the characteristics and treatment patterns of patients with haemophilia A, or their caregivers, in Korea and explore patient preferences and satisfaction with their treatment. Methods This cross-sectional, multicentre, observational study was conducted from April 2018 to September 2019 at six nationwide hospitals and three Korea Hemophilia Foundation clinics. Patients aged ≥16 years, or legal caregivers of paediatric patients, who had used factor VIII (FVIII) concentrates for ≥1 month were enrolled. Satisfaction with treatment was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM); preference was evaluated using discrete choice experiment (DCE), with 10 series of two hypothetical treatment options created from D-efficient block design, which varied across five attributes. Results Overall, 505 patients (mean age 31 years) were enrolled in the study. Patients had received FVIII concentrate for an average of 102.9 months (prophylaxis: 53.5%; on-demand: 22.2%). Mean TSQM scores were 64.6 (effectiveness domain), 97.9 (side effects), 57.1 (convenience) and 66.8 (global satisfaction). The number of vials per injection, and the frequency of drug administration, was significantly associated with treatment satisfaction. According to DCE, simpler treatment options were preferred by patients/caregivers. Conclusion The lowest satisfaction levels were shown in the treatment convenience domain. Patients/parents preferred simpler and easier treatment characteristics. In an attempt to enhance the overall satisfaction of patients and caregivers with treatment, consideration of more convenient characteristics is required in future decisions regarding treatment selection.
- Published
- 2021
28. Evidence of a disability paradox in patient‐reported outcomes in haemophilia
- Author
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Jamie O'Hara, Brian O'Mahony, Nanxin Li, George Morgan, Eileen K. Sawyer, Brendan Mulhern, Michelle Witkop, Mark W. Skinner, Diane J. Nugent, Tyler W. Buckner, and Antony P. Martin
- Subjects
Cost effectiveness ,Health Status ,Population ,haemophilia ,Sample (statistics) ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,medicine ,Humans ,Patient Reported Outcome Measures ,Clinical Haemophilia ,education ,Genetics (clinical) ,health equity ,education.field_of_study ,business.industry ,Minimal clinically important difference ,1103 Clinical Sciences ,Original Articles ,cost‐effectiveness ,Hematology ,General Medicine ,medicine.disease ,Preference ,Health equity ,quality of life ,Cardiovascular System & Hematology ,Original Article ,business ,patient‐reported outcome measurement ,030215 immunology ,Demography - Abstract
IntroductionPeople with inherited and long-term conditions such as haemophilia have been shown to adapt to their levels of disability, often reporting better quality of life (QoL) than expected from the general population (the disability paradox).AimTo investigate the disability paradox in people with haemophilia in the United States by examining preference differences in health state valuations versus the general population.MethodsWe conducted a discrete choice experiment including duration to capture valuations of health states based on patient-reported preferences. Participants indicated their preferences for hypothetical health states using the EQ-5D-5L, where each participant completed 15 of the 120 choice tasks. Response inconsistencies were evaluated with dominated and repeated scenarios. Conditional-logit regressions with random sampling of the general population responses were used to match the sample of patients with haemophilia. We compared model estimates and derived preferences associated with EQ-5D-5L health states.ResultsAfter removing respondents with response inconsistencies, 1327/2138 (62%) participants remained (177/283 haemophilia; 1150/1900 general population). Patients with haemophilia indicated higher preference value for 99% of EQ-5D-5L health states compared to the general population (when matched on age and gender). The mean health state valuation difference of 0.17 indicated a meaningful difference compared to a minimal clinically important difference threshold of 0.07. Results were consistent by haemophilia type and severity.ConclusionOur findings indicated the presence of a disability paradox among patients with haemophilia, who reported higher health states than the general population, suggesting the impact of haemophilia may be underestimated if general population value sets are used.
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- 2021
29. The SLIM study-Shared medical appointments to change lifestyles of overweight people with haemophilia: A randomized multiple baseline (n-of-1) design
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Britta A P Laros-van Gorkom, Johanna W M van Wanroij, Marcel A L Hendriks, Maria W.G. Nijhuis-van der Sanden, and Thomas J. Hoogeboom
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Male ,N of 1 trial ,medicine.medical_specialty ,medicine.medical_treatment ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,Haemophilia A ,physical activity ,030204 cardiovascular system & hematology ,Overweight ,Hemophilia A ,Haemophilia ,behaviour therapies ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Group psychotherapy ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,medicine ,Humans ,Hemophilia ,Clinical Haemophilia ,Exercise ,Life Style ,dietary habits ,Genetics (clinical) ,Self-management ,business.industry ,Original Articles ,Hematology ,General Medicine ,medicine.disease ,group therapy ,Multiple baseline design ,self‐management ,Physical therapy ,Shared Medical Appointments ,Original Article ,medicine.symptom ,business ,030215 immunology - Abstract
Contains fulltext : 237762.pdf (Publisher’s version ) (Open Access) INTRODUCTION: People with haemophilia suffer from haemophilic joint disease that may result in physical inactivity and overweight. Shared medical appointments (SMAs) might help limit the consequences of haemophilic arthropathy. SMAs are group meetings supervised by one or more healthcare professionals that can be utilized to improve lifestyle. AIM: To evaluate the feasibility and efficacy of SMAs in people with haemophilia to improve physical activity and eating habits. METHODS: A multiple baseline single-case design was used. Overweight people with haemophilia were eligible to participate. Seven weekly SMAs were conducted using multiple behavioural change techniques to improve physical activity and eating habits. Feasibility of SMAs was evaluated using (a) dropout rate, (b) occurrence of adverse events (AEs), (c) adherence rate and (d) patient satisfaction. During 13 weeks, physical activity was measured daily and eating habits were measured three times per week. The efficacy of SMAs was determined using randomization tests and visual data inspection. RESULTS: Out of the six men participating in the study, one participant dropped out. No study-related AEs occurred. The adherence rate of SMAs was 80%, and participants reported to be 'very satisfied' with the SMAs. Randomization tests and visual analyses demonstrated (statistical) improvements in physical activity (p = .03). No effect was found in self-reported eating habits (p = .55). CONCLUSION: Shared medical appointments are feasible in people with haemophilia and appear to improve physical activity. The effect on improving eating habits could not be established. Scientific replication of our approach is warranted to confirm or refute the merit of SMAs in people with haemophilia.
