Treatment patterns, health-related quality of life and adherence to prophylaxis among haemophilia A patients in the United States

Summary. Prophylaxis and adherence to prophylaxis are increasingly recognized as important factors for the health‐related quality of life (HRQOL) of haemophilia patients. This study aims to assess treatment practices over time, HRQOL and adherence among severe haemophilia A patients in the US. Severe haemophilia A patients or their caregivers participated in a 2009 cross‐sectional survey. HRQOL was measured using either PEDS‐QL or SF‐12; adherence was measured using the VERITAS‐Pro. Student t‐tests evaluated differences between children vs. adults and self‐infusion status. A total of 117 respondents participated in the survey, capturing data for 64 adults (mean age = 37.9 years) and 53 children (mean age = 10.5 years). Although 96% of paediatric patients were currently receiving prophylaxis, only 32 (50%) adults reported receiving prophylaxis at some point in their life. Adults who have always been on prophylaxis reported better physical functioning and physical HRQOL (both P < 0.05) than adults who had not. The paediatric group reported better adherence compared to the adult group on the total scale (38 vs. 45.8, P < 0.05). Children <12 years had higher adherence than adolescents 12–18 years old (35.5 vs. 40.8; P < 0.05). Paediatric patients infused by family members showed better adherence than paediatric self‐infusers (P < 0.05). This study showed different treatment patterns between paediatric and adult patients and how the patterns impacted HRQOL. It also provided the first standardized evaluation of adherence using the VERITAS‐Pro in a US national sample. This study enhances understanding of treatment practices and adherence for the US haemophilia population and may offer insight into where adherence can be improved.     

Adherence to treatment in a Western European paediatric population with haemophilia: reliability and validity of the VERITAS‐Pro scale

Treatment adherence in haemophilia is strongly associated with quality of life and the cost–benefit of treatment. Therefore, it is important to quantify and monitor it. This study aimed to validate a translation of the VERITAS‐Pro cross‐culturally and analyse treatment adherence in a Dutch population of paediatric haemophilia patients. Children aged 1–18 years with haemophilia were included from three Haemophilia Treatment Centres, on prophylactic clotting factor replacement therapy for more than 1 year. Parents and adolescents were analysed separately. The adherence scale for prophylactic therapy (VERITAS‐Pro) was translated according to international guidelines. This instrument contains a total of six subscales (‘Time’, ‘Dose’, ‘Plan’, ‘Remember’, ‘Skip’ and ‘Communicate’) each with four items. Lower scores reflect higher adherence. Overall response rate was 85%, leading to a study population of 60 children. Mean age was 10 years (SD 4.1). Internal consistency reliability: Mean Cronbach's alphas were adequate (>0.70) for total score and the subscales ‘Skip’ and ‘Communicate’. Item‐own subscale correlations were stronger than most item‐other subscale correlations. Convergent validity: Total scores were higher for non‐adherent participants compared with adherent participants according to patient infusion logs (n = 48; P < 0.05). Test–retest correlations: Significant for all scales except ‘Dose’ (n = 58; P < 0.01). This study demonstrates applicability of VERITAS‐Pro outside the United States, as total score and most subscales effectively quantified treatment adherence in a Dutch paediatric population on prophylactic therapy. Non‐adherent respondents’ total scores were significantly higher, demonstrating the ability of VERITAS‐Pro to identify non‐adherent individuals.     

Better adherence to prescribed treatment regimen is related to less chronic pain among adolescents and young adults with moderate or severe haemophilia

