Pharmacokinetics,efficacy and safety of BAX326, a novel recombinant factor IX: a prospective,controlled, multicentre phase I/III study in previously treated patients with severe (FIX level <1%) or moderately severe (FIX level ≤2%) haemophilia B

BAX326 is a recombinant factor IX (rFIX; nonacog gamma) manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps (solvent/detergent treatment and 15 nm nanofiltration). The aim of this prospective trial was to investigate the pharmacokinetics, haemostatic efficacy and safety of BAX326 in previously treated patients aged 12–65 years with severe or moderately severe haemophilia B. BAX326 was safe and well tolerated in all 73 treated subjects; adverse events considered related to treatment (2.7% incidence, all non‐serious) were transient and mild, and no hypersensitivity reactions, inhibitor formation or thrombotic events were observed. Pharmacokinetic (PK) equivalence (n = 28) between BAX326 and a licensed rFIX was confirmed in terms of the ratio of geometric mean AUC_0–72 h per dose. Twice‐weekly prophylaxis [mean duration 6.2 (±0.7) months; 1.8 (±0.1) infusions per week, 49.5 (±4.8) IU kg^?1 per infusion] was effective in preventing bleeding episodes, with a significantly lower (79%, P < 0.001) annualized bleed rate (4.2) compared to an on‐demand treatment in a historical control group (20.0); 24 of 56 subjects on prophylaxis (43%) did not bleed throughout the study observation period. Of 249 total acute bleeds, 211 (84.7%) were controlled with one to two infusions of BAX326. Haemostatic efficacy at resolution of bleed was rated excellent or good in 96.0% of all treated bleeding episodes. The results of this study indicate that BAX326 is safe and efficacious in treating bleeds and routine prophylaxis in patients aged 12 years and older with haemophilia B.     

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.     

Adherence to prophylaxis is associated with better outcomes in moderate and severe haemophilia: results of a patient survey

Severe haemophilia is associated with bleeding into joints and development of arthropathy. Prophylactic treatment with infusion of replacement clotting factor is known to prevent bleeding, preserve joint functioning and result in higher health‐related quality of life (HRQoL) than episodic treatment; however, adhering to standard prophylaxis schedules can be difficult, and little is known about the relationship between adherence to prophylactic treatment and outcomes. The aim of this study was to assess the relationship between self‐reported adherence to prophylaxis and health outcomes, including HRQoL and bleeding episodes. Adults with haemophilia (n = 55) and caregivers of children with haemophilia (n = 55) in Australia, Canada, and the United States completed an online questionnaire which included measures of HRQoL (SF‐12v2 for adults and SF‐10 for caregivers of children), self‐reported bleeding episodes, and the VERITAS‐Pro measure of adherence to prophylaxis in haemophilia. Regression analysis was used to test the association between VERITAS‐Pro total score and outcomes. Poorer adherence (higher VERITAS‐Pro scores) was associated with a greater number of self‐reported bleeding episodes in the past year among adults (p < 0.01), more days of work/school missed among paediatric patients (p < 0.01), and lower physical health status scores among paediatric patients (p < 0.05). This study highlights the benefits of adherence to prophylaxis among those with severe haemophilia and provides evidence for the utility of the VERITAS‐Pro by demonstrating a relationship between adherence and outcomes.     

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.     

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.     

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.     

Efficacy and safety of a recombinant factor IX (Bax326) in previously treated patients with severe or moderately severe haemophilia B undergoing surgical or other invasive procedures: a prospective,open‐label,uncontrolled, multicentre,phase III study