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- 2021
30. Patient perspectives regarding gene therapy in haemophilia: Interviews from the PAVING study
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Isabelle Huys, Steven Simoens, Brett Hauber, Michel Goldman, Kathelijne Peerlinck, Eline van Overbeeke, Catherine Lambert, Sissel Michelsen, Cédric Hermans, UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Service d'hématologie
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medicine.medical_specialty ,Haemophilia ,Opinion ,interviews ,haemophilia ,Qualitative property ,Hemorrhage ,030204 cardiovascular system & hematology ,Interview guide ,Hemophilia A ,Preference ,Gene therapies ,03 medical and health sciences ,Interviews ,0302 clinical medicine ,advanced therapy ,medicine ,Humans ,Clinical Haemophilia ,preference ,Reimbursement, Incentive ,Genetics (clinical) ,Qualitative Research ,attitudes ,business.industry ,Clinical study design ,gene therapies ,opinion ,Health technology ,Hematology ,General Medicine ,Genetic Therapy ,Original Articles ,medicine.disease ,3. Good health ,Advanced therapy ,Ranking ,Family medicine ,Attitudes ,Original Article ,Positive attitude ,business ,030215 immunology ,Qualitative research - Abstract
INTRODUCTION: Exploring patient perceptions regarding gene therapies may provide insights about their acceptability to patients. OBJECTIVE: To investigate opinions of people with haemophilia (PWH) regarding gene therapies. Moreover, this study aimed to identify patient-relevant attributes (treatment features) that influence PWH's treatment choices. METHODS: Semi-structured individual interviews were conducted with Belgian PWH, types A and B. A predefined interview guide included information sections and open, attribute ranking and case questions. Qualitative data were organized using NVivo 12 and analysed following framework analysis. Sum totals of scores obtained in the ranking exercise were calculated per attribute. RESULTS: In total, 20 PWH participated in the interviews. Most participants demonstrated a positive attitude towards gene therapy and were very willing (40%; n = 8) or willing (35%; n = 7) to receive this treatment. The following five attributes were identified as most important to PWH in making their choice: annual bleeding rate, factor level, uncertainty of long-term risks, impact on daily life, and probability that prophylaxis can be stopped. While participants were concerned about the uncertainty regarding long-term safety, most participants were less concerned about uncertainty regarding long-term efficacy. CONCLUSIONS: This qualitative study showed that most PWH have a positive attitude towards gene therapy and that besides efficacy, safety and the related uncertainties, also impact on daily life is important to patients. The identified patient-relevant attributes may be used by regulators, health technology assessment bodies and payers in their evaluation of gene therapies for haemophilia. Moreover, they may inform clinical trial design, pay-for-performance schemes and real-world evidence studies. ispartof: HAEMOPHILIA vol:27 issue:1 pages:129-136 ispartof: location:England status: published
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- 2021
31. Development and testing of the Satisfaction Questionnaire with Intravenous or Subcutaneous Hemophilia Injection and results from the Phase 3 HAVEN 3 study of emicizumab prophylaxis in persons with haemophilia A without FVIII inhibitors
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Niamh M O'Connell, Johnny Mahlangu, Avrita Campinha-Bacote, Michael U. Callaghan, Christine L. Kempton, Markus Niggli, Aric Parnes, Peter Trask, and Ido Paz-Priel
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Pediatrics ,medicine.medical_specialty ,Haemophilia A ,haemophilia A ,Hemorrhage ,Personal Satisfaction ,030204 cardiovascular system & hematology ,treatment satisfaction ,Antibodies, Monoclonal, Humanized ,Hemophilia A ,Treatment satisfaction ,03 medical and health sciences ,0302 clinical medicine ,Patient satisfaction ,Surveys and Questionnaires ,Antibodies, Bispecific ,medicine ,SQ‐ISHI ,Humans ,Clinical Haemophilia ,Genetics (clinical) ,Emicizumab ,emicizumab ,Factor VIII ,business.industry ,questionnaire ,Treatment burden ,Hematology ,General Medicine ,Satisfaction questionnaire ,Original Articles ,medicine.disease ,Corrigenda ,Confidence interval ,Severe haemophilia A ,Original Article ,business ,patient‐reported outcomes ,030215 immunology - Abstract
Introduction Emicizumab is a subcutaneously (SC) administered prophylactic agent for persons with haemophilia A (PwHA). As part of its clinical development, a new instrument was required to measure treatment satisfaction. Aim Describe development of the Satisfaction Questionnaire with Intravenous or Subcutaneous Hemophilia Injection (SQ-ISHI) and its subsequent testing with HAVEN 3 study participants to measure patient satisfaction with emicizumab. Methods To develop the SQ-ISHI, we conducted four rounds of in-person interviews at five qualitative research facilities. Participants aged ≥12 years with moderate or severe haemophilia A, receiving intravenous factor VIII (FVIII) prophylaxis, provided feedback to optimize content understanding, ease of completion and item relevance. The final SQ-ISHI was completed by HAVEN 3 participants who previously received FVIII prophylaxis; baseline scores were compared with those at Week 21 or 25 of emicizumab prophylaxis. Results Sixty-three HAVEN 3 participants were eligible to complete the questionnaire and rate their satisfaction on a scale of 0 ('not at all satisfied') to 10 ('extremely satisfied'). Mean 'overall satisfaction' with previous FVIII prophylaxis at baseline was 6.9 (95% confidence interval [CI]: 6.2 to 7.7) increasing to 8.8 (95% CI: 8.4 to 9.3) at follow-up (Week 21/25 of treatment with emicizumab). The greatest improvement was observed in satisfaction with treatment half-life (mean score at baseline: 5.8 [95% CI: 4.9 to 6.6] vs 8.6 [95% CI: 8.0 to 9.2] at follow-up). Conclusion These results demonstrate that emicizumab prophylaxis leads to greater treatment satisfaction compared with FVIII prophylaxis, reflecting in part the low treatment burden of emicizumab associated with its infrequent, SC administration.