Little data exist, especially for adolescent and young adult (AYA) persons with haemophilia (PWH), about the relationship between adherence to prescribed treatment regimen and chronic pain. We examined this relationship among PWH (moderate or severe) aged 13–25 via cross‐sectional survey. Adherence was assessed using the Validated Hemophilia Regimen Treatment Adherence Scale (VERITAS)‐Pro and VERITAS‐PRN for prophylactic and on‐demand participants respectively. VERITAS scores range from 24 (most adherent) to 120 (least adherent). Chronic pain was measured using the FPS‐R and was dichotomized as high for FPS‐R scores ≥4 and low for <4. Logistic regression models were constructed to assess factors associated with having high (vs. low) chronic pain. Of 80 AYA respondents (79 men), most had severe disease (91%), infused prophylactically (86%) and had haemophilia A (91%). Fifty‐one per cent were aged 13–17 and most were white (76%), non‐Hispanic (88%) and never married (93%). Chronic pain was reported as high for 35% of respondents. Mean VERITAS‐Pro scores for those with high and low chronic pain were 53.6 ± 12.3 vs. 47.4 ± 12.9, P = 0.05. VERITAS‐PRN scores were similar across chronic pain status. Logistic regression revealed that for each 10‐point reduction (i.e. increase in adherence) in the combined VERITAS (Pro and PRN) and VERITAS‐Pro scores there was a 35% (OR = 0.65; 95%CI = 0.44, 0.96; P = 0.03) and 39% (OR = 0.61; 95%CI = 0.39, 0.96; P = 0.03) reduction in odds of having high chronic pain respectively. Among AYA PWHs, better adherence was associated with significantly lower odds of having high chronic pain. Moreover, non‐whites were >4 times as likely as whites to report high chronic pain.     

VERITAS‐Pro: a new measure of adherence to prophylactic regimens in haemophilia

Summary. Prophylactic treatment is recommended for severe haemophilia. Non‐adherence to a prophylactic regimen can limit treatment effectiveness and compromise outcomes. The aim of this study is to validate a new prophylactic treatment adherence scale entitled Validated Hemophilia Regimen Treatment Adherence Scale – Prophylaxis (VERITAS‐Pro), a self‐/parent‐report questionnaire consisting of 24 questions on six (four‐item) subscales (Time, Dose, Plan, Remember, Skip, Communicate) that takes approximately 10 min to complete and is currently available in English only. Participants were recruited to complete the VERITAS‐Pro for validation and reliability analysis; and observers were recruited for inter‐rater reliability analysis. Validation measures included subjective adherence ratings from participants and providers and the total number of recommended infusions administered as obtained from infusion logs. Data were evaluated for the entire sample and for parent‐report and self‐report subsamples. The study sample included 67 males, 53 (79.1%) diagnosed with severe FVIII deficiency. Internal consistency for the total VERITAS‐Pro score and all subscales was good to excellent; test‐retest reliability correlations were very strong. Validation measures were strongly correlated with VERITAS‐Pro scores. The VERITAS‐Pro is a reliable and valid measure of adherence to prophylactic treatment of haemophilia. The VERITAS‐Pro has greater utility than a global or informal rating of adherence because it represents a quantified and validated measure of adherence from the patient’s perspective and it divides adherence into specific areas, allowing insight into particular issues underlying non‐adherence. This tool may increase sensitivity to adherence problems and allow more targeted interventions to enhance adherence.     

Improvement in health‐related quality of life with recombinant factor IX prophylaxis in severe or moderately severe haemophilia B patients: results from the BAX326 Pivotal Study

Little is known about the health‐related quality of life (HRQoL) burden of haemophilia B. The aim of this study was to assess HRQoL burden of haemophilia B, the benefit of recombinant factor IX (rFIX) prophylaxis and the HRQoL benefit of achieving a zero annual bleed rate. Subjects receiving rFIX (BAX326) prophylaxis or on‐demand completed the SF‐36 survey. Baseline SF‐36 scores were compared to the general US population scores to understand the HRQoL burden. Changes in SF‐36 scores between baseline and follow‐up were tested using t‐tests. Subgroup analysis was conducted to examine SF‐36 change among subjects who switched to BAX326 prophylaxis. SF‐36 scores were also compared between those with zero bleeds and those who bled during the study. Compared to the US norms, subjects reported lower average scores in all physical and several mental HRQoL domains. At follow‐up, prophylaxis subjects reported statistically significant and clinically meaningful improvements in overall physical HRQoL, as measured by the Physical Component Score (PCS) (mean change 2.60, P = 0.019), Bodily Pain (BP) (3.45, P = 0.015) and Role Physical (RP) domains (3.47, P = 0.016). Subjects who switched to prophylaxis from intermittent prophylaxis or on‐demand experienced more pronounced improvements not only in the PCS (3.21, P = 0.014), BP (3.71, P = 0.026), RP (4.43, P = 0.008) but also in Vitality (3.71, P = 0.04), Social Functioning (5.06, P = 0.002) and General Health domains (3.40, P = 0.009). Subjects achieving zero bleeds reported lower BP (P = 0.038). Prophylaxis with BAX326 significantly improved HRQoL in patients with moderately severe or severe haemophilia B by reducing bleeds.     