Haemostatic management of haemophilia B patients undergoing surgery is critical to patient safety. The aim of this ongoing prospective trial was to investigate the haemostatic efficacy and safety of a recombinant factor IX (rFIX) (Bax326) ¹ in previously treated subjects (12–65 years, without history of FIX inhibitors) with severe or moderately severe haemophilia B, undergoing surgical, dental or other invasive procedures. Haemostatic efficacy was assessed according to a predefined scale. Blood loss was compared to the average and maximum blood loss predicted preoperatively. Haemostatic FIX levels were achieved peri‐ and postoperatively in 100% of subjects (n = 14). Haemostasis was ‘excellent’ intraoperatively in all patients and postoperatively in those without a drain, and ‘excellent’ or ‘good’ at the time of drain removal and day of discharge in those with a drain employed. Following the initial dose, the mean FIX activity level rose from 6.55% to 107.58% for major surgeries and from 3.60% to 81.4% for minor surgeries. Actual vs. predicted blood loss matched predicted intraoperative blood loss but was equal to or higher than (but less than 150%) the maximum predicted postoperative blood loss reflecting the severity of procedure and FIX requirements. There were no related adverse events, severe allergic reactions or thrombotic events. There was no evidence that BAX326 increased the risk of inhibitor or binding antibody development to FIX. BAX326 was safe and effective for peri‐operative management of 14 subjects with severe and moderately severe haemophilia B.     

A longitudinal evaluation of health‐related quality of life in patients with AL amyloidosis: associations with health outcomes over time

Light chain (AL) amyloidosis is a rare disease associated with significant, irreversible organ dysfunction and high case fatality. An observational study was conducted to assess health‐related quality of life (HRQoL) in patients treated for AL amyloidosis between 1994 and 2014 with both high dose melphalan and stem cell transplantation (HDM/SCT) or non‐SCT chemotherapy regimens. The SF‐36v1^® Health Survey (SF‐36) was administered to assess HRQoL during clinic visits. Analysis of variance was used to compare pre‐ and post‐treatment HRQoL within each treatment group to an age‐ and gender‐adjusted general population (GP) normative sample. Cox proportional hazard models were fit to examine associations between pre‐treatment levels of HRQoL and mortality within 1 and 5 years after initiating specific treatment regimens (HDM/SCT: n = 402; non‐SCT chemotherapy regimens: n = 172). Among patients who received HDM/SCT, there were significant improvements following treatment in vitality, social functioning, role‐emotional and mental health. Worse pre‐treatment SF‐36 physical component scores were associated with a greater risk of mortality in both treatment groups and follow‐up periods (P ≤ 0·005 for both). [Correction added on 20 October 2017, after first online publication: This P value has been corrected]. Using HRQoL assessments in every physician visit or treatment may provide valuable insights for treating rare conditions like AL amyloidosis.     

Long‐acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B‐LONG study

In the phase 3 B‐LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half‐life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately‐severe to severe haemophilia B. In this B‐LONG sub‐analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator‐determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, ~2 weeks–12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85·7%), haemostasis from the pre‐surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R² = 0·9586, P < 0·001) between observed and population pharmacokinetic model‐predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.     

Coping in adult patients with severe haemophilia

An adequate use of coping strategies could help patients to deal with disease‐related stress. The study aim was to explore coping behaviour in adult patients with severe haemophilia and its possible determinants. Coping was assessed through three basic dimensions (task‐oriented, emotion‐oriented and avoidance coping), using the short version of the Coping Inventory for Stressful Situations (CISS‐21). Patients' scores were compared with Dutch working men (N = 374), according to three categories: low use (<P25 of normal), average use (P25–P75) and high use (>P75). Determinants were measured using questionnaires on activities (Haemophilia Activities List), participation (Impact on Participation and Autonomy Questionnaire), physical functioning [physical component of the Dutch Arthritis Impact Measurement Scales‐2 (D‐AIMS2)] and socio‐psychological health (psychological component of the D‐AIMS2). In total, 86 adults with severe haemophilia (FVIII/IX<1%) were included. The median age was 38 years (range: 18–68) with 85% affected with haemophilia A and 75% using prophylaxis. Patients with haemophilia used task‐oriented coping as frequently as the control group (P = 0.13); but used significantly less emotion‐oriented coping (57% vs. 25%, P < 0.05) and avoidance coping (P < 0.05). Emotion‐oriented coping showed a strong correlation with socio‐psychological health (r = 0.67) and weak correlations with participation (r = 0.32) and social interaction (r = 0.29). Other associations of coping strategies with patient characteristics of health status could not be demonstrated. Overall, patients predominantly used the task‐oriented approach to deal with their disease; the use of this strategy was comparable to the control group. Having a poor psychological health, less social interaction and/or less participation in daily life was associated with an increased use of emotion‐oriented coping.     