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- 2020
32. Collagen remodelling and plasma ascorbic acid levels in patients suspected of inherited bleeding disorders harbouring germline variants in collagen‐related genes
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Eva Zetterberg, Jens Lykkesfeldt, Maria Rossing, Eva Leinoe, Morten A. Karsdal, Martin Pehrsson, Tina Manon-Jensen, and Marcus Fager Ferrari
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collagen ,medicine.medical_specialty ,medicine.drug_class ,Connective tissue ,Ascorbic Acid ,030204 cardiovascular system & hematology ,Monoclonal antibody ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Clinical Haemophilia ,Gene ,Genetics (clinical) ,Hematology ,business.industry ,Ehlers‐Danlos syndrome ,Original Articles ,General Medicine ,high‐throughput nucleotide sequencing ,medicine.disease ,Ascorbic acid ,Bleeding diathesis ,Germ Cells ,Endocrinology ,medicine.anatomical_structure ,Ehlers–Danlos syndrome ,Mutation ,Original Article ,Ehlers-Danlos Syndrome ,haemorrhage ,business ,Collagen Type V ,030215 immunology - Abstract
IntroductionVariants in collagen-related genes COL1A1, COL3A1, COL5A1 and COL5A2 are associated with Ehlers-Danlos syndrome (EDS), a heterogeneous group of connective tissue disorders strongly associated with increased bleeding. Of patients with incompletely explained bleeding diathesis, a relatively high proportion were shown to harbour at least one heterozygous variant of unknown significance (VUS) in one of these genes, the vast majority without meeting the clinical criteria for EDS.AimTo investigate the functional consequences of the identified variants by assessing the formation and degradation of types I, III and V collagen, in addition to plasma levels of ascorbic acid (AA).MethodsA total of 31 patients harbouring at least one heterozygous VUS in COL1A1, COL3A1, COL5A1 or COL5A2 and 20 healthy controls were assessed using monoclonal antibodies targeting neo-epitopes specific for collagen formation and degradation. Plasma AA levels were measured in patients using high-performance liquid chromatography.ResultsSerum levels of C5 M (degradation of type V collagen) were decreased in patients compared with healthy controls (p = .033). No significant differences were found in biomarkers for remodelling of types I and III collagen. A significant negative correlation between bleeding (ISTH-BAT score) and plasma AA levels was shown (r = −.42; r2 = .17; p = .020). Suboptimal or marginally deficient AA status was found in 8/31 patients (26%).ConclusionFunctional investigations of collagen remodelling were not able to identify any clear associations between the identified variants and increased bleeding. The negative correlation between plasma AA levels and ISTH-BAT score motivates further investigations.