Adherence to prophylaxis and bleeding outcome in haemophilia: a multicentre study

Prevention of bleeding and joint damage in severe haemophilia is dependent on adherence to prophylactic replacement therapy. The aim of this study was to assess adherence to prophylaxis, including associations with age, bleeding and clotting factor consumption (CFC). In three Dutch haemophilia centres, semi‐structured interviews about adherence to prophylaxis in the previous 2 weeks were conducted with patients or parents of a child with haemophilia. Patients were classified, according to pre‐specified definitions, as adherent, sub‐optimally adherent or non‐adherent based on missing, timing, and dose of infusions. Association of annual bleeding rates, mean CFC, person performing the infusion (parents verus patients) with adherence categories were analysed. Overall, 241 patients with haemophilia using prophylaxis were studied. Parents were more adherent (66%; n = 48/73) than patients (43%; n = 72/168). Sub‐optimal adherence occurred in 29% of parents and 37% of patients and was characterized by changes in timing of infusion (mostly from morning to evening), while missing <6% of infusions. Non‐adherence occurred less often: in 5% of parents and 20% of patients. Reduced adherence was associated with lower CFC, but not with joint bleeding. In conclusion, non‐adherence in haemophilia was relatively rare, yet 1/3 of patients struggled to administer prophylaxis at the appropriate time of day.     

Health‐related quality of life in patients with haemophilia and inhibitors on prophylaxis with anti‐inhibitor complex concentrate: results from the Pro‐FEIBA study

Patients with haemophilia A and inhibitors are at high risk for severe bleeding, progression of joint disease and deterioration of health‐related quality of life (HRQoL). To determine the impact of prophylaxis with an activated prothrombin complex concentrate (aPCC) on HRQoL, HRQoL was assessed using the Short‐Form (SF)‐36 Health Survey and the EQ‐5D questionnaire in subjects ≥14 years participating in a prospective, randomized, crossover study comparing 6 months of aPCC prophylaxis with 6 months of on‐demand therapy. Eighteen of 19 patients completed the survey or questionnaire before and after the on‐demand therapy and prophylaxis periods. A general trend towards improved HRQoL after prophylaxis was observed for the 18 evaluable patients in all SF‐36 dimensions except for vitality/energy and physical functioning. After prophylaxis, ‘good responders,’ defined as patients experiencing ≥50% reduction in bleeding, exhibited statistically and clinically significant differences in the physical component score (P = 0.021), role – physical (P = 0.042), bodily pain (P = 0.015), and social functioning (P = 0.036). Similarly, the EQ‐5D health profile showed a trend towards improvement after prophylaxis in all evaluable patients. Among the good responders, improvements did not differ from those observed after on‐demand treatment. EQ visual analogue scale values were slightly improved following prophylaxis for all evaluable patients and the EQ‐5D utility index improved in the good responders only. During prophylaxis, patients missed significantly fewer days from school or work because of bleeding than during on‐demand treatment (P = 0.01). In conclusion, by significantly reducing bleeding frequency in good responders, aPCC prophylaxis improved HRQoL compared with on‐demand treatment.     