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.     

Patterns of tertiary prophylaxis in Canadian adults with severe and moderately severe haemophilia B

From a young age patients with severe and moderately severe FIX deficiency (haemophilia B) can experience spontaneous or traumatic bleeding and joint destruction may result. The use of coagulation factor IX concentrate to prevent anticipated bleeding, as primary or secondary prophylaxis, has become a common and recommended practice in children. The current practice of using tertiary prophylaxis, in the presence of established joint arthropathy, in adults with haemophilia B is not well characterized. This observational study was conducted to gain a better understanding of the recent Canadian experience with tertiary prophylaxis in adults with severe and moderately severe haemophilia B. Data were collected from all eligible adult (≥ 18 years of age) males with baseline FIX:C ≤ 2% from seven Canadian Hemophilia Treatment centres over a 2‐year observation period from 2009 to 2011. Thirty‐four per cent of the 67 subjects with moderately severe haemophilia B were exposed to prophylaxis with the majority as continuous prophylaxis (≥45 weeks year^‐1). The severe subgroup (FIX:C < 1%) demonstrated a 52% exposure rate. None had primary prophylaxis exposure in childhood. Eighty‐one per cent used once or twice weekly infusion regimens and reported a median annual bleeding rate of five bleeds per year versus four bleeds per year for those using on‐demand treatment. Annual median factor utilization for all subjects using prophylaxis was 196 283 U year^‐1 compared to 46 361 U year^‐1 for on demand. Approximately 50% of adults with severe haemophilia B are using continuous tertiary prophylaxis in Canada, a practice likely to increase which warrants further study.     

Improved joint health in subjects with severe haemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein

Introduction

Joint arthropathy is the long‐term consequence of joint bleeding in people with severe haemophilia.

Aim

This study assessed change in joint health over time in subjects receiving recombinant factor VIII Fc fusion protein (rFVIIIFc) prophylaxis.

Methods

ALONG is the phase 3 pivotal study in which the benefit of rFVIIIFc as a prophylactic treatment for bleeding control was shown in previously treated severe haemophilia patients ≥12 years of age (arm 1: 25‐65 IU/kg every 3‐5 days, arm 2: 65 IU/kg weekly and arm 3: episodic). After completing ALONG, subjects had the option to enrol into the extension study (ASPIRE). This interim, post hoc analysis assessed changes in joint health over ~2.8 years in these patients.

Results

Forty‐seven subjects had modified Haemophilia Joint Health Score (mHJHS) data at A‐LONG baseline, ASPIRE baseline and ASPIRE Year 1 and Year 2. Compared with A‐LONG baseline (23.4), mean improvement at ASPIRE Year 2 was ?4.1 (95% confidence interval [CI], ?6.5, ?1.8; P = .001). Regardless of prestudy treatment regimen, subjects showed continuous improvement in mHJHS from A‐LONG baseline through ASPIRE Year 2 (prestudy prophylaxis: ?2.4, P = .09; prestudy episodic treatment: ?7.2, P = .003). Benefits were seen in subjects with target joints (?5.6, P = .005) as well as those with severe arthropathy (?8.8, P = .02). The mHJHS components with the greatest improvement at ASPIRE Year 2 were swelling (?1.4, P = .008), range of motion (?1.1, P = .03) and strength (?0.8, P = .04).

Conclusions

Prophylaxis with rFVIIIFc may improve joint health over time regardless of prestudy prophylaxis or episodic treatment regimens.     