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- 2020
33. Postauthorization safety surveillance study of antihaemophilic factor (recombinant) reconstituted in 2 mL sterile water for injection in children with haemophilia A
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Benoît Guillet, Jan Blatny, Jennifer Doralt, Srilatha Tangada, Gerald Spotts, Bénédicte Wibaut, Freimut H. Schilling, Andras Nagy, Jimena Goldstine, Werner Engl, Jayashree Motwani, Birmingham Children’s Hospital, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Baxalta Innovations GmbH [Vienna, Austria], Baxalta Innovations GmbH, a Takeda company, Vienna, Austria, Baxalta US Inc., a Takeda company, Westlake Village, CA, USA, Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Male ,medicine.medical_specialty ,Antihaemophilic Factor ,[SDV]Life Sciences [q-bio] ,Haemophilia A ,haemophilia A ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Injections ,on-demand ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,paediatric patients ,Adverse effect ,Clinical Haemophilia ,Child ,Genetics (clinical) ,on‐demand ,Safety surveillance ,Administration time ,Factor VIII ,business.industry ,Sterile water ,Infant, Newborn ,Infant ,Water ,Hematology ,General Medicine ,Original Articles ,medicine.disease ,3. Good health ,Tolerability ,Child, Preschool ,Epidemiological Monitoring ,Original Article ,Female ,prophylaxis ,business ,030215 immunology ,antihaemophilic factor (recombinant) - Abstract
International audience; Introduction - Antihaemophilic factor (recombinant) (rAHF; ADVATE ) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion-related reactions, especially in children. Aim - To assess local tolerability, safety and effectiveness of rAHF 2 mL during routine clinical practice factor VIII (FVIII) replacement (on-demand and prophylaxis) in children with severe (FVIII
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- 2020
34. High adherence to prophylaxis regimens in haemophilia B patients receiving rIX-FP: Evidence from clinical trials and real-world practice
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Gili Kenet, Carmen Altisent, Maria Elisa Mancuso, Elena Santagostino, Lisa N. Boggio, Johannes Oldenburg, Wilfried Seifert, and Anthony K.C. Chan
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Adult ,medicine.medical_specialty ,albutrepenonacog alfa ,Adolescent ,Recombinant Fusion Proteins ,Hemorrhage ,haemophilia B ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia B ,Factor IX ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Haemophilia B ,adherence ,Dosing ,Practice Patterns, Physicians' ,Clinical Haemophilia ,Child ,Infusions, Intravenous ,Genetics (clinical) ,Serum Albumin ,Aged ,treatment ,business.industry ,rIX‐FP ,Original Articles ,Hematology ,General Medicine ,Bleed ,Middle Aged ,medicine.disease ,Clinical trial ,Treatment Adherence and Compliance ,Regimen ,Original Article ,business ,Dosing Frequency ,030215 immunology ,medicine.drug - Abstract
Introduction Adherence to prophylaxis regimens is essential for bleed prevention in haemophilia but remains a challenge due to the need for frequent infusions. Aim To evaluate patient adherence to prophylaxis regimens with a long-acting recombinant factor IX (rIX-FP; IDELVION® ) in clinical studies and real-world practice. Methods In two phase 3 clinical studies, patients with haemophilia B (FIX ≤2%) recorded their dose, dosing frequency and rIX-FP consumption in an e-diary. Adherence to prescribed prophylaxis regimens was assessed in all patients and to prescribed dose in patients ≥12 years only. Additionally, adherence to rIX-FP prophylaxis regimens in real-world practice was captured. Results In clinical studies, 94.9% (n = 56/59) of patients ≥12 years and 100% (n = 27) of paediatric patients received ≥80% of the expected number of infusions for their assigned prophylaxis schedule. Overall, mean adherence rate was 95.5% across all prophylaxis regimens in patients ≥12 years and 97.9% with a 7-day regimen in paediatric patients. In patients ≥12 years, 85.7% (n = 54/63) were dose adherent, defined as receiving within 10% of their prescribed dose ≥80% of the time. In real-world practice, adherence was observed in 100% (n = 14 and n = 15, respectively) of patients in two haemophilia treatment centres and 57.1% (n = 4/7) of patients in a third centre; non-adherence (n = 3/7) was linked to insurance-related and parental issues. Conclusion In clinical studies, patients with haemophilia B had high adherence rates to rIX-FP prophylaxis regimens with a variety of dosing intervals, enabling them to achieve very low bleeding rates. High adherence may also be achievable in real-world practice.
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- 2020
35. Social support and resilience in persons with severe haemophilia: An interpretative phenomenological analysis
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Iva Poláčková Šolcová, Robert Brnka, Tekla Horňáková, Zdeněk Meier, Jan Blatný, Kateřina Ratajová, and Peter Tavel
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Adult ,Male ,Coping (psychology) ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_treatment ,education ,Protective factor ,haemophilia ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Group psychotherapy ,03 medical and health sciences ,Social support ,0302 clinical medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Clinical Haemophilia ,resilience ,Genetics (clinical) ,Aged ,Interpretative phenomenological analysis ,Social work ,business.industry ,Social Support ,Peer group ,Hematology ,General Medicine ,Original Articles ,Middle Aged ,Resilience, Psychological ,medicine.disease ,group therapy ,3. Good health ,Female ,Original Article ,individual therapy ,business ,030215 immunology ,Clinical psychology - Abstract
Introduction Haemophilia is a hereditary haemorrhagic disorder characterized by deficiency or dysfunction of coagulation factors. Recurrent joint and muscle bleeds lead to progressive musculoskeletal damage. Haemophilia affects patients physically but also socially and psychologically. Traumatic experiences, chronic stress and illnesses can lead to mental disorders, but many persons with haemophilia maintain a highly positive outlook. Aim To explore qualitatively which coping mechanisms persons with haemophilia use and in what way they help them to live with their diagnosis. Methods We recruited five adults with haemophilia and conducted semi‐structured face‐to‐face interviews. Transcripts were analysed using interpretative phenomenological analysis (IPA). Results Two core themes emerged from the analysis: social support as an external factor and resilience as an internal factor of coping with the disease. Persons with haemophilia usually need help with health‐related complications, and this affects the social support they require. Their wider support network tends to involve family and friends but also healthcare professionals and other specialists. This network provides practical help but also functions as an important psychological protective factor. An unexpected finding was that persons with haemophilia want not only to receive support but are also keen to offer support to others. Conclusion These findings can help identify persons who provide most support to people suffering from haemophilia. Haemophilic centres should include in their teams psychologists and social workers and offer individual and group therapy to their clients, group meetings for friends and families of persons with haemophilia, provide learning resources to teachers aiming to incorporate children with haemophilia in their peer group, and organize Balint groups for physicians, psychologists and other healthcare professionals.