Presentation and management of acute coronary syndromes among adult persons with haemophilia: results of an international,retrospective, 10‐year survey

Sparse data are available on presentation and management of acute coronary syndromes (ACS), including unstable angina and non‐ST‐ and ST‐elevation myocardial infarction, among persons with haemophilia (PWH). The aim of this study was to determine demographics, bleeding disorder characteristics, cardiovascular risk factors (CRFs), interventions, haemostatic protocol, revascularization outcomes and complications among PWH with ACS. Members of an international consortium comprising >2000 adult PWH retrospectively completed case report forms for episodes of ACS in a >10‐year follow‐up period (2003–2013). Twenty ACS episodes occurred among 19 patients [rate, 0.8% (95% CI 0.4, 1.2)]. Seven patients (37%) were aged <50 years; 10 (53%) had ≥3 CRFs. In 5/20 episodes (25%), the initial ACS management protocol was altered because of the bleeding disorder. None of the eight patients with severe haemophilia underwent coronary artery bypass grafting (CABG), compared with 54.5% of patients with non‐severe disease (P = 0.02). Revascularization with percutaneous coronary intervention (PCI) or CABG was rated successful in 13/13 cases, with no excessive bleeding during initial management. During chronic exposure to antiplatelet agents, secondary haemophilia prophylaxis was more prevalent in patients with severe haemophilia compared with non‐severe haemophilia (85.7% vs. 30%, P = 0.05). No ACS‐related deaths occurred during initial management, but one patient with severe haemophilia A died of undetermined cause 36 months after the ACS event while on aspirin therapy. ACS occurs even among relatively younger PWH, typically in association with multiple CRFs. Revascularization with PCI/CABG is feasible, and antiplatelet agents plus secondary prophylaxis appears to be well tolerated in selected PWH with ACS.     

Physical activity and health outcomes in persons with haemophilia B

Regular participation in physical activity helps to prevent damage and maintain joint health in persons with haemophilia. This study describes self‐reported physical activity participation among a sample of people with haemophilia B in the US and measures its association with health‐related quality of life (HRQoL). Data on 135 participants aged 5–64 years were abstracted from Hemophilia Utilization Group Study Part Vb. The International Physical Activity Questionnaire assessed physical activity among participants aged 15–64 years, and the Children's Physical Activity Questionnaire abstracted from the Canadian Community Health Survey was used for participants aged 5–14 years. SF‐12 was used to measure HRQoL and the EuroQol (EQ‐5D‐3L) was used to measure health status for participants older than 18 years of age. PedsQL was used to measure HRQoL in children aged 5–18 years. Sixty‐two percent of participants in the 15–64 year‐old age cohort reported a high level of physical activity, 29% reported moderate activity and 9% reported low activity. For children aged 5–14 years, 79% reported participating in physical activity for at least 4 days over a typical week. Based on the 2008 Physical Activity Guidelines for Americans, 79% of adults achieved the recommended physical activity level. Multivariable regression models indicated that adults who engaged in a high level of physical activity reported EQ‐5D Visual Analogue Scale (VAS) scores that were 11.7 (P = 0.0726) points greater than those who engaged in moderate/low activity, indicating better health outcomes. Among children, no statistically significant differences in health outcomes were found between high and moderate or low activity groups.     

The burden of bleeding in haemophilia: is one bleed too many?

Joint bleeding is the hallmark of haemophilia. Increasingly, the pain, restricted movement and anxiety provoked by even a single haemarthrosis are concerns for patients, families and treating physicians. The aims of this study were to determine whether the current paradigm for prophylaxis requires a shift in focus from reducing the frequency of bleeding episodes to a goal of zero bleeding and to review and discuss the published data from in vitro and animal experiments and clinical studies in patients with haemophilia that describe the impact of joint bleeding. More than two to three bleeding into the same joint may cause irreversible and progressive structural damage that compromise health‐related quality of life (HRQoL). A goal of zero bleeding episodes – or as close to zero as possible – is key to enhancing joint health and HRQoL in children and adults with haemophilia. Achieving this goal requires individualized, outcome‐based, multidisciplinary care to maximize prophylactic efficacy without increasing overall health care costs.     