Lifelong prophylaxis in a large cohort of adult patients with severe haemophilia: a beneficial effect on orthopaedic outcome and quality of life

Background: In the 1950s, Sweden initiated prophylaxis as a lifelong treatment for haemophilia. It was the first country to do so. Objectives: To describe and evaluate dosing and outcome of prophylactic treatment in a large cohort of adult people with severe haemophilia who have been using prophylaxis most of their lives. Methods: Eighty‐one patients born between 1932 and1992 were divided into two groups (Group A started prophylaxis at the age of ≤ 3 yr; Group B at three or more years of age) and evaluated retrospectively. Outcome was evaluated using the Hemophilia Joint Health Score (HJHS) and SF‐36, a measure of quality of life. Results: The median number of joint bleeds per year was 0 in both study groups; however, the annual number of joint bleeds during the final 3 yr of observation was higher in group B than in group A (P < 0.006). Twenty‐five of 30 patients in group A and 27/51 patients in group B had no joint bleeds in that period. Group A had significantly better joint outcomes than group B. Patients in group A experienced better physical and social health than those in group B. Conclusions: This follow‐up has provided for the first time more extensive and detailed information regarding the practice of prophylactic treatment in a large cohort of adults with severe haemophilia. The present study confirms that early start of prophylaxis continuing throughout the lifespan has been successful in virtually eliminating joint bleeds, preserving a close to normal joint status, and keeping patients healthy and able to live normal lives.     

The impact of haemarthropathy on the QoL of Korean severe haemophilia A patients: the critical level of haemarthropathy for the QoL

The minimum goal of secondary prophylaxis may be to delay the progression of haemarthropathy below a critical level over which it has a great impact on the QoL of haemophilia patients. However, the critical level of haemarthropathy may be different across countries. For these reasons, the impact of haemarthropathy on the QoL in Korean haemophilia A patients was investigated. Depending on observed Pettersson scores of 27 severe haemophilia A patients, they were divided into three groups, P (Pettersson score) ≤10, P11~19 and P ≥ 20 groups. The QoL of each patient, assessed by the SF36, was compared between the groups. In addition, the changes in the QoL of the patients were observed according to the changes of Pettersson scores to find out the critical level of arthropathy. None of the scores of the SF36 scales were different between the P ≤ 10 and P11~19 groups. In contrast, the scores of PF and MH scales were significantly different between the P11~19 and P ≥ 20 groups. When changes in the scores of each scale in the SF36 were observed according to changes in Pettersson scores, the average P score of 13.0 ± 2.7 was thought to be the critical level of haemarthropathy because above that level, haemarthropathy and physical and mental health of the patients rapidly deteriorated. The progression of haemarthropathy to the critical level should be delayed as long as possible to prevent or to delay a rapid deterioration of the QoL of Korean patients with haemophilia.     

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.     

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.     

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.     

Physical and mental quality of life in adult patients with haemophilia in Belgium: the impact of financial issues

In Belgium, where haemophilia affects approximately 1:7000 people (2011), data on patients' quality of life (QoL) is scarce. This project aims to assess physical and mental QoL (P‐QoL and M‐QoL) simultaneously, and to analyse the influence of different variables on these two aspects of QoL. After Ethics Committee approval, we contacted 84 adult haemophilia A (HA) and haemophilia B (HB) patients, without current inhibitors, on replacement therapy (on‐demand or secondary prophylaxis), regularly followed up at our comprehensive treatment centre. Seventy‐one (n = 59 HA, n = 12 HB) replied to our questionnaire, which included the SF36v2 QoL assessment forms. We analysed two groups of variables: one including variables previously associated with decreased QoL, and another including variables with unclear impact on QoL (e.g. patients' understanding of haemophilia‐related issues, economical concerns). In our population (mean ± SD age: 45.2 ± 14.7 years old), P‐QoL appeared more reduced than M‐QoL. P‐QoL was strongly influenced by the number of arthropathies while M‐QoL was primarily affected by patients' concern of personal costs due to haemophilia. Among this latter group, having knowledge of insurance coverage had a positive impact on M‐QoL. Scores did not depend on haemophilia type. QoL was impaired in our haemophilia patients. A simultaneous assessment of P‐QoL and M‐QoL confirmed the benefit of primary prophylaxis in P‐QoL, while originally pointing out the major burden of patients' concerns and poor understanding of haemophilia‐related economical issues on their M‐QoL. This might become a particularly challenging issue in times of financial crisis.