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- 2019
36. Postmarketing safety and effectiveness of recombinant factor IX (nonacog alfa) in Japanese patients with haemophilia B
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Hiromi Yamaguchi, Katsuyuki Fukutake, Tadashi Matsushita, Michio Sakai, Toshiyuki Karumori, Masashi Taki, and Ami Takata
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safety ,Adult ,Male ,nonacog alfa ,medicine.medical_specialty ,Adolescent ,effectiveness ,Postmarketing surveillance ,Hemorrhage ,haemophilia B ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia B ,Factor IX ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Internal medicine ,Product Surveillance, Postmarketing ,medicine ,Humans ,Haemophilia B ,Clinical Haemophilia ,Adverse effect ,Genetics (clinical) ,Aged ,Haemophilic arthropathy ,Bleeding episodes ,business.industry ,Incidence (epidemiology) ,Original Articles ,Hematology ,General Medicine ,Middle Aged ,real‐world ,medicine.disease ,Recombinant Proteins ,Original Article ,Female ,business ,030215 immunology ,Recombinant factor IX - Abstract
Introduction In 2010, nonacog alfa became the first recombinant factor IX (rFIX) available in Japan for patients with haemophilia B. Aim To determine real‐world safety (adverse events, incidence of inhibitors) and effectiveness of nonacog alfa in Japan. Methods This multicentre, prospective, observational, postmarketing surveillance study enrolled previously treated and untreated patients (PTPs and PUPs, respectively) who were observed for 1 and 2 years, respectively, after initiating nonacog alfa therapy. Safety and effectiveness were assessed for each treatment type. Annualized bleeding rate (ABR) and incremental recovery of rFIX were also evaluated. Results Overall, 312 of 314 patients enrolled from 173 sites were eligible for the safety analysis set (PTPs, 281; PUPs, 28; other, 3). Mean age was 25.4 (PTPs) and 14.8 (PUPs) years. Haemophilic severity ranged from mild to severe, and 133 (42.6%) patients had haemophilic arthropathy. Of 285 patients (PTPs, 257; PUPs, 28) in the effectiveness set, 112 received on‐demand treatment for 1161 bleeding episodes (effectiveness rate, 93.7%) and 185 received routine prophylaxis (effectiveness rate, 95.5%). No spontaneous bleeding was observed in 52.4% of patients during prophylactic treatment. Median ABR was lower during routine prophylaxis (2.0) vs the rest of the observation period (8.3). A weak negative correlation was found between body weight and the reciprocal of rFIX recovery. Eleven adverse drug reactions occurred in 7 PTPs (2.2% [7/312]); recurrence of inhibitor was observed in 1 patient, but no new inhibitor developed in PTPs or PUPs. Conclusion Nonacog alfa therapy is safe and effective in the real‐world scenario in Japan.
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- 2019
37. Professional functioning of young adults with congenital coagulation disorders in the Netherlands
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Martha A. Grootenhuis, Marjolein Peters, Lotte Haverman, Marieke J. H. A. Kruip, Perrine F. Limperg, Heleen Maurice-Stam, Jeroen Eikenboom, Michiel Coppens, APH - Methodology, APH - Mental Health, Amsterdam Reproduction & Development (AR&D), Hematology, Orthopedics and Sports Medicine, Paediatric Psychosocial Care, ACS - Pulmonary hypertension & thrombosis, Vascular Medicine, Paediatric Infectious Diseases / Rheumatology / Immunology, AII - Inflammatory diseases, APH - Personalized Medicine, and APH - Quality of Care
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Adult ,Employment ,Male ,young adults ,Gerontology ,impairment ,Adolescent ,Haemophilia A ,haemophilia ,Efficiency ,030204 cardiovascular system & hematology ,Haemophilia ,Logistic regression ,professional functioning ,Young Adult ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,work ,Quality of life ,medicine ,Humans ,Disabled Persons ,In patient ,Young adult ,Clinical Haemophilia ,Genetics (clinical) ,Netherlands ,business.industry ,Hematology ,General Medicine ,Blood Coagulation Disorders ,medicine.disease ,Socioeconomic Factors ,Presenteeism ,Quality of Life ,Absenteeism ,Original Article ,Female ,ORIGINAL ARTICLES ,business ,030215 immunology - Abstract
Introduction and Aim: Suboptimal health-related quality of life and lowered employment rates found in a previous study in young adults (YA) with congenital coagulation disorders (CCD) in the Netherlands underline the need for more insight into professional functioning of YA with CCD and into determinants of professional functioning. Methods: Young adults (18-30 years) with CCD participated in a cross-sectional study. Professional functioning was assessed with the Work Productivity and Activity Impairment questionnaire (WPAI). Potential determinants were assessed with the Course of Life Questionnaire (CoLQ), Pediatric Quality of Life Inventory Young Adult version (PedsQL_YA), Illness Cognition Questionnaire (ICQ) and Haemophilia Activities List (HAL). Logistic regression analyses were performed in the complete sample of YA with CCD, and in YA men with haemophilia separately, to examine determinants of WPAI outcomes. Results: Ninety-four YA (77 men; mean age 24.1 years, SD 3.5 and 17 women; mean age 24.5 years, SD 3.8) with CCD (74% haemophilia A/B) participated. 74.5% of YA were paid employed for on average 30 hours per week. Of these, more than a quarter reported work impairment. Older age and a non-severe type of haemophilia (in the sample of YA men with haemophilia) were associated with successful (paid) employment. No variables were associated with professional functioning (expressed as Presenteeism and Overall work impairment) in patients with CCD or haemophilia. Conclusion: Three-quarters of YA with CCD were successful in finding paid employment. Though absenteeism was low, YA with paid employment needs attention as a considerable part experienced work impairment.