Bone density and health‐related quality of life in adult patients with severe haemophilia

Summary. Severe haemophilia and reduced bone density can negatively influence perception of patient’s health‐related quality of life (HRQoL), especially considering future aspects, the risk of losing independence or pain suffering. The aim of this study was to assess levels of HRQoL in severe haemophilia patients and to compare HRQoL to those of the general population as well as to determine whether reduced bone density is correlated to the perceived HRQoL. Patients were divided into two groups based on timing of being treated with prophylaxis: Group A (started prophylaxis at age of ≤3 years; n = 22); Group B (at age of >3 years; n = 15). The bone mineral density (BMD g cm^?2) of different measured sites was measured by dual energy X‐ray absorptiometry (DXA). HRQoL was assessed using SF‐36 questionnaire. Group A have mean BMD T‐score >?1.0 (i.e. normal score) at all measured sites, and have almost similar scores in the SF‐36 domains compared with the reference population. Group B have mean BMD T‐score ?1.0 at lumbar spine and total body, and their scores in the SF‐36 domains were lower compared with the reference population. Moreover, significant correlations were found between BMD at femoral neck and total body with physical domains. With adequate long‐term prophylaxis since early childhood, adult patients with haemophilia report a comparable BMD and HRQoL to the Swedish reference population. Reduced BMD in group B correlated with impaired physical health, which underscores the importance of early onset of adequate prophylactic treatment.     

Safe switching from a pdFIX (Immunine®) to a rFIX (Bax326)

The ability to switch between coagulation factors safely is of common interest to haemophilia patients and treating physicians. This is the first formal prospective comparative evaluation of safety, efficacy and incremental recovery of a plasma‐derived FIX (pdFIX) and a recombinant FIX (rFIX) in the same haemophilia B patients following a switch from pdFIX Immunine^® to a recently developed rFIX Bax326 product. Patients (aged <65 years) who completed a pretreatment study which prospectively documented the exposure to Immunine^® and monitored FIX inhibitors while receiving prophylactic treatment were transitioned into pivotal (patients aged 12–65 years) and paediatric (patients aged <12 years) clinical studies investigating prophylaxis and treatment of bleeding episodes with Bax326. None of the 44 patients developed inhibitory or specific binding anti‐FIX antibodies during the course of the studies. A total of 38 unrelated adverse events (AEs) were occurred in 20/44 (45.5%) subjects during the Immunine^® study. Following a switch to Bax326, 51 AEs were reported in 25/44 (56.8%) subjects. The incidence of AEs related to Bax326 treatment (two episodes of dysgeusia in one patient) was low (2.3%); there were no serious adverse reactions. The comparison between Immunine^® and Bax326 demonstrated analogous haemostatic characteristics and annualized bleeding rates. Overall, there is direct evidence indicating a safe and clinically effective transition from a pdFIX (Immunine^®) to a newly developed rFIX (Bax326¹) for prophylaxis and treatment of bleeding in previously treated patients of all age cohorts with severe or moderately severe haemophilia B.     

Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS-Va)

Summary. This study describes health‐related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self‐reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2‐year cohort study, we collected baseline HRQoL using the SF‐12 (adults) and PedsQL (children), along with self‐ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self‐reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self‐reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.     

Treatment trends for haemophilia A and haemophilia B in the United States: results from the 2010 practice patterns survey

Frequent evaluation of haemophilia treatment is necessary to improve patient care. The 2010 Practice Patterns Survey (PPS) investigated current trends in haemophilia treatment in the United States, as reported by nurses. The aim was to document practice patterns for haemophilia A and haemophilia B Survey questionnaires were sent to nurses at haemophilia treatment centres (HTCs) across the United States. Seventy-one of 126 HTCs (56%) responded to the survey. Factor dosage across treatment modalities ranged from 20 to 50 IU kg(-1) for severe haemophilia A. Dosage for severe haemophilia B was more variable (<40 to >100 IU kg(-1)). On-demand dosing regimens were inconsistent for haemophilia A and more so for haemophilia B. Rates of adherence to prescribed treatment were similar for both haemophilia types (～80%). The main barrier to adherence was identified as inconvenience. More bleeding episodes occurred in adults (16.6 bleeding episodes per year) with severe haemophilia A than in younger patients (11.3 bleeding episodes per year) before switching patients to prophylaxis. For both haemophilia types, most patients who switched from prophylaxis to on-demand treatment were aged 13-24 years; these patients also had the lowest adherence (60-71%). More paediatric patients with severe haemophilia A and inhibitors (53%) received prophylactic bypassing therapy than their haemophilia B counterparts (38%). Adults with severe haemophilia A faced challenges in relation to co-morbidities and long-term care. This PPS provides insights into previously unexplored aspects of haemophilia care that will serve to increase awareness and promote discussion of current issues affecting haemophilia patient care.     