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- 2019
38. BAY 94-9027 prophylaxis is efficacious and well tolerated for up to >5 years with extended dosing intervals: PROTECT VIII extension interim results
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Ho Jin Shin, Pål Andre Holme, Claude Negrier, Shadan Lalezari, Monika Maas Enriquez, Mark T. Reding, Pavani Chalasani, Despina Tseneklidou-Stoeter, Maria Wang, and Ingrid Pabinger
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Adolescent ,Haemophilia A ,Hemorrhage ,haemophilia A ,030204 cardiovascular system & hematology ,Hemophilia A ,Recombinant factor viii ,recombinant proteins ,Polyethylene Glycols ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Internal medicine ,On demand ,medicine ,Humans ,Dosing ,Child ,Clinical Haemophilia ,Genetics (clinical) ,Factor VIII ,Dose-Response Relationship, Drug ,business.industry ,clinical trial ,Hematology ,General Medicine ,Original Articles ,Bleed ,Middle Aged ,medicine.disease ,Clinical trial ,Quartile ,Female ,Original Article ,intravenous infusions ,Safety ,business ,Bay ,030215 immunology - Abstract
Introduction BAY 94-9027 is an extended-half-life, site-specifically PEGylated, B-domain-deleted recombinant factor VIII (FVIII). The PROTECT VIII main study demonstrated efficacy of bleed control using extended-interval prophylaxis with BAY 94-9027 for 36 weeks. Aim To report long-term efficacy and safety of prophylaxis with BAY 94-9027 in a descriptive analysis of the ongoing PROTECT VIII extension with a total treatment time of up to >5 years. Methods Previously treated males aged 12-65 years with severe haemophilia A who completed the PROTECT VIII main study were eligible for the open-label extension. Patients received on-demand treatment or prophylaxis (30-40 IU/kg twice weekly, 45-60 IU/kg every 5 days, or 60 IU/kg every 7 days) and could switch regimens as needed. Results Patients (N = 121; on demand, n = 14; prophylaxis, n = 107) accumulated a median (range) of 3.9 years (297-1965 days) and 223 (23-563) total exposure days by 31 January 2018. During the extension, median (quartile [Q]1; Q3) annualized bleeding rates (ABRs) for total bleeds were 1.6 (0.3; 4.6) for patients receiving prophylaxis and 34.1 (20.3; 36.6) for patients receiving on-demand treatment. ABRs for twice-weekly (n = 23), every-5-days (n = 33), every-7-days (n = 23) and variable frequency (n = 28) treatments were 1.7, 1.2, 0.7 and 3.1, respectively. Of prophylaxis patients, 20.6% were bleed-free throughout the extension (median time, 3.2 years), and 44.5% were bleed-free during the last 6 months. No patients developed FVIII inhibitors. Conclusions BAY 94-9027 prophylaxis was efficacious and well tolerated with dosing intervals up to every 7 days for a median (range) of 3.9 years (0.8-5.4 years).
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- 2019
39. Consensus statements on vaccination in patients with haemophilia—Results from the Italian haemophilia and vaccinations (HEVA) project
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Santagostino E., Riva A., Cesaro S., Esposito S., Matino D., Mazzucchelli R. I., Molinari, Angelo Claudio, Mura R., Notarangelo L. D., Tagliaferri A., Di Minno G., Clerici M., Ambaglio C., Brigida Aru A., Baldacci E., Barillari G., Basso M., Bernasconi S., Bertamino M., Bertoni E., Biasoli C., Federica Biguzzi E., Bonetti E., Borchiellini A., Bulgarelli S., Cabibbo S., Cantori I., Castaman G., Castiglia P., Coluccia A., Coppetelli U., Coppola A., Cultrera D., De Candia E., Delios G., Di Gennaro L., Di Gregorio P., Di Minno M., Dragani A., Pietro Ettorre C., Franchini M., Galli M., Gallo G., Giordano P., Giuffrida G., Iannaccaro P., Lassandro G., Lazzareschi I., Linari S., Luciani M., Macchi S., Malcangi G., Malizia R., Marietta M., Marino R., Massoud M., Gabriella Mazzucconi M., Milan M., Morfini M., Napolitano M., Pasca S., Pedrazzi P., Peyvandi F. A., Piscitelli L., Pollio B., Preti P., Quintavalle G., Radossi P., Raso S., Ricca I., Rocino A., Santoro C., Carlotta Santoro R., Sarolo L., Schiavoni M., Schiavulli M., Sciancalepore P., Luisa Serino M., Mario Siragusa S., Sottilotta G., Svahn J., Valdre L., Cristina Vedovati M., Zanon E., Santagostino, E., Riva, A., Cesaro, S., Esposito, S., Matino, D., Mazzucchelli, R. I., Molinari, Angelo Claudio, Mura, R., Notarangelo, L. D., Tagliaferri, A., Di Minno, G., Clerici, M., Ambaglio, C., Brigida Aru, A., Baldacci, E., Barillari, G., Basso, M., Bernasconi, S., Bertamino, M., Bertoni, E., Biasoli, C., Federica Biguzzi, E., Bonetti, E., Borchiellini, A., Bulgarelli, S., Cabibbo, S., Cantori, I., Castaman, G., Castiglia, P., Coluccia, A., Coppetelli, U., Coppola, A., Cultrera, D., De Candia, E., Delios, G., Di Gennaro, L., Di Gregorio, P., Di Minno, M., Dragani, A., Pietro Ettorre, C., Franchini, M., Galli, M., Gallo, G., Giordano, P., Giuffrida, G., Iannaccaro, P., Lassandro, G., Lazzareschi, I., Linari, S., Luciani, M., Macchi, S., Malcangi, G., Malizia, R., Marietta, M., Marino, R., Massoud, M., Gabriella Mazzucconi, M., Milan, M., Morfini, M., Napolitano, M., Pasca, S., Pedrazzi, P., Peyvandi, F. A., Piscitelli, L., Pollio, B., Preti, P., Quintavalle, G., Radossi, P., Raso, S., Ricca, I., Rocino, A., Santoro, C., Carlotta Santoro, R., Sarolo, L., Schiavoni, M., Schiavulli, M., Sciancalepore, P., Luisa Serino, M., Mario Siragusa, S., Sottilotta, G., Svahn, J., Valdre, L., Cristina Vedovati, M., and Zanon, E.
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Adult ,medicine.medical_specialty ,Consensus ,Delphi Technique ,Vaccination schedule ,Delphi method ,haemophilia ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,immunization ,Hemophilia B ,bleeding disorder ,factor VIII inhibitor ,vaccination ,Child ,Evidence-Based Medicine ,Humans ,Italy ,Vaccination ,03 medical and health sciences ,0302 clinical medicine ,Vaccine administration ,Medicine ,In patient ,Clinical Haemophilia ,Genetics (clinical) ,business.industry ,Original Articles ,Hematology ,General Medicine ,Evidence-based medicine ,medicine.disease ,Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,Immunization ,Family medicine ,Original Article ,business ,030215 immunology - Abstract
Vaccination against communicable diseases is crucial for disease prevention, but this practice poses challenges to healthcare professionals in patients with haemophilia. Poor knowledge of the vaccination requirements for these patients and safety concerns often result in vaccination delay or avoidance. In order to address this issue, a panel of 11 Italian haemophilia and immunization experts conducted a Delphi consensus process to identify the main concerns regarding the safe use of vaccines in patients with haemophilia. The consensus was based on a literature search of the available evidence, which was used by the experts to design 27 consensus statements. A group of clinicians then rated these statements using the 5‐point Likert‐type scale (1 = strongly disagree; 5 = strongly agree). The main issues identified by the expert panel included vaccination schedule for haemophilic patients; protocol and optimal route of vaccine administration; vaccination of haemophilic patients with antibodies inhibiting coagulation factor VIII (inhibitors); and vaccination and risk of inhibitor development. This manuscript discusses these controversial areas in detail supported by the available literature evidence and provides evidence‐ and consensus‐based recommendations. Overall, participants agreed on most statements, except those addressing the potential role of vaccination in inhibitor formation. Participants agreed that patients with haemophilia should receive vaccinations according to the institutional schedule for individuals without bleeding disorders; however, vaccination of patients with haemophilia requires comprehensive planning, taking into account disease severity, type and route of vaccination, and bleeding risk. Data also suggest vaccination timing does not need to take into consideration when the patient received factor VIII replacement.
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- 2019
40. Once-weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8-GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial)
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Pål Andre Holme, Elena Santagostino, Steven R. Lentz, Claude Negrier, Andrea Landorph, Mudi Misgav, Canan Albayrak, Allison P. Wheeler, Miguel A. Escobar, Robert Klamroth, Nicola Curry, Susan Kearney, Sidsel Marie Tønder, Midori Shima, and OMÜ
- Subjects
Adult ,Male ,FVIII ,safety ,medicine.medical_specialty ,Randomization ,Haemophilia A ,efficacy ,Hemorrhage ,haemophilia A ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Drug Administration Schedule ,Polyethylene Glycols ,Recombinant factor VIII N8 ,N8-GP ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,once‐weekly prophylaxis ,Clinical Haemophilia ,Genetics (clinical) ,Factor VIII ,business.industry ,Incidence (epidemiology) ,Hematology ,General Medicine ,Turoctocog alfa ,medicine.disease ,N8‐GP ,once-weekly prophylaxis ,Cohort ,Original Article ,Female ,Severe haemophilia A ,ORIGINAL ARTICLES ,business ,030215 immunology - Abstract
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
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- 2019
41. Measurement of joint health in persons with haemophilia: A systematic review of the measurement properties of haemophilia-specific instruments
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Samantha C. Gouw, Merel A. Timmer, Piet de Kleijn, P. Hilliard, Marjolein Peters, Victor S. Blanchette, Krista Fischer, Alok Srivastava, ACS - Pulmonary hypertension & thrombosis, and Paediatric Infectious Diseases / Rheumatology / Immunology
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medicine.medical_specialty ,validity ,responsiveness ,Databases, Factual ,Haemophilia A ,MEDLINE ,Joints/physiopathology ,haemophilia ,Physical examination ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,Severity of Illness Index ,Databases ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Arthropathy ,medicine ,Journal Article ,Humans ,Genetics(clinical) ,Clinical Haemophilia ,Physical Examination ,Factual ,Genetics (clinical) ,Reliability (statistics) ,reliability ,medicine.diagnostic_test ,business.industry ,Original Articles ,General Medicine ,Hematology ,medicine.disease ,Checklist ,Joint Diseases/etiology ,Hemophilia A/complications ,Physical therapy ,Quality of Life ,Joints ,Original Article ,Joint Diseases ,business ,Physical Examination/methods ,arthropathy ,030215 immunology - Abstract
Introduction: Accurate assessment of joint health in persons with haemophilia is crucial. Several haemophilia-specific measurement tools are available, but an overview of the measurement properties is lacking. Aim: To provide an overview of the measurement properties of haemophilia-specific measurement tools to assess clinical joint health. Methods: MEDLINE and EMBASE were searched for reports on reliability, validity or responsiveness of the World Federation of Haemophilia Orthopedic Joint Score (WFH), Colorado Physical Examination Score (CPE), joint examination score by Petrini (PJS) and Hemophilia Joint Health Score (HJHS). Methodological quality of the studies was assessed using an adapted COSMIN checklist. Results: The search yielded 2905 unique hits, and 98 papers were included. The methodological quality of the included studies was limited. The HJHS was studied most extensively, which yielded limited evidence for good internal consistency and structural validity, moderate evidence for hypothesis testing in adults and conflicting evidence for hypothesis testing in children. Reliability, measurement error and responsiveness were rated unknown due to low COSMIN scores. For the CPE and PJS, we found limited to moderate evidence for good responsiveness and conflicting evidence for hypothesis testing. Conclusion: Only patchy evidence is available on the quality of measurement properties of all haemophilia-specific joint health scores. Although significant gaps in the evidence for all instruments remain, measurement properties of the HJHS were most extensively studied and show no drawbacks for use in clinical practice. This review forms the basis for further research aimed at the assessment of measurement properties of measurement tools to assess joint health.