Self‐monitoring has potential for home exercise programmes in patients with haemophilia

Haemophiliacs who have had to keep a physically inactive lifestyle due to bleeding during childhood are likely to have little motivation for exercise. The purpose of this study is to clarify the effectiveness of the self‐monitoring of home exercise for haemophiliacs. A randomized controlled trial was conducted with intervention over 8 weeks at four hospitals in Japan. Subjects included 32 male outpatients aged 26–64 years without an inhibitor who were randomly allocated to a self‐monitoring group and a control group. Individual exercise guidance with physical activity for improvement of their knee functions was given to both groups. The self‐monitoring materials included an activity monitor and a feedback system so that the self‐monitoring group could send feedback via the Internet and cellular phone. The self‐monitoring was performed by checking exercise adherence and physical activity levels, bleeding history and injection of a coagulation factor. Both groups showed significant improvements in exercise adherence (P < 0.001) and physical function such as the strength of knee extension (P < 0.001), range of knee extension (P < 0.001), range of ankle dorsiflexion (P < 0.01), a modified Functional Reach (P < 0.05) and 10 metre gait time (P < 0.01). In particular, improvements in exercise adherence (P < 0.05), self‐efficacy (P < 0.05), and strength of knee extension (P < 0.05) were significant in the self‐monitoring group compared with those in the control group. No increase in bleeding frequency and pain scale was noted. The self‐monitoring of home exercise for haemophilic patients is useful for the improvement of exercise adherence, self‐efficacy and knee extension strength.     

Impact of timing of prophylaxis commencement,F8 genotype and age on factor consumption and health-related quality of life in patients with severe haemophilia A

Introduction

The timing of prophylaxis and F8 genotype can impact treatment outcomes in adults with severe haemophilia A (HA).

Aim

To investigate how F8 genotype, timing, and type of prophylaxis influence arthropathy, bleeding rates, factor consumption and health-related quality of life (HRQoL).

Methods

Thirty-eight patients with severe HA were enrolled. Bleeding events were recorded retrospectively during median 12.5 months. F8 gene variants were classified as null or non-null. Joint health and HRQoL were assessed with HJHS and EQ-5D-5L, respectively.

Results

The median age at prophylaxis start was 1.25 years in the primary prophylaxis group (N = 15, median age 26 years) and 31.5 years in the secondary group (N = 22, 45 years), respectively. There were significant differences in the medians of HJHS (4 vs. 20, p < .001), EQ-5D-5L index (0.9647 vs. 0.904, p = .022), EQ VAS (87 vs. 75, p = .01) and FVIII consumption (3883 vs. 2737 IU/kg/year, p = .02), between the primary and secondary groups, respectively. Median annualized bleeding rate (ABR) was 0 for both groups. Twenty-five null and thirteen non-null F8 gene variants were identified. In the secondary prophylaxis group, lower median FVIII consumption (1926 vs. 3370 IU/kg/year) was shown for non-null compared to null variants, respectively, with similar ABR and HJHS.

Conclusion

Delayed prophylaxis start with intermediate dose intensity prevents bleeds but at a cost of more arthropathy and reduced HRQoL, compared to higher intensity primary prophylaxis. Non-null F8 genotype may allow lower factor consumption with similar HJHS and bleeding rates, compared to null genotype.     

Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial

A newly developed recombinant factor IX (BAX326¹) was investigated for prophylactic use in paediatric patients aged <12 years with severe (FIX level <1%) or moderately severe (FIX level 1–2%) haemophilia B. The aim of this prospective clinical trial was to assess the safety, haemostatic efficacy and pharmacokinetic profile of BAX326 in previously treated paediatric patients. BAX326 was administered as prophylaxis twice a week for a period of 6 months, and on demand for treatment of bleeds. Safety was assessed by the occurrence of related AEs, thrombotic events and immunologic assessments. Efficacy was evaluated by annualized bleeding rate (ABR), and by treatment response rating (excellent, good, fair, none). PK was assessed over 72 h. None of the 23 treated paediatric subjects had treatment‐related SAEs or AEs. There were no thrombotic events, inhibitory or specific binding antibodies against FIX, rFurin or CHO protein. Twenty‐six bleeds (19 non‐joint vs. 7 joint bleeds) occurred (mean ABR 2.7 ± 3.14, median 2.0), of which 23 were injury‐related. Twenty subjects (87%) did not experience any bleeds of spontaneous aetiology. Haemostatic efficacy of BAX326 was excellent or good for >96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1–2 infusions. Longer T_1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B.     

Influence of medical insurance schemes and charity assistance projects on regular prophylaxis treatment of the boys with severe haemophilia A in China

Objective

To explore the influence of medical insurance policy and charity assistance projects on the uptake and discontinuation of regular prophylaxis treatment in Chinese severe haemophilia A children.

Methodology

This retrospective study was conducted on children with severe haemophilia A, who received FVIII prophylaxis treatment at 12 haemophilia centres in China from 1 November 2007 to 31 May 2013.

Results

The average duration of prophylaxis treatment received by haemophilia children significantly increased from 16.7 weeks in 2008 to 32.8 weeks in 2012 (P < .001). The main reason for prophylaxis acceptance included dissatisfaction with previous “on‐demand” regimens, availability of improved local medical insurance policies and patient/family awareness of haemophilia. The main reason for subsequent discontinuation of prophylaxis was economic instability. The upper limit of insurance was up to RMB 150 000/y (~USD: 22 000/y) for 80.1% of the insured patients and would be sufficient to cover the continuous low‐dose prophylaxis regimen. However, for many patients the burden of out‐of‐pocket copayment cost represented a risk for poor adherence to regular prophylaxis. In about two third of the patients, the annual out‐of‐pocket copayment cost amounted to >50% of their average annual disposable income. Many patients therefore required assistance from the charity assistance projects, but nonadherence remained prevalent.

Conclusion

Medical insurance policy and charity assistance projects helped haemophilia children to accept and continue prophylaxis regimens. It was the proportion of the out‐of‐pocket copayment cost rather than the upper limit of insurance reimbursement that restricted long‐term regular low‐dose prophylaxis in China.     

Prophylaxis with FEIBA in paediatric patients with haemophilia A and inhibitors

The benefits shown with factor VIII (FVIII) prophylaxis relating to joint health and quality of life (QoL) provide the rationale for FEIBA prophylaxis in haemophilia A patients with persistent FVIII inhibitors. FEIBA has previously shown efficacy in preventing bleeds in inhibitor patients who failed to respond to, or were ineligible for immune tolerance induction (ITI). The study examined the outcome of paediatric patients undergoing long‐term FEIBA prophylaxis. A retrospective chart review included severe haemophilia A patients with persistent inhibitors aged ≤13 years at the start of FEIBA prophylaxis. Baseline characteristics captured dose, frequency of prophylaxis, history of inhibitor development, including baseline titre, historical peak titre and history of ITI. Outcome measurements included annual bleed rate before and during FEIBA prophylaxis, joint status and school days missed. Sixteen cases of FEIBA prophylaxis from two centres are presented. The mean age of subjects at prophylaxis initiation was 7.5 ± 3.6 years and median baseline inhibitor titre was 23 (range 3.1–170) BU. Prior to prophylaxis initiation, median annual joint bleeds among all patients was 4 (0–48), which dropped significantly after the first year of prophylaxis, to a median annual joint bleed rate of 1 (0–7; P = 0.0179). Subsequent years (median = 9) of prophylaxis therapy demonstrated similarly low annual joint bleed rates. There were no life‐threatening bleeds, no viral seroconversions or thrombotic events during FEIBA prophylaxis treatment. FEIBA prophylaxis was effective for preventing joint bleeds and subsequent joint damage, delaying arthropathy and improving outcomes in children with haemophilia A and inhibitors to FVIII, who failed or were ineligible for ITI.