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- 2019
42. The changing face of immune tolerance induction in haemophilia A with the advent of emicizumab
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Ri Liesner, Elena Santagostino, Carmen Escuriola-Ettingshausen, Manuel Carcao, Guy Young, Angelika Batorova, Beatrice Nolan, Johannes Oldenburg, and Saturnino Haya
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medicine.medical_specialty ,Haemophilia A ,Face (sociological concept) ,haemophilia A ,030204 cardiovascular system & hematology ,Haemophilia ,Antibodies, Monoclonal, Humanized ,Hemophilia A ,Risk Assessment ,Immune tolerance ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Antibodies, Bispecific ,medicine ,Immune Tolerance ,Humans ,Intensive care medicine ,Clinical Haemophilia ,Genetics (clinical) ,bypassing agents ,Emicizumab ,immune tolerance induction ,Factor VIII ,emicizumab ,Dose-Response Relationship, Drug ,business.industry ,Hematology ,General Medicine ,Original Articles ,medicine.disease ,Antibodies, Neutralizing ,inhibitor ,Original Article ,business ,030215 immunology - Abstract
Introduction As a result of the new treatment paradigm that the haemophilia community will face with the availability of novel (non‐factor) therapies, an updated consensus on ITI recommendations and inhibitor management strategies is needed. Aim The Future of Immunotolerance Treatment (FIT) group was established to contemplate, determine and recommend the best management options for patients with haemophilia A and inhibitors. Discussion and Conclusions Despite the considerable success of emicizumab in the management of inhibitor patients, the FIT group still sees the importance of eradicating inhibitors. However, the availability of emicizumab and other non‐factor therapies in the future might impact greatly on how ITI is undertaken. Theoretically, concomitant use of emicizumab and FVIII might allow emicizumab to effectively prevent bleeding with lower dose ITI regimens. This might allow for the greater adoption of low‐dose/low‐frequency FVIII ITI regimens, which may result in a reduced need for central venous access devices while still maintaining a reasonable likelihood of ITI success. The FIT group proposes a new management algorithm for current ITI (without emicizumab) and a hypothetical new approach with the availability of emicizumab. As there are no published data regarding the concomitant use of emicizumab and FVIII for ITI, the FIT Expert group encourages the undertaking of properly conducted prospective studies to explore these approaches further.
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- 2018
43. Newborn screening for haemophilia: The views of families and adults living with haemophilia in the UK
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Felicity K, Boardman, Rachel, Hale, and Philip J, Young
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Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,social implications ,Adolescent ,haemophilia ,bloodspot ,Hemophilia A ,Hemophilia B ,Young Adult ,Neonatal Screening ,hemic and lymphatic diseases ,Surveys and Questionnaires ,Humans ,Family ,genetics ,Genetic Testing ,Clinical Haemophilia ,Aged ,attitudes ,newborn screening ,Infant, Newborn ,Middle Aged ,ethics ,United Kingdom ,Female ,Original Article ,ORIGINAL ARTICLES - Abstract
Introduction As genomic sequencing become more efficient and cost‐effective, the number of conditions identified through newborn screening globally is set to dramatically increase. Haemophilia is a candidate condition; however, very little is known about the attitudes of the haemophilia community towards screening. Aim This study aimed to outline the perspectives of adults with haemophilia and their families towards newborn screening. Methods A paper and online survey on screening were distributed to every family known to the Haemophilia Society UK. Data collection occurred between January and June 2018. In total, 327 participants completed the survey: 76% were a relative of a person with haemophilia and 24% had haemophilia themselves; 83% were living with haemophilia A and 17% with haemophilia B. Results The vast majority supported newborn screening (77%) and preferred it to other forms of screening (preconception or prenatal). Participants supported newborn screening primarily because they viewed it as a means to facilitate early support and treatment, facilitate informed decisions about future pregnancies and prevent the “diagnostic odyssey.” The 23% who did not support the screen did not associate these particular benefits with newborn screening. Conclusion Haemophilia emerged from this analysis as a condition that the vast majority of participants considered a “liveable” disability and one best suited to newborn screening programmes that could improve support to affected families rather than reduce the birth rate of affected children.
- Published
- 2018